Compositions and related methods for delivery of liver stage antigens

Abstract

The present disclosure provides compositions (e.g., pharmaceutical compositions) for delivery of Plasmodium protein antigens, as well as related technology (e.g., components thereof and / or methods related thereto). Among other things, the present disclosure provides polyribonucleotides encoding Plasmodium protein antigens.

Description

[Background technology]

[0001] Malaria is a mosquito-borne infectious disease caused by protozoan parasites of the genus Plasmodium. According to the World Health Organization, an estimated 3.4 billion people in 92 countries are infected with the malaria parasite and are at risk of developing the disease. Summary of the Invention

[0002] The present disclosure provides pharmaceutical compositions (e.g., immunogenic compositions, e.g., vaccines) and related technology (e.g., methods) for delivering specific Plasmodium antigens (e.g., Plasmodium T cell antigens) to a subject (e.g., a patient). Plasmodium antigens may also be referred to herein as "malaria antigens" or "malarial antigens." In particular, the present disclosure provides malaria vaccine compositions and related technology (e.g., methods). The present disclosure includes the unexpected discovery that the antigens and fragments thereof disclosed herein are particularly advantageous for use in the prevention or treatment of malaria, for example, for use in the antigen constructs and / or vaccines further disclosed herein.

[0003] In some embodiments, the disclosure provides a polyribonucleotide encoding a polypeptide, wherein the polypeptide comprises one or more Plasmodium T cell antigens. In some embodiments, the one or more Plasmodium T cell antigens comprise at least two and up to 10 Plasmodium T cell antigens. In some embodiments, the encoded polypeptide comprises at least 25 and up to 1100 amino acids. In some embodiments, the encoded polypeptide comprises at least 25 and up to 500 amino acids.

[0004] In some embodiments, the polyribonucleotides disclosed herein are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (iii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (iv) an antigenic Plasmodium TRAP polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium UIS3 polypeptide fragment; (vii) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (viii) an antigenic Plasmodium LISP-1 polypeptide fragment; (ix) an antigenic Plasmodium LISP-2 polypeptide fragment, and (x) an antigenic Plasmodium LSA-3 polypeptide fragment, encoding one or more Plasmodium T cell antigens, including two or more of the following:

[0005] In some embodiments, the polyribonucleotides disclosed herein are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and (v) an antigenic Plasmodium LSAP2 polypeptide fragment, encoding one or more Plasmodium T cell antigens, including

[0006] In some embodiments, the polyribonucleotide encodes an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:15.

[0007] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-3 polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, and (viii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, encoding a polypeptide comprising one or more Plasmodium T cell antigens, including

[0008] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:18.

[0009] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (viii) an antigenic Plasmodium LISP-2 polypeptide fragment, and (ix) encoding one or more Plasmodium T cell antigens, including antigenic Plasmodium LISP-1 polypeptide fragments.

[0010] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:24.

[0011] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, and (viii) an antigenic Plasmodium LISP-1 polypeptide fragment, encoding one or more Plasmodium T cell antigens, including

[0012] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:27.

[0013] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LISP-2 polypeptide fragment, and (vii) an antigenic Plasmodium LISP-1 polypeptide fragment, encoding a polypeptide comprising one or more Plasmodium T cell antigens, including:

[0014] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:30.

[0015] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(b) polypeptide fragment, and (vii) an antigenic Plasmodium LISP-1 polypeptide fragment, encoding a polypeptide encoding one or more Plasmodium T cell antigens, including:

[0016] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:33.

[0017] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (viii) an antigenic Plasmodium LISP-2 polypeptide fragment; (ix) an antigenic Plasmodium LISP-1 polypeptide fragment, and (x) an antigenic Plasmodium LSA-3 polypeptide fragment, encoding one or more Plasmodium T cell antigens, including:

[0018] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:36.

[0019] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (ii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (iii) an antigenic Plasmodium LISP-2 polypeptide fragment; (iv) an antigenic Plasmodium LISP-1 polypeptide fragment, and (v) encoding a polypeptide comprising or consisting of one or more Plasmodium T cell antigens, including antigenic Plasmodium LSA-3 polypeptide fragments.

[0020] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:48.

[0021] In some embodiments, the polyribonucleotide is (i) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (ii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (iii) an antigenic Plasmodium LISP-2 polypeptide fragment, and (iv) an antigenic Plasmodium LISP-1 polypeptide fragment, encoding a polypeptide comprising one or more Plasmodium T cell antigens, including:

[0022] In some embodiments, the polyribonucleotide encodes a polypeptide comprising or consisting of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:45.

[0023] In some embodiments, the polyribonucleotide encodes one or more Plasmodium T cell antigens comprising an antigenic Plasmodium CSP polypeptide fragment, wherein the antigenic Plasmodium CSP polypeptide fragment comprises a Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment further comprises a Plasmodium CSP N-terminal tail region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment further comprises a Plasmodium CSP junction region.

[0024] In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:133.

[0025] In some embodiments, the one or more Plasmodium T cell antigens do not include an antigenic Plasmodium berghei CSP polypeptide fragment.

[0026] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium LSA-1(a) polypeptide fragment, wherein the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 144.

[0027] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium LSA-1(b) polypeptide fragment, wherein the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 155.

[0028] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium TRAP polypeptide fragment, wherein the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 171.

[0029] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium LSAP2 polypeptide fragment, wherein the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 198.

[0030] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium UIS3 polypeptide fragment, wherein the antigenic Plasmodium UIS3 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 212.

[0031] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, wherein the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 219.

[0032] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium LISP-1 polypeptide fragment, wherein the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 229.

[0033] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium LISP-2 polypeptide fragment, wherein the antigenic Plasmodium LISP-2 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 238.

[0034] In some embodiments, the one or more Plasmodium T cell antigens comprise an antigenic Plasmodium LSA-3 polypeptide fragment, wherein the antigenic Plasmodium LSA-3 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO: 249.

[0035] In some embodiments, the one or more Plasmodium T cell antigens each comprise one or more T cell epitopes.

[0036] In some embodiments, the polyribonucleotide encodes a polypeptide that does not include an antigenic fragment of a bacterial polypeptide. In some embodiments, the encoded polypeptide does not include an antigenic bacillus Calmette-Guerin (BCG) polypeptide fragment, and optionally, the antigenic BCG polypeptide fragment comprises an amino acid sequence according to SEQ ID NO: 461. In some embodiments, the encoded polypeptide does not include an antigenic tetanus toxin (TT) polypeptide fragment, and optionally, the antigenic TT polypeptide fragment comprises an amino acid sequence according to SEQ ID NO: 462.

[0037] In some embodiments, the one or more Plasmodium T cell antigens do not include an antigenic Plasmodium sporozoite threonine-asparagine-rich protein (STARP) polypeptide fragment, and optionally, the antigenic Plasmodium STARP polypeptide fragment comprises an amino acid sequence according to SEQ ID NO: 463.

[0038] In some embodiments, the polyribonucleotide encodes a polypeptide that further comprises an MHC class I transport signal (MITD). In some embodiments, the MITD comprises or consists of an amino acid sequence according to SEQ ID NO:479.

[0039] In some embodiments, the polyribonucleotide encodes a polypeptide that includes a secretion signal.

[0040] In some embodiments, the secretion signal comprises or consists of a Plasmodium secretion signal. In some embodiments, the Plasmodium secretion signal comprises or consists of a Plasmodium CSP secretion signal. In some embodiments, the Plasmodium CSP secretion signal comprises or consists of an amino acid sequence according to SEQ ID NO: 397.

[0041] In some embodiments, the secretory signal comprises or consists of a heterologous secretory signal. In some embodiments, the heterologous secretory signal comprises or consists of a non-human secretory signal.

[0042] In some embodiments, the heterologous secretory signal comprises or consists of a viral secretory signal.

[0043] In some embodiments, the viral secretory signal comprises or consists of an HSV secretory signal. In some embodiments, the HSV secretory signal comprises or consists of an HSV-1 or HSV-2 secretory signal. In some embodiments, the HSV secretory signal comprises or consists of an HSV glycoprotein D (gD) secretory signal. In some embodiments, the HSV gD secretory signal comprises or consists of an amino acid sequence according to SEQ ID NO: 382. In some embodiments, the HSV gD secretory signal comprises or consists of an amino acid sequence according to SEQ ID NO: 388.

[0044] In some embodiments, the secretory signal comprises or consists of an Ebola virus secretory signal. In some embodiments, the Ebola virus secretory signal comprises or consists of an Ebola virus spike glycoprotein (SGP) secretory signal. In some embodiments, the Ebola virus SGP secretory signal comprises or consists of an amino acid sequence according to SEQ ID NO: 400.

[0045] In some embodiments, the secretory signal is located at the N-terminus of the polypeptide.

[0046] In some embodiments, the polypeptide comprises a transmembrane region.

[0047] In some embodiments, the transmembrane region comprises or consists of a Plasmodium transmembrane region, hi some embodiments, the Plasmodium transmembrane region comprises or consists of a Plasmodium CSP glycosylphosphatidylinositol (GPI) anchor region.

[0048] In some embodiments, the Plasmodium CSP GPI anchor region comprises or consists of the amino acid sequence according to SEQ ID NO:444.

[0049] In some embodiments, the transmembrane region comprises or consists of a heterologous transmembrane region. In some embodiments, the heterologous transmembrane region does not comprise a hemagglutinin transmembrane region. In some embodiments, the heterologous transmembrane region comprises or consists of a non-human transmembrane region. In some embodiments, the heterologous transmembrane region comprises or consists of a viral transmembrane region.

[0050] In some embodiments, the heterologous transmembrane region comprises or consists of an HSV transmembrane region. In some embodiments, the HSV transmembrane region comprises or consists of an HSV-1 or HSV-2 transmembrane region. In some embodiments, the HSV transmembrane region comprises or consists of an HSV gD transmembrane region. In some embodiments, the HSV gD transmembrane region comprises or consists of an amino acid sequence according to SEQ ID NO:447.

[0051] In some embodiments, the transmembrane region comprises or consists of a human transmembrane region. In some embodiments, the human transmembrane region comprises or consists of a human decay-accelerating factor glycosylphosphatidylinositol (hDAF-GPI) anchor region. In some embodiments, the hDAF-GPI anchor region comprises or consists of the amino acid sequence of SEQ ID NO: 450.

[0052] In some embodiments, the polypeptide does not include a secretion signal.

[0053] In some embodiments, the polypeptide does not include a transmembrane region.

[0054] In some embodiments, the polypeptide comprises one or more linkers. In some embodiments, the one or more linkers comprise or consist of an amino acid sequence according to SEQ ID NO: 452. In some embodiments, the one or more linkers comprise or consist of an amino acid sequence according to SEQ ID NO: 459. In some embodiments, the one or more linkers comprise or consist of an amino acid sequence according to SEQ ID NO: 456. In some embodiments, the one or more linkers comprise or consist of an amino acid sequence according to SEQ ID NO: 460.

[0055] In some embodiments, the polypeptide comprises a linker between two Plasmodium T cell antigens.

[0056] In some embodiments, the one or more Plasmodium T cell antigens are one or more P. falciparum T cell antigens. In some embodiments, the one or more P. falciparum T cell antigens are from P. falciparum isolate 3D7. In some embodiments, the one or more Plasmodium T cell antigens are from a Plasmodium species that can infect humans.

[0057] In some embodiments, each of the one or more Plasmodium T cell antigens comprises at least 21 amino acids.

[0058] In some embodiments, the polyribonucleotide is an isolated polyribonucleotide.

[0059] In some embodiments, the polyribonucleotide is an engineered polyribonucleotide.

[0060] In some embodiments, the polyribonucleotide is a codon-optimized polyribonucleotide.

[0061] In some embodiments, in 5' to 3' order: (i) a 5'UTR comprising or consisting of a modified human alpha-globin 5'-UTR; (ii) a polyribonucleotide according to any one of claims 1 to 82; (iii) a 3'UTR comprising or consisting of a first sequence from a split amino-terminal enhancer (AES) messenger RNA and a second sequence from a mitochondrially encoded 12S ribosomal RNA; and (iv) a polyA tail sequence.

[0062] In some embodiments, the 5'UTR comprises or consists of a ribonucleic acid sequence according to SEQ ID NO:465.

[0063] In some embodiments, the 3'UTR comprises or consists of a ribonucleic acid sequence according to SEQ ID NO:471.

[0064] In some embodiments, the polyA tail sequence is a split polyA tail sequence.

[0065] In some embodiments, the split polyA tail sequence comprises or consists of a ribonucleic acid sequence according to SEQ ID NO:467.

[0066] In some embodiments, the RNA construct comprises a 5' cap.

[0067] In some embodiments, the RNA construct comprises a cap-proximal sequence comprising positions +1, +2, +3, +4, and +5 of the polyribonucleotide.

[0068] In some embodiments, the RNA construct comprises a 5' cap comprising or consisting of m7(3'OMeG)(5')ppp(5')(2'OMeA1)pG2, where A1 is at position +1 of the polyribonucleotide and G2 is at position +2 of the polyribonucleotide. In some embodiments, the RNA construct further comprises a cap-proximal sequence comprising A1 and G2 of the Cap1 structure and a sequence comprising A3A4U5 (SEQ ID NO:480) at positions +3, +4, and +5 of the polyribonucleotide, respectively.

[0069] Disclosed herein, in some embodiments, are compositions comprising one or more polyribonucleotides (eg, one or more polyribonucleotides disclosed herein).

[0070] Disclosed herein, in some embodiments, are compositions comprising one or more RNA constructs (eg, one or more RNA constructs disclosed herein).

[0071] In some embodiments, the compositions disclosed herein comprise a lipid nanoparticle, a polyplex (PLX), a lipidated polyplex (LPLX), or a liposome. In some embodiments, one or more polyribonucleotides are fully or partially encapsulated within the lipid nanoparticle, a polyplex (PLX), a lipidated polyplex (LPLX), or a liposome.

[0072] In some embodiments, the compositions disclosed herein further comprise lipid nanoparticles, wherein one or more polyribonucleotides are encapsulated within the lipid nanoparticles. In some embodiments, the lipid nanoparticles target hepatocytes. In some embodiments, the lipid nanoparticles target secondary lymphoid organ cells. In some embodiments, the lipid nanoparticles are cationic lipid nanoparticles.

[0073] In some embodiments, the lipid nanoparticles each comprise: (a) a polymer-conjugated lipid; (b) a cationically ionizable lipid, and (c) one or more neutral lipids.

[0074] In some embodiments, the polymer-conjugated lipid comprises a PEG-conjugated lipid, hi some embodiments, the polymer-conjugated lipid comprises 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide.

[0075] In some embodiments, the one or more neutral lipids comprise 1,2-distearoyl-sn-glycero-3-phosphocholine (DPSC).

[0076] In some embodiments, the one or more neutral lipids comprise cholesterol.

[0077] In some embodiments, the cationically ionizable lipid comprises [(4-hydroxybutyl)azanediyl]di(hexane-6,1-diyl)bis(2-hexyldecanoate).

[0078] In some embodiments, the lipid nanoparticles have an average diameter of about 50-150 nm.

[0079] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a composition (e.g., a composition disclosed herein) and at least one pharmaceutically acceptable excipient. In some embodiments, the pharmaceutical comprises a cryoprotectant, and optionally, the cryoprotectant is sucrose. In some embodiments, the pharmaceutical comprises an aqueous buffer solution, and optionally, the aqueous buffer solution comprises one or more of Tris base, Tris-HCl, NaCl, KCl, NaHPO, and KHPO.

[0080] In some embodiments, the present disclosure provides: (i) a first pharmaceutical composition comprising a first polyribonucleotide, the first polyribonucleotide encoding a first polypeptide, the first polypeptide comprising one or more Plasmodium T cell antigens; and (ii) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, and the second polypeptide comprises one or more Plasmodium antigenic polypeptide regions or portions thereof.

[0081] In some embodiments, the combination comprises a first pharmaceutical composition comprising a polyribonucleotide disclosed herein.

[0082] In some embodiments, the combinations disclosed herein include a second polyribonucleotide that encodes a polypeptide comprising one or more Plasmodium antigenic polypeptide regions or portions thereof and comprising one or more Plasmodium CSP regions or portions thereof.

[0083] In some embodiments, the combination is: (i) a first pharmaceutical composition comprising a polyribonucleotide encoding a first polypeptide, wherein the first polypeptide comprises one or more Plasmodium T cell antigens, and the one or more Plasmodium T cell antigens comprise the Plasmodium N-terminal region or a portion thereof, but do not comprise the Plasmodium C-terminal region or a portion thereof; and (ii) a second pharmaceutical composition comprising a polyribonucleotide encoding a second polypeptide, wherein the second polypeptide comprises one or more Plasmodium CSP polypeptide regions or portions thereof, and the one or more Plasmodium CSP polypeptide regions or portions thereof comprise the Plasmodium CSP C-terminal region or portion thereof, but do not comprise the Plasmodium CSP N-terminal region or portion thereof.

[0084] In some embodiments, a combination disclosed herein comprises a first pharmaceutical composition and a second pharmaceutical composition, wherein the first and second pharmaceutical compositions are not in the same composition.

[0085] In some embodiments, (i) a first pharmaceutical composition comprising a first polyribonucleotide; (ii) a second pharmaceutical composition comprising a second polyribonucleotide; and

[0086] In some embodiments, the present disclosure provides methods comprising administering to a subject a polyribonucleotide (eg, a polyribonucleotide disclosed herein).

[0087] In some embodiments, the present disclosure provides methods that include administering an RNA construct (eg, an RNA construct disclosed herein) to a subject.

[0088] In some embodiments, the present disclosure provides methods comprising administering a composition (eg, a composition disclosed herein) to a subject.

[0089] In some embodiments, the present disclosure provides methods comprising administering one or more doses of a pharmaceutical composition (eg, a pharmaceutical composition disclosed herein) to a subject.

[0090] In some embodiments, the present disclosure provides a pharmaceutical composition for use in treating a malaria infection, the method comprising administering one or more doses of the pharmaceutical composition to a subject.

[0091] In some embodiments, the present disclosure provides a pharmaceutical composition for use in preventing malaria infection comprising administering to a subject one or more doses of the pharmaceutical composition.

[0092] In some embodiments, the methods disclosed herein or the pharmaceutical compositions for the uses disclosed herein comprise administering two or more doses of the pharmaceutical composition to a subject.

[0093] In some embodiments, the method comprises administering three or more doses of the pharmaceutical composition disclosed herein to a subject. In some embodiments, the pharmaceutical composition for use comprises administering three or more doses of the pharmaceutical composition disclosed herein to a subject. In some embodiments, the second dose of the three or more doses is administered to the subject at least four weeks after the first dose of the three or more doses is administered to the subject. In some embodiments, the third dose of the three or more doses is administered to the subject at least four weeks after the second dose of the three or more doses is administered to the subject.

[0094] In some embodiments, the method comprises administering a fourth dose of a pharmaceutical composition disclosed herein to the subject. In some embodiments, the pharmaceutical composition for use comprises administering a fourth dose of a pharmaceutical composition disclosed herein to the subject. In some embodiments, the fourth dose is administered to the subject at least one year after the third dose of the three or more doses is administered to the subject.

[0095] In some embodiments, the method includes administering a combination (e.g., a combination disclosed herein). In some embodiments, the method includes administering a combination comprising a first pharmaceutical composition and a second pharmaceutical composition. In some embodiments, the first and second pharmaceutical compositions are administered on the same day. In some embodiments, the first and second pharmaceutical compositions are administered on different days. In some embodiments, the first and second pharmaceutical compositions are administered to the subject at different locations on the subject's body.

[0096] In some embodiments, the present disclosure provides a method of treating a malaria infection.

[0097] In some embodiments, the present disclosure provides a method of preventing malaria infection.

[0098] In some embodiments, the subject has or is at risk of developing a malaria infection. In some embodiments, the subject is a human.

[0099] In some embodiments, administration of a pharmaceutical composition disclosed herein, a combination disclosed herein, or a polyribonucleotide disclosed herein induces an anti-malarial immune response in a subject. In some embodiments, the anti-malarial immune response in a subject comprises an adaptive immune response. In some embodiments, the anti-malarial immune response comprises a T cell response. In some embodiments, the T cell response is or comprises a CD4+ T cell response, a CD8+ T cell response, and / or a B cell response. In some embodiments, the anti-malarial immune system response comprises the production of antibodies against one or more Plasmodium antigens.

[0100] In some embodiments, the present disclosure provides for the use of a pharmaceutical composition (eg, a pharmaceutical composition described herein) in the treatment of a malaria infection.

[0101] In some embodiments, the present disclosure provides for the use of a pharmaceutical composition (eg, a pharmaceutical composition described herein) in the prevention of malaria infection.

[0102] In some embodiments, the present disclosure provides for the use of a pharmaceutical composition (eg, a pharmaceutical composition disclosed herein) in inducing an anti-malarial immune response in a subject.

[0103] In some embodiments, the present disclosure provides polypeptides encoded by the polyribonucleotides described herein.

[0104] In some embodiments, the present disclosure provides polypeptides encoded by the RNA constructs described herein.

[0105] In some embodiments, the present disclosure provides a host cell comprising a polyribonucleotide (e.g., a polyribonucleotide described herein).

[0106] In some embodiments, the disclosure includes a host cell (e.g., a host cell comprising a polyribonucleotide disclosed herein, an RNA construct described herein, and / or a polypeptide disclosed herein). [Brief explanation of the drawings]

[0107] [Figure 1]

[0023] Figure 1 shows an exemplary workflow for identifying, selecting, and / or characterizing antigens (e.g., Plasmodium proteins, including specific variants, and / or epitopes thereof, particularly T cell epitopes) for use in accordance with the present disclosure. [Figure 2A] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2B] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2C] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2D]1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2E] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2F] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2G] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2H] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2I]1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2J] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2K] 1 shows the immunological characterization of 11 Plasmodium proteins (specifically, CSP, TRAP, EXP1, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-1, LSA-3, LSAP1, and LSAP2), and fragments selected for inclusion in antigens (e.g., string construct antigens) for use in accordance with the present disclosure. [Figure 2L-1] 1 shows antigenic fragments of Plasmodium polypeptides encoded by exemplary RNA constructs described herein. [Figure 2L-2] Same as above. [Figure 2L-3] Same as above. [Figure 2M] 1 shows an antigenic fragment of the Plasmodium protein LSA-3. [Figure 3] FIG. 1 shows a schematic diagram of an exemplary antigen-containing Plasmodium T-cell string polypeptide construct as described herein. [Figure 4A] Figure 1 shows T cell activation as assessed by IFN-γ secretion. An exemplary study design is shown, including dosing and peptide string construct design. [Figure 4B]Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 4C] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 4D] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 4E] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. Figure 2 shows a comparison of the responses of isolated splenocytes (from mice in groups 2 and 3 with splenocytes isolated from mice in group 4) to specific antigen peptide pools. [Figure 4F] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. Figure 2 shows a comparison of the responses of isolated splenocytes (from mice in group 2 and splenocytes isolated from mice in group 1) to specific antigen peptide pools. [Figure 5A] Figure 1 shows T cell activation as assessed by IFN-γ secretion. An exemplary study design is shown, including dosing and peptide string construct design. [Figure 5B] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5C]Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5D] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5E] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5F] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5G] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5H] Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 5I]Figure 1 shows T cell activation, as assessed by IFN-γ secretion. IFN-γ secretion is assessed using isolated splenocytes (from mice immunized with various T cell peptide string constructs) incubated with construct-specific antigen peptide pools (15mers, 11 aa overlap across the antigen). [Figure 6A] 1 shows an assessment of T cell activation, as assessed by IFN-γ secretion, using isolated splenocytes (from mice immunized with T cell peptide string constructs individually or in combination with T cell string constructs). [Figure 6B] 1 shows an assessment of T cell activation, as assessed by IFN-γ secretion, using isolated splenocytes (from mice immunized with T cell peptide string constructs individually or in combination with T cell string constructs). [Figure 7A] 1 shows the evaluation of T cell activation, as assessed by IFN-γ secretion, using isolated splenocytes (from mice immunized with short T cell peptide string constructs or long T cell peptide strings with the same antigen content). [Figure 7B] 1 shows the evaluation of T cell activation, as assessed by IFN-γ secretion, using isolated splenocytes (from mice immunized with short T cell peptide string constructs or long T cell peptide strings with the same antigen content). [Figure 8] Figure 1 shows the transfection of cells with a combination containing RNA constructs 55 and 57 to generate a detectable protein product. Relative protein expression 24 hours after co-transfection of 2.5 μg of each formulation into the HEK293T cell line is shown.

[0108] definition The compounds of the present disclosure include those outlined above and are further represented by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise specified. For the purposes of this disclosure, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Edition. Furthermore, the general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry", 5th Edition: Smith, MB and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are incorporated herein by reference.

[0109] Unless otherwise specified, structures depicted herein are intended to include all stereoisomeric (e.g., enantiomeric or diastereomeric) forms of the structure, as well as all geometric or conformational isomeric forms of the structure. For example, R and S configurations of each stereocenter are contemplated as part of the present disclosure. Accordingly, single stereochemical isomers of the provided compounds, as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures, are within the scope of the present disclosure. For example, in some cases, the provided compounds represent one or more stereoisomers of the compound, and unless otherwise specified, each stereoisomer is represented alone and / or as a mixture. Unless otherwise specified, all tautomeric forms of the provided compounds are within the scope of the present disclosure.

[0110] Unless otherwise stated, structures depicted herein are meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of a hydrogen by deuterium or tritium, or the replacement of a carbon by a C- or C-enriched carbon are within the scope of this disclosure.

[0111] About: The term "about," as used herein with respect to a value, refers to a value that is similar in relation to the referenced value. Generally, the appropriate degree of variation encompassed by "about" in that context will be understood by one of ordinary skill in the art familiar with the context. For example, in some embodiments, the term "about" can encompass a range of values ​​within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less of the referenced value.

[0112] Drug: As used herein, the term "drug" may refer to a physical entity. In some embodiments, a drug may be characterized by particular characteristics and / or effects. For example, as used herein, the term "therapeutic agent" refers to a physical entity that has a therapeutic effect and / or induces a desired biological and / or pharmacological effect. In some embodiments, a drug may be a compound, molecule, or entity of any chemical class, including, for example, a small molecule, a polypeptide, a nucleic acid, a monosaccharide, a lipid, a metal, or a combination or complex thereof.

[0113] Amino acid: In its broadest sense, as used herein, the term "amino acid" refers to a compound and / or substance that can be, is, or is incorporated into a polypeptide chain, for example, by the formation of one or more peptide bonds. In some embodiments, an amino acid has the general structure HN-C(H)(R)-COOH. In some embodiments, an amino acid is a naturally occurring amino acid. In some embodiments, an amino acid is a non-naturally occurring amino acid; in some embodiments, an amino acid is a D-amino acid; in some embodiments, an amino acid is an L-amino acid. A "standard amino acid" refers to any of the 20 standard L-amino acids commonly found in naturally occurring peptides. A "non-standard amino acid" refers to any amino acid other than the standard amino acids, whether prepared synthetically or obtained from a natural source. In some embodiments, amino acids, including the carboxy- and / or amino-terminal amino acids in a polypeptide, may contain structural modifications compared to the general structures above. For example, in some embodiments, an amino acid may be modified relative to the general structure by methylation, amidation, acetylation, pegylation, glycosylation, phosphorylation, and / or substitution (e.g., of an amino group, a carboxylic acid group, one or more protons, and / or a hydroxyl group). In some embodiments, such modifications may alter the circulating half-life of a polypeptide containing the modified amino acid compared to one containing an otherwise identical, unmodified amino acid. In some embodiments, such modifications do not significantly alter the relevant activity of a polypeptide comprising the modified amino acid compared to one otherwise identical that comprises the unmodified amino acid. As will be clear from the context, in some embodiments, the term "amino acid" may be used to refer to a free amino acid; in some embodiments, the term may be used to refer to an amino acid residue of a polypeptide.

[0114] Antigen: As used herein, the term "antigen" refers to an agent that elicits an immune response and / or that binds to a T cell receptor (e.g., when presented by an MHC molecule) or an antibody.

[0115] Anti-malarial immune response: As used herein, the term "anti-malarial immune response" refers to an immune response against one or more antigens derived from Plasmodium.

[0116] Associated: Two events or entities are "associated" with one another, as this term is used herein, when the presence, level, degree, type, and / or form of one correlates with that of the other. For example, a particular entity (e.g., a polypeptide, genetic signature, metabolite, microorganism, etc.) is considered associated with a particular disease, disorder, or condition if its presence, level, and / or form correlates with the occurrence, susceptibility, severity, stage, etc. of the disease, disorder, or condition (e.g., across a relevant population). In some embodiments, two or more entities are physically "associated" with one another if they directly or indirectly interact to bring them into and / or maintain them in close physical proximity to one another. In some embodiments, two or more entities that are physically associated with one another are covalently linked to one another. In some embodiments, two or more entities that are physically associated with one another are not covalently linked to one another, but are non-covalently associated, for example, by hydrogen bonding, van der Waals interactions, hydrophobic interactions, magnetism, and combinations thereof.

[0117] C-terminal domain: As used herein, the term "C-terminal domain" refers to the region of the CSP polypeptide corresponding to amino acids 273 to 397 of the wild-type CSP sequence of Plasmodium falciparum (isolate 3D7) (SEQ ID NO: 1).

[0118] C-terminal region: As used herein, the term "C-terminal region" refers to the region of a CSP polypeptide corresponding to amino acids 273-375 of the wild-type CSP sequence (SEQ ID NO: 1). In some embodiments, a serine immediately follows the C-terminal region. In some embodiments, a serine and a valine immediately follow the C-terminal region.

[0119] Central domain: The term "central domain," as used herein, refers to the region of a CSP polypeptide corresponding to amino acids 105 to 272 of the wild-type CSP sequence (SEQ ID NO: 1).

[0120] Combination therapy: As used herein, the term "combination therapy" refers to a situation in which a subject is exposed to two or more therapeutic regimens (e.g., two or more therapeutic agents (e.g., two or more antibody agents)) simultaneously. In some embodiments, the two or more regimens may be administered simultaneously. In some embodiments, the regimens may be administered sequentially (e.g., all "doses" of a first regimen are administered before any doses of a second regimen are administered). In some embodiments, the agents are administered in overlapping dosing regimens. In some embodiments, administration of combination therapy may involve administering one or more agent(s) or modality(s) to a subject receiving other agent(s) or modality(s) being combined. For clarity, combination therapy does not require that the individual agents be administered together in a single composition (or even necessarily simultaneously), although in some embodiments, two or more agents or active portions thereof may be administered together in a combined composition.

[0121] Comparable: As used herein, the term "equivalent" refers to two or more agents, entities, circumstances, sets of conditions, etc. that may not be identical to one another, but are sufficiently similar to permit a comparison between them where one of skill in the art would understand that conclusions can be reasonably drawn based on observed differences or similarities. In some embodiments, comparable sets of conditions, circumstances, individuals, or populations are characterized by multiple substantially identical characteristics and one or a few different characteristics. One of skill in the art will understand the degree of identity required for two or more such agents, entities, circumstances, sets of conditions, etc. to be considered comparable in any given situation in context. For example, one of skill in the art will understand that sets of circumstances, individuals, or populations are comparable to one another if they are characterized by a sufficient number and type of substantially identical characteristics to warrant a reasonable conclusion that differences in results obtained or phenomena observed under or with different sets of circumstances, individuals, or populations are caused by, or indicate, variations in those characteristics.

[0122] Corresponding to: As used herein, the term "corresponding to" refers to a relationship between two or more entities. For example, the term "corresponding to" can be used to designate the position / identity of a structural element in one compound or composition relative to another compound or composition (e.g., relative to an appropriate reference compound or composition). For example, in some embodiments, a monomer residue in a polymer (e.g., an amino acid residue in a polypeptide or a nucleic acid residue in a polynucleotide) can be identified as "corresponding to" a residue in an appropriate reference polymer. For example, one of skill in the art will understand that, for simplicity's sake, residues in a polypeptide are often designated based on the relevant reference polypeptide using a standard numbering system, so that an amino acid "corresponding to" a residue at position 190 corresponds to the residue found at position 190 in the reference polypeptide, for example, without necessarily being the actual 190th amino acid in a particular amino acid chain; one of skill in the art will readily understand how to identify a "corresponding" amino acid. For example, those skilled in the art will recognize various alignment strategies, e.g., software programs such as BLAST, CS-BLAST, CUSASW++, DIAMOND, FASTA, GGSEARCH / GLSEARCH, Genoogle, HMMER, HHpred / HHsearch, IDF, Infernal, KLAST, USEARCH, parasail, PSI-BLAST, PSI-Search, ScalaBLAST, Sequilab, SAM, SSEARCH, SWAPHI, SWAPHI-LS, SWIMM, or SWIPE, that can be utilized to identify "corresponding" residues in, for example, polypeptides and / or nucleic acids in accordance with the present disclosure. Those skilled in the art will also recognize that the term "corresponding to" can sometimes be used to refer to an event or entity that has meaningful similarity to another event or entity (e.g., an appropriate reference event or entity). As an example, a gene or protein in one organism can be described as "corresponding to" a gene or protein from another organism.The purpose, in some embodiments, is to show that it plays a similar role or performs a similar function, and / or that it exhibits a particular degree of sequence identity or homology or shares particular characteristic sequence elements.

[0123] Dosing regimen: Those skilled in the art will understand that the term "dosing regimen" (or "therapeutic regimen") can be used to refer to a set of unit doses (typically two or more) administered individually, typically over time, to a subject. In some embodiments, a given therapeutic agent has a recommended dosing regimen that can include one or more doses.

[0124] Encode: As used herein, the terms "encode" or "encoding" refer to the sequence information of a first molecule that directs the production of a second molecule having a defined sequence of nucleotides (e.g., polyribonucleotides) or a defined sequence of amino acids. For example, a DNA molecule can encode an RNA molecule (e.g., by a transcription process involving a DNA-dependent RNA polymerase enzyme). An RNA molecule can encode a polypeptide (e.g., by a translation process). Thus, a gene, cDNA, or RNA molecule encodes a polypeptide if the polypeptide is produced in a cell or other biological system by transcription and translation of the RNA corresponding to that gene. In some embodiments, the coding region of a polyribonucleotide encoding a target antigen refers to the coding strand, the nucleotide sequence of which is identical to the polyribonucleotide sequence of such target antigen. In some embodiments, the coding region of a polyribonucleotide encoding a target antigen refers to the non-coding strand of such target antigen, the non-coding strand being one that can be used as a template for transcription of the gene or cDNA.

[0125] Expression: As used herein, the term "expression" of a nucleic acid sequence refers to the production of a gene product from the nucleic acid sequence. In some embodiments, the gene product can be a transcription product, e.g., a polyribonucleotide as provided herein. In some embodiments, the gene product can be a polypeptide. In some embodiments, expression of a nucleic acid sequence involves one or more of: (1) generation of an RNA template from the DNA sequence (e.g., by transcription); (2) processing of the RNA transcript (e.g., by splicing, editing, etc.); (3) translation of the RNA into a polypeptide or protein; and / or (4) post-translational modification of the polypeptide or protein.

[0126] Heterologous: As used herein, the term "heterologous" in reference to a secretory signal or transmembrane region refers to a secretory signal or transmembrane region from a virus or organism other than Plasmodium.

[0127] Homology: As used herein, the term "homologous" or "homology" refers to the overall relatedness between polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or polypeptide molecules. In some embodiments, polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or polypeptide molecules are considered to be "homologous" to one another if their sequences are at least 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical. In some embodiments, polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or polypeptide molecules are considered to be "homologous" to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% similar (e.g., containing residues with related chemical properties at corresponding positions). For example, as is well known to those of skill in the art, certain amino acids are typically classified as "hydrophobic" or "hydrophilic" amino acids and / or as having "polar" or "nonpolar" side chains, similar to one another. Substitution of one amino acid for another amino acid of the same type can often be considered a "homologous" substitution.

[0128] Identity: As used herein, the term "identity" refers to the overall relatedness between polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or polypeptide molecules. In some embodiments, polynucleotide molecules (e.g., DNA molecules and / or RNA molecules) and / or polypeptide molecules are considered to be "substantially identical" to one another if their sequences are at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical. For example, calculation of the percent identity of two nucleic acid or polypeptide sequences can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced into one or both of the first and second sequences for optimal alignment, and non-identical sequences can be disregarded for comparison purposes). In certain embodiments, the length of sequences aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or substantially 100% of the length of the reference sequence. Nucleotides at corresponding positions are then compared. If a position in the first sequence is occupied by the same residue as the corresponding position in the second sequence, the molecules are identical at that position. The percent identity between two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps and the length of each gap that need to be introduced for optimal alignment of the two sequences. Sequence comparison and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. For example, the percent identity of two nucleotide sequences can be determined using the algorithm of Meyers and Miller (1989) incorporated into the ALIGN program (version 2.0). In some exemplary embodiments, nucleic acid sequence comparisons generated with the ALIGN program use a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4.The percent identity between two nucleotide sequences can alternatively be determined using the GAP program in the GCG software package using the NWSgapdna.CMP matrix.

[0129] Increase, induce, or reduce: As used herein, these terms, or grammatically equivalent comparative terms, refer to values ​​that are relative to an equivalent reference measurement. For example, in some embodiments, an assessment value obtained using a provided composition (e.g., a pharmaceutical composition) may be "increased" compared to an assessment value obtained using a comparable reference composition. Alternatively or additionally, in some embodiments, an assessment value obtained in a subject may be "increased" compared to an assessment value obtained in the same subject under different conditions (e.g., before or after an event, or in the presence or absence of an event, e.g., administration of a composition (e.g., a pharmaceutical composition) described herein) or in a different comparable subject (e.g., in a comparable subject that differs from the subject of interest in being exposed to a prior condition, e.g., the absence of administration of a composition (e.g., a pharmaceutical composition) described herein). In some embodiments, comparative terms refer to a statistically significant difference (e.g., of sufficient predominance and / or magnitude to achieve statistical significance). Determining the degree and / or extent of the difference necessary or sufficient to achieve such statistical significance in a given situation is recognized or readily possible by those skilled in the art. In some embodiments, the term "reduce" or equivalent terms refers to a reduction in the level of an assessed value by at least 5%, at least 10%, at least 20%, at least 50%, at least 75%, or more relative to a comparable reference. In some embodiments, the term "reduce" or equivalent terms refers to complete or substantially complete inhibition, i.e., a reduction to zero or substantially zero. In some embodiments, the term "increased" or "induced" refers to an increase in the level of an assessed value by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 80%, at least 100%, at least 200%, at least 500%, or more relative to an equivalent reference.

[0130] In order: As used herein with respect to a polynucleotide or polyribonucleotide, "in order" refers to the order of features from 5' to 3' along the polynucleotide or polyribonucleotide. As used herein with respect to a polypeptide, "in order" refers to the order of features along the polypeptide, moving from the most N-terminal feature to the most C-terminal feature. "In order" does not mean that there cannot be additional features between the listed features. For example, if features A, B, and C of a polynucleotide are described herein as being "in order, feature A, feature B, and feature C," this description does not exclude, for example, feature D from being located between feature A and feature B.

[0131] Isolated: The term "isolated" means altered or removed from the natural state. For example, a nucleic acid or peptide that is naturally present in a living animal is not "isolated," but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is "isolated." An isolated nucleic acid or protein can exist in a substantially purified form, or can exist in a non-native environment, such as, for example, a host cell.

[0132] Junction region: As used herein, the term "junction region" refers to the region of a CSP polypeptide corresponding to amino acids 93-104 of the wild-type CSP sequence (SEQ ID NO: 1).

[0133] Junction region variant: As used herein, the term "junction region variant" refers to a junction region that contains one or more substitution mutations compared to amino acids 93-104 of the wild-type CSP sequence (SEQ ID NO: 1).

[0134] Linker: As used herein, the term "linker" refers to a portion of a polypeptide that connects different regions, moieties, or antigens to one another.

[0135] Lipid: As used herein, the terms "lipid" and "lipid-like material" are broadly defined as molecules that contain one or more hydrophobic moieties or groups, and optionally also one or more hydrophilic moieties or groups. Molecules that contain hydrophobic and hydrophilic moieties are also typically referred to as amphiphiles.

[0136] Major repeat region: As used herein, the term "major repeat region" refers to a region of a CSP polypeptide corresponding to amino acids 129-272 of the wild-type CSP sequence (SEQ ID NO: 1) and containing 35 repeats of the amino acid sequence NANP (SEQ ID NO: 108). The 35 repeats of the amino acid sequence NANP (SEQ ID NO: 108) are separated into two contiguous stretches, the first containing 17 repeats of the amino acid sequence NANP (SEQ ID NO: 108) and the second containing 18 repeats of the amino acid sequence NANP (SEQ ID NO: 108) adjacent to the amino acid sequence of NVDP (SEQ ID NO: 105). A portion of the major repeat region contains at least the amino acid sequence NPNA (SEQ ID NO: 104). Preferably, a portion of the major repeat region contains at least the amino acid sequences NANPNA (SEQ ID NO: 114) and NPNANP (SEQ ID NO: 111). As used herein, "repeat" with respect to sequence A refers to the presence of sequence A once, and "one or more repeats" of sequence A refers to the presence of sequence A more than once.

[0137] Merozoite stage-specific Plasmodium antigen: As used herein, the term "merozoite stage-specific Plasmodium antigen" refers to an antigen that is expressed during the merozoite stage of the Plasmodium life cycle.

[0138] Minority repeat region: As used herein, the term "minority repeat region" refers to a region of a CSP polypeptide corresponding to amino acids 105-128 of the wild-type CSP sequence (SEQ ID NO: 1) and containing three repeats of the amino acid sequence NANPNVDP (SEQ ID NO: 477). The minority repeat region does not contain the amino acid sequence NPNA (SEQ ID NO: 104) and does not contain the amino acid sequences NANPNA (SEQ ID NO: 114) or NPNANP (SEQ ID NO: 111). As used herein, "repeat" with respect to sequence A refers to the presence of sequence A once, and "three repeats" of sequence A refers to the presence of sequence A three or more times.

[0139] N-terminal domain: As used herein, the term "N-terminal domain" refers to the region of a CSP polypeptide corresponding to amino acids 19-92 of the wild-type CSP sequence (SEQ ID NO: 1).

[0140] N-terminal end region: As used herein, the term "N-terminal end region" refers to the region of a CSP polypeptide corresponding to amino acids 81-92 of the wild-type CSP sequence (SEQ ID NO: 1).

[0141] N-terminal region: As used herein, the term "N-terminal region" refers to the region of a CSP polypeptide corresponding to amino acids 19-80 of the wild-type CSP sequence (SEQ ID NO: 1).

[0142] RNA lipid nanoparticles: As used herein, the term "RNA lipid nanoparticles" refers to nanoparticles comprising at least one lipid and RNA molecule(s), such as one or more polyribonucleotides provided herein. In some embodiments, the RNA lipid nanoparticles comprise at least one cationic amino lipid. In some embodiments, the RNA lipid nanoparticles comprise at least one cationic amino lipid, at least one helper lipid, and at least one polymer-conjugated lipid (e.g., PEG-conjugated lipid). In various embodiments, the RNA lipid nanoparticles described herein can have an average size (e.g., Z-average) of about 100 nm to 1000 nm, or about 200 nm to 900 nm, or about 200 nm to 800 nm, or about 250 nm to about 700 nm. In some embodiments of the present disclosure, the RNA-lipid nanoparticles may have a particle size (e.g., Z-average) of about 30 nm to about 200 nm, or about 30 nm to about 150 nm, about 40 nm to about 150 nm, about 50 nm to about 150 nm, about 60 nm to about 130 nm, about 70 nm to about 110 nm, about 70 nm to about 100 nm, about 80 nm to about 100 nm, about 90 nm to about 100 nm, about 70 nm to about 90 nm, about 80 nm to about 90 nm, or about 70 nm to about 80 nm. In some embodiments, the average particle size of the lipid nanoparticles is determined by measuring the average particle diameter. In some embodiments, the RNA-lipid nanoparticles may be prepared by mixing lipids with the RNA molecules described herein.

[0143] Neutralization: As used herein, the term "neutralization" refers to an event in which a binding agent, such as an antibody, binds to a biologically active site on a parasite, such as a receptor-binding protein, thereby inhibiting parasite infection of a cell. In some embodiments, the term "neutralization" refers to an event in which the ability of the binding agent to infect a cell is eliminated or significantly reduced.

[0144] Nucleic Acid / Polynucleotide: As used herein, the term "nucleic acid" refers to a polymer of at least 10 nucleotides or more. In some embodiments, a nucleic acid is or comprises DNA. In some embodiments, a nucleic acid is or comprises RNA. In some embodiments, a nucleic acid is or comprises peptide nucleic acid (PNA). In some embodiments, a nucleic acid is or comprises single-stranded nucleic acid. In some embodiments, a nucleic acid is or comprises double-stranded nucleic acid. In some embodiments, a nucleic acid comprises both single-stranded and double-stranded portions. In some embodiments, a nucleic acid comprises a backbone comprising one or more phosphodiester bonds. In some embodiments, a nucleic acid comprises a backbone having both phosphodiester and non-phosphodiester bonds. For example, in some embodiments, a nucleic acid can comprise a backbone comprising one or more phosphorothioate or 5'-N-phosphoramidite bonds and / or one or more peptide bonds, e.g., "peptide nucleic acids." In some embodiments, a nucleic acid comprises one or more, or all, naturally occurring residues (e.g., adenine, cytosine, deoxyadenosine, deoxycytidine, deoxyguanosine, deoxythymidine, guanine, thymine, uracil). In some embodiments, a nucleic acid comprises one or more, or all, non-naturally occurring residues. In some embodiments, the non-natural residue comprises a nucleoside analog (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyladenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, 6-O-methylguanine, 2-thiocytidine, methylated bases, intercalating bases, and combinations thereof).In some embodiments, the non-natural residue comprises one or more modified sugars (e.g., 2'-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose) compared to that of the natural residue. In some embodiments, the nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or a polypeptide. In some embodiments, the nucleic acid has a nucleotide sequence that includes one or more introns. In some embodiments, the nucleic acid can be prepared by isolation from a natural source, enzymatic synthesis (e.g., by polymerization based on a complementary template in vivo or in vitro), replication in a recombinant cell or system, or chemical synthesis. In some embodiments, the nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 20, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 9000, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2250, 2500, 275, 3000, 3250, 3500, 375, 4000, 4250, 4500, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, and 500, 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10,000, 10,500, 11,000, 11,500, 12,000, 12,500, 13,000, 13,500, 14,000, 14,500, 15,000, 15,500, 16,000, 16,500, 17,000, 17,500, 18,000, 18,500, 19,000, 19,500, or 20,000 or more residues or nucleotides in length.

[0145] Pharmaceutically effective amount: The term "pharmaceutically effective amount" or "therapeutically effective amount" refers to an amount that achieves a desired response or a desired effect, either alone or together with further doses. In the case of treating a particular disease (e.g., malaria), the desired response in some embodiments relates to inhibiting the progression of the disease (e.g., malaria). In some embodiments, such inhibition can include slowing the progression of the disease (e.g., malaria) and / or halting or reversing the progression of the disease (e.g., malaria). In some embodiments, the desired response in treating a disease (e.g., malaria) can be or can include delaying or preventing the onset of the disease (e.g., malaria) or condition (e.g., a malaria-related condition). Effective amounts of the compositions (e.g., pharmaceutical compositions) described herein will depend on individual patient parameters, including, for example, the disease (e.g., malaria) or condition (e.g., a malaria-related condition) to be treated, the severity of such disease (e.g., malaria) or condition (e.g., a malaria-related condition), e.g., age, physiological state, size and weight, duration of treatment, type of concomitant therapy (if any), the particular route of administration, and similar factors. Thus, the dose of the compositions (e.g., pharmaceutical compositions) described herein may depend on various such parameters. If the patient does not respond to the initial dose, a higher dose (or an effectively higher dose achieved by a different, more localized route of administration) may be used.

[0146] Polypeptide: As used herein, the term "polypeptide" refers to a polymeric chain of amino acids. In some embodiments, a polypeptide has a naturally occurring amino acid sequence. In some embodiments, a polypeptide has a non-naturally occurring amino acid sequence. In some embodiments, a polypeptide has an engineered amino acid sequence, in that it has been designed and / or produced by human activity. In some embodiments, a polypeptide can include or consist of natural amino acids, unnatural amino acids, or both. In some embodiments, a polypeptide can include only natural amino acids, only unnatural amino acids, or only natural amino acids, or only unnatural amino acids. In some embodiments, a polypeptide can include D-amino acids, L-amino acids, or both. In some embodiments, a polypeptide can include only D-amino acids. In some embodiments, a polypeptide can include only L-amino acids. In some embodiments, a polypeptide can include one or more pendant groups or other modifications, e.g., one or more amino acid side chains modified or attached to one or more amino acid side chains at the N-terminus of the polypeptide, the C-terminus of the polypeptide, or any combination thereof. In some embodiments, such pendant groups or modifications include acetylation, amidation, lipidation, methylation, pegylation, etc. (including combinations thereof). In some embodiments, a polypeptide may be cyclic and / or include a cyclic moiety. In some embodiments, a polypeptide is not cyclic and / or does not include a cyclic moiety. In some embodiments, a polypeptide is linear. In some embodiments, a polypeptide may be or include a stapled polypeptide. In some embodiments, the term "polypeptide" may be appended to the name of a reference polypeptide, activity, or structure, and in such cases, it is used herein to refer to polypeptides that share a related activity or structure and therefore can be considered members of the same class or family of polypeptides.For each such class, the present specification provides, and / or one of skill in the art will recognize, exemplary polypeptides within the class whose amino acid sequence and / or function are known. In some embodiments, such exemplary polypeptides are reference polypeptides of a class or family of polypeptides. In some embodiments, members of a polypeptide class or family exhibit significant sequence homology or identity with the reference polypeptide of the class (and, in some embodiments, with all polypeptides in the class), share common sequence motifs (e.g., characteristic sequence elements), and / or share a common activity (in some embodiments, at a similar level or within a specified range) with the reference polypeptide of the class (and, in some embodiments, with all polypeptides in the class). For example, in some embodiments, a member polypeptide exhibits a degree of overall sequence homology or identity with a reference polypeptide of at least about 30-40%, often greater than about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, and / or comprises at least one region (e.g., a conserved region, which in some embodiments may be or may include a distinctive sequence element) that exhibits very high sequence identity, often greater than 90%, or even greater than 95%, 96%, 97%, 98%, or 99%. Such conserved regions typically encompass at least 3-4, and often up to 35 or more, amino acids; in some embodiments, the conserved region encompasses at least a stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or more consecutive amino acids. In some embodiments, the related polypeptide may comprise or consist of a fragment of a parent polypeptide. In some embodiments, the polypeptide is a Plasmodium T-cell string polypeptide construct described herein.A Plasmodium T cell string polypeptide construct is a polypeptide that comprises one or more T cell antigens from one or more Plasmodium proteins or one or more portions thereof. In some embodiments, the Plasmodium T cell string polypeptide construct further comprises one or more additional amino acid sequences, such as a secretory signal (e.g., a heterologous secretory signal), a transmembrane region (e.g., a heterologous transmembrane region), a trafficking signal, and / or a linker, as described herein.

[0147] Prevention: As used herein, the terms "prevent" or "prevention," when used in reference to the occurrence of a disease, disorder, and / or condition, refers to a reduction in the risk of developing a disease, disorder, and / or condition and / or a delay in the onset of one or more characteristics or symptoms of the disease, disorder, or condition. Prevention may be considered complete if the onset of the disease, disorder, or condition is delayed for a predefined period of time. In some embodiments, prevention refers to a reduction in the risk of developing clinical malaria.

[0148] Reference: As used herein, the term "reference" describes a standard or control against which a comparison is made. For example, in some embodiments, an agent, animal, individual, population, sample, sequence, or value of interest is compared to a reference or control agent, animal, individual, population, sample, sequence, or value. In some embodiments, the reference or control is tested and / or measured substantially simultaneously with the test or measurement of interest. In some embodiments, the reference or control is a historical reference or control, optionally embodied in a tangible medium. Typically, as will be apparent to one of skill in the art, a reference or control is measured or characterized under conditions or circumstances comparable to those being evaluated. One of skill in the art will understand when there is sufficient similarity to justify reliance on and / or comparison to a particular reference or control considered.

[0149] Ribonucleic acid (RNA) or polyribonucleotide: As used herein, the terms "ribonucleic acid," "RNA," or "polyribonucleotide" refer to a polymer of ribonucleotides. In some embodiments, the RNA is single-stranded. In some embodiments, the RNA is double-stranded. In some embodiments, the RNA contains both single-stranded and double-stranded portions. In some embodiments, the RNA may contain a backbone structure described in the definition of "nucleic acid / polynucleotide" above. The RNA may be a regulatory RNA (e.g., siRNA, microRNA, etc.) or a messenger RNA (mRNA). In some embodiments, the RNA is an mRNA. In some embodiments where the RNA is an mRNA, the RNA typically contains a poly(A) region at its 3' end. In some embodiments, the RNA is an mRNA, and the RNA typically contains an art-recognized cap structure at its 5' end for, for example, recognition and attachment of the mRNA to a ribosome to initiate translation. In some embodiments, the RNA is synthetic RNA. Synthetic RNA includes RNA synthesized in vitro (e.g., by enzymatic and / or chemical synthesis). In some embodiments, the polyribonucleotide encodes a polypeptide, which is preferably a Plasmodium T-cell string polypeptide construct.

[0150] Ribonucleotide: As used herein, the term "ribonucleotide" encompasses unmodified ribonucleotides and modified ribonucleotides. For example, unmodified ribonucleotides include the purine bases adenine (A) and guanine (G) and the pyrimidine bases cytosine (C) and uracil (U). Modified ribonucleotides can include one or more modifications, including, but not limited to, (a) terminal modifications, such as 5'-terminal modifications (e.g., phosphorylation, dephosphorylation, conjugation, inverted linkage, etc.), 3'-terminal modifications (e.g., conjugation, inverted linkage, etc.), (b) base modifications, such as replacement with a modified base, a stabilized base, a destabilized base, or a base that base pairs with an expanded repertoire of partners, or a conjugated base, (c) sugar modifications (e.g., at the 2' or 4' position) or sugar replacement, and (d) internucleoside linkage modifications, including modification or replacement of a phosphodiester bond. The term "ribonucleotide" also encompasses ribonucleotide triphosphates, including modified and unmodified ribonucleotide triphosphates.

[0151] Secretory signal: As used herein, the term "secretory signal" refers to an amino acid sequence motif that targets an associated polypeptide for entry into the secretory pathway.

[0152] Subject: As used herein, the term "subject" refers to an organism administered with a composition described herein, e.g., for experimental, diagnostic, prophylactic, and / or therapeutic purposes. Typical subjects include animals (e.g., mice, rats, rabbits, non-human primates, household pets, etc.) and humans. In some embodiments, the subject is a human subject. In some embodiments, the subject is afflicted with a disease, disorder, or condition (e.g., malaria and / or a malaria-related condition). In some embodiments, the subject is susceptible to a disease, disorder, or condition (e.g., malaria and / or a malaria-related condition). In some embodiments, the subject exhibits one or more symptoms or characteristics of a disease, disorder, or condition (e.g., malaria and / or a malaria-related condition). In some embodiments, the subject exhibits one or more non-specific symptoms of a disease, disorder, or condition (e.g., malaria and / or a malaria-related condition). In some embodiments, the subject does not exhibit any symptoms or characteristics of a disease, disorder, or condition (e.g., malaria and / or a malaria-related condition). In some embodiments, a subject is one who has one or more features characteristic of susceptibility to or risk of a disease, disorder, or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, a subject is a patient. In some embodiments, a subject is an individual who is being and / or has been administered a diagnosis and / or therapy.

[0153] Suffering from: An individual who is "suffering from" a disease, disorder, and / or condition (e.g., malaria and / or a malaria-related condition) has and / or displays one or more symptoms of the disease, disorder, and / or condition.

[0154] Susceptible to: An individual who is "susceptible to" a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) is an individual who has a higher risk of developing the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) than members of the general public. In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) may not have been diagnosed with the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) may exhibit symptoms of the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) may not exhibit symptoms of the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) develops the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, an individual who is susceptible to a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions) does not exhibit symptoms of the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions).

[0155] Therapy: The term "therapy" refers to the administration or delivery of an agent or intervention that has a therapeutic effect and / or induces a desired biological and / or pharmacological effect (e.g., that has been demonstrated to be statistically likely to have such an effect when administered to a relevant population). In some embodiments, a therapeutic agent or therapy is any substance that can be used to alleviate, ameliorate, reduce, inhibit, prevent, delay onset, reduce severity, and / or reduce incidence of one or more symptoms or characteristics of a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, a therapeutic agent or therapy is a medical intervention that can be performed to alleviate, alleviate, inhibit, present, delay onset, reduce severity, and / or reduce incidence of one or more symptoms or characteristics of a disease, disorder, and / or condition.

[0156] Transmembrane domain: As used herein, the term "transmembrane domain" refers to the region of a polypeptide that spans a biological membrane, such as the plasma membrane of a cell.

[0157] Treat: As used herein, the terms "treat," "treatment," or "treating" refer to any method used to partially or completely alleviate, ameliorate, relieve, inhibit, prevent, delay the onset of, reduce the severity of, and / or reduce the incidence of one or more symptoms or characteristics of a disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). Treatment may be administered to a subject who does not exhibit symptoms of the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions). In some embodiments, treatment may be administered to a subject who exhibits only early signs of the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions), e.g., to reduce the risk of developing conditions associated with the disease, disorder, and / or condition. In some embodiments, treatment may be administered to a subject at a later stage of the disease, disorder, and / or condition (e.g., malaria and / or malaria-related conditions).

[0158] Variant: As used herein, the term "variant" refers to a molecule that exhibits significant structural identity (e.g., primary or secondary) with a reference molecule, but that differs structurally from the reference molecule. For example, a variant polypeptide or nucleic acid may differ from a reference polypeptide or nucleic acid as a result of one or more differences in amino acid or nucleotide sequence and / or one or more differences in the chemical moieties (e.g., carbohydrates, lipids, phosphate groups) that are covalent components of the polypeptide or nucleic acid (e.g., to which the polypeptide or nucleic acid backbone is attached). DETAILED DESCRIPTION OF THE INVENTION

[0159] I. Malaria Malaria is a mosquito-borne infectious disease caused by the unicellular eukaryotic Plasmodium parasite transmitted by the bite of Anopheles spp. mosquitoes (Phillips, M., et al. Malaria. Nat Rev Dis Primers 3, 17050 (2017), which is incorporated herein by reference in its entirety. Mosquitoes that transmit malaria must be infected through a previous blood meal taken from an infected subject (e.g., a human). When a mosquito bites an infected subject, a small amount of blood containing the malaria parasite is collected. The infected mosquito can then subsequently bite an uninfected subject and infect the subject.

[0160] Malaria remains one of the most serious infectious diseases, causing approximately 200 million clinical cases and 500,000 to 600,000 deaths annually. Although significant efforts have been made to develop therapeutic treatments for malaria, many malaria parasites have developed resistance to available treatments. According to the Malaria Eradication Research Agenda Initiative, malaria eradication can only be achieved through effective vaccination.

[0161] In 2015, the European Medicines Agency gave a positive review to a malaria vaccine candidate known as "RTS,S," a milestone in malaria vaccine development. In 2019, the World Health Organization launched a pilot program to provide RTS,S to children at least 5 months of age in parts of three sub-Saharan African countries. RTS,S / AS01 is an adjuvanted protein subunit vaccine consisting of the major repeat region and C-terminal portion of CSP from Plasmodium falciparum fused to hepatitis B surface antigen (HBsAg). The vaccine is a mix of this PfCSP-HBsAg compound and HBsAg, which forms virus-like particles (RTS,S / AS01, Mosquirix™). RTS,S is administered according to a regimen requiring four doses: an initial three-dose schedule given at least one month apart, and a fourth dose 15-18 months after dose three (see, e.g., Vandoolaeghe & Schuerman Expert Rev Vaccines. 15:1481, 2016; PATH_MVI_RTSS_Fact Sheet_042019, which is incorporated herein by reference in its entirety). RTS,S has reportedly been shown to protect approximately 30%-50% of children from clinical disease over an 18-month period. RTS,S has been reported to induce protective antibody and CD4+ T-cell responses, but only negligible CD8+ T-cell responses (see, e.g., Morris et al. Hum Vaccin Immunother 14:17, 2018, which is incorporated herein by reference in its entirety). A phase III trial of RTS,S delivered as a three-dose series with boosters showed moderate vaccine efficacy in children aged 5-17 months after 1 year, preventing 36% of clinical malaria cases over the entire study period, with a median follow-up of 4 years and transmission settings ranging from a high of 20% to a low of 66%.Furthermore, published literature suggests that protection wanes over time, including reports of potential negative efficacy after 5 years in children with high malaria exposure (Olotu et al. 2016, N. Engl. J. Med. 374:2519-29, which is incorporated herein by reference in its entirety). Thus, an effective malaria vaccine is a critical unmet medical need for global health.

[0162] A. Life Cycle During the blood meal, infected mosquitoes inject sporozoites, known as the hepatic stage of Plasmodium spp., along with their anticoagulant saliva. The sporozoites then migrate through the skin into lymphatic vessels and into hepatocytes in the liver. This migration occurs very rapidly and can be completed in just a few minutes (Sinnis et al., Parasitol Int. 2007 Sep;56(3):171-8, incorporated herein by reference in its entirety). This is known to be the bottleneck time in malaria infection, most favorable for therapeutic intervention, because only a small number of sporozoites (thought to be up to several hundred) are injected by the mosquito, and only a small fraction of that number establish an infection in the liver and develop into mature hepatic stage parasites (Flores-Garcia et al., mBio. 2018 Nov 20;9(6):e02194-18, incorporated herein by reference in its entirety). Thus, subjects whose immune systems are primed to clear sporozoites before they enter hepatocytes are able to efficiently clear the infection.

[0163] One particular challenge associated with clearing malaria infection during this bottleneck is that the most abundant and immunogenic protein on the sporozoite surface, the circumsporozoite protein (CSP), is exposed to the immune system in small amounts and for only a short time due to the variably low inoculum from the mosquito and the kinetics of hepatocyte infection after inoculation. After liver infection is established, parasites no longer express CSP and instead differentiate into stages with a different mosaic of surface antigens. Furthermore, due to the bivalency of antibodies and the density and proximity of adjacent CSPs on the surface of the bound parasite, antibody binding to CSPs can result in a phenomenon called CSP precipitation, whereby antibodies can crosslink adjacent CSPs, precipitating them and causing them to fall off the parasite surface, leaving a trail of precipitated, antibody-bound CSPs that the parasite can replace during its normal CSP translocation process (Livingstone et al., Sci Rep 11, 5318 (2021); Steward et al., J Protozool. 1991 Jul-Aug;38(4):411-21, which are incorporated herein by reference in their entireties).

[0164] As they migrate from the skin inoculation site to the liver, sporozoites traverse host cells (Mota et al., Science 2001 Jan 5;291(5501):141-4, which is incorporated herein by reference in its entirety). To gain access to hepatocytes, sporozoites traverse different types of host cells in the dermis, including fibroblasts and phagocytes (Amino et al., Cell Host Microbe. 2008 Feb 14;3(2):88-96, which is incorporated herein by reference in its entirety), and the liver sinusoidal barrier, which contains liver endothelial cells and Kupffer cells (Frevert et al., PLoS Biol 3(6):e192.2005, which is incorporated herein by reference in its entirety), and sinusoidal endothelial cells (Tavares et al., J Exp Med 2013 May 6;210(5):905-15, which is incorporated herein by reference in its entirety). Sporozoites preferentially traverse cells with low-sulfated heparan sulfate proteoglycans (HSPGs), but preferentially invade cells with high-sulfated HSPGs (Coppi et al., Cell Host & Microbe 2, 316-327, November 2007, which is incorporated herein by reference in its entirety).

[0165] Cell crossing was first observed as the non-phagocytic entry of P. berghei sporozoites into macrophages, followed by "escape" from these cells (Vanderberg et al., J. Euk. Microbiol. 37:528-536, 1990, which is incorporated herein by reference in its entirety. The biochemical, biophysical, and stepwise processes of crossing are still being studied. However, electron microscopy suggests that host cell destruction occurs upon entry and exit from the host cell (Mota et al., 2001; Tavares et al., 2013, which is incorporated herein by reference in its entirety). It has also been shown that P. yoelii sporozoites can enter hepatocytes via transient vacuoles, and that host membrane destruction occurs upon exit from the cell, rather than upon entry (Risco-Castillo et al., Cell Host Microbe 2015 Nov 11;18(5):593-603, which is incorporated herein by reference in its entirety).

[0166] Sporozoites also traverse hepatocytes before establishing a productive hepatocyte infection (Mota et al., 2001, which is incorporated herein by reference in its entirety). Several possibilities have emerged as to why this occurs. The first hypothesis suggested that translocation through hepatocytes primes the parasite for invasion by activating apical exocytosis (Mota et al., Nat Med 2002 Nov;8(11):1318-22, which is incorporated herein by reference in its entirety. The second theory suggested that traversal releases hepatocyte growth factor (HGF), making adjacent hepatocytes more susceptible to infection (Carrolo et al., Nat Med. 2003 Nov;9(11):1363-9, which is incorporated herein by reference in its entirety). Finally, other studies suggest that it takes time for sporozoites to turn off the machinery for traversal and activate the invasion machinery (Amino et al., 2008; Coppi et al., 2007, which are incorporated herein by reference in their entirety), and that traversal functions primarily to penetrate the cellular barrier and evade phagocytosis on the way to the liver (Amino et al., 2008). al., 2008, Coppi et al., 2007, Tavares et al., 2013, which are incorporated herein by reference in their entireties).

[0167] Although sporozoites have been shown to traverse human cells (Behet et al., Malar J 2014 Apr 5;13:136; Cha et al., J Exp Med 2015 Aug 24;212(9):1391-403; Dumoulin et al., PLoS One 2015 Jun 12;10(6):e0129623; van Schaijk et al., PLoS ONE,3(10).e3549 2008, which are incorporated by reference in their entireties), the molecular basis for the traversal process has remained largely unexplored. Antibodies against circumsporozoite proteins (CSPs) impair traversal (Dumoulin et al., 2015, incorporated herein by reference in their entirety), but this is likely due to inhibition of motility rather than a direct effect (Cha et al., J Exp Med 2016 Sep 19;213(10):2099-112, incorporated herein by reference in their entirety). Furthermore, antibodies induced by chloroquine prophylaxis with sporozoites interfere with cell traversal, and these may also target CSPs (Behet et al., 2014). Recently, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the parasite surface has been shown to interact with CD68 on Kupffer cells during traversal (Cha et al., 2015, Cha et al., 2016, incorporated herein by reference in their entirety).

[0168] In rodent malaria parasites such as P. berghei, two sporozoite microneme proteins that appear to be essential for cell crossing have been identified (SPECT1; Ishino et al., PLoS Biol., 2 (2004), pp. 77-84) and SPECT2 (Ishino et al., Cell. Microbiol., 7 (2005), pp. 199-208), also referred to as perforin-like protein 1 (PLP1) (Kaiser et al., Mol. Biochem. Parasitol., 133 (2004), pp. 15-26), which are incorporated herein by reference in their entireties). Genetic disruption of SPECT1 or SPECT2 rendered sporozoites unable to cross mouse cells, yet they still invaded hepatocytes in vitro (Ishino et al., 2004; Ishino et al., 2005, which are incorporated herein by reference in their entireties). When injected into rodents, sporozoites lacking SPECT1 or SPECT2 were impaired for liver infection, although a small number of sporozoites still established liver infection and resulted in subsequent patency. However, deletion of Kupffer cells enabled the mutants to establish liver infection at levels comparable to wild-type parasites (Ishino et al., 2004; Ishino et al., 2005, which are incorporated herein by reference in their entireties). This data suggests that traversal by sporozoites infecting rodents is important for navigating through the sinusoidal layer but not for hepatocyte invasion, malarial exoerythrocytic development, or intraerythrocyte growth (Ishino et al., 2004; Ishino et al., 2005, which are incorporated herein by reference in their entireties).

[0169] The ortholog of SPECT2 in P. yoelii, PLP1, has been shown to play a role in cell traversal. This protein is not required for hepatocyte entry, but plays a role in release from transient vacuoles during traversal (Risco-Castillo et al., 2015, which are incorporated herein by reference in their entirety). Thus, sporozoites that infect rodents can traverse host cells by generating vacuoles during the entry step and can use perforin-like proteins (e.g., SPECT2 / PLP1) to escape from this compartment and / or the host cell during cell egress.

[0170] Once sporozoites invade hepatocytes, they differentiate into merozoites, a replicative form of the parasite that can lyse hepatocytes after multiple rounds of replication. Within a few days, hundreds of sporozoites can become hundreds of thousands of merozoites. When infected hepatocytes rupture, they release merozoites into the bloodstream, where they invade red blood cells and initiate the asexual reproductive stage, the symptomatic stage of the disease. Within a few days, millions of merozoites can be present in the blood.

[0171] Malaria symptoms typically develop 4–8 days after initial red blood cell invasion. The merozoite replication cycle within the red blood cell continues for 36–72 hours until hemolysis, releasing merozoites for another round of red blood cell infection. Thus, in synchronous infections (infection resulting from a single infectious bite), fever occurs every 36–72 hours as infected red blood cells lyse and release large amounts of endotoxin.

[0172] Plasmodium spp. parasites gain entry into red blood cells through specific ligand-receptor interactions mediated by proteins on the parasite surface that interact with receptors on host erythrocytes (mature red blood cells) or reticulocytes (immature red blood cells). P. falciparum can invade and replicate in both erythrocytes and reticulocytes, while P. vivax and other species primarily invade reticulocytes, which are less abundant than erythrocytes. While most erythrocyte- or reticulocyte-binding proteins associated with invasion are redundant or expressed as families of variant forms, two essential erythrocyte receptors have been identified for P. falciparum: basigin and complement decay-accelerating factor (CD55).

[0173] Plasmodium vivax and Plasmodium ovale can also enter a dormant state, or hypnozoite, in the liver.

[0174] Merozoites released from red blood cells invade other red blood cells and continue replicating, or in some cases, differentiate into male or female gametocytes. Gametocytes concentrate in skin capillaries and are then taken up by mosquito vectors in another blood meal. Within the mosquito gut, each male gametocyte forms eight male gametes after three mitotic divisions, and female gametocytes mature into female gametes. The male gametes are flagellated, motile forms that seek female gametes. The male and female gametocytes fuse to form diploid zygotes, which elongate into ookinetes. This motile form secretes chitinase, enters the surrounding trophoblast, migrates across the midgut epithelium to the basolateral side of the midgut, and anchors to the basement membrane as an oocyst. The oocysts mature over 14–15 days, undergo a replicative cycle, and form sporozoites, which are eventually released into the hemocoel. The hemocoel is a sugar- and substrate-rich environment favorable for parasite survival. Thousands of sporozoites can form from a single oocyst and distribute randomly throughout the hemocoel. These sporozoites are motile, rapidly rupture the hemolymph, and only approximately 20% successfully invade the salivary glands. Following salivary gland invasion, sporozoites are reprogrammed through an unknown mechanism to prepare for liver invasion. Evidence for this reprogramming is also demonstrated by the inability of midgut sporozoites (directly from the oocyst) to invade hepatocytes and the fact that sporozoites that successfully invade salivary glands are unable to reinvade other salivary glands if presented with one. Salivary gland sporozoites alter mosquito behavior and salivary gland function due to reduced saliva production, leading to increased mosquito probing behavior and increasing the likelihood of transmission to a human host via mosquito bite.

[0175] Some drugs that prevent the invasion or proliferation of Plasmodium spp. in the liver have prophylactic activity, drugs that block the erythrocytic stage are necessary to treat the symptomatic phase of the disease, and compounds that inhibit gametocyte formation or its development in mosquitoes (including drugs that kill blood-feeding mosquitoes) are transmission-blocking agents (Phillips, et al. Malaria. Nat Rev Dis Primers 3, 17050 (2017), which is incorporated herein by reference in its entirety).

[0176] B. Genome Since the first sequence of the P. falciparum 3D7 genome was completed in 2002, genomic research on malaria parasites has progressed rapidly. Except for a brief diploid phase following fertilization in the mosquito midgut, Plasmodium parasites are haploid throughout their life cycle. The genomes of different species range from 20 to 35 megabases and contain 14 chromosomes, a roughly 35-kb circular plasmid genome, and multiple copies of 6-kb mitochondrial DNA. Comparison of genomes from different species has shown that homologous genes are often found in composite blocks arranged in different orders among different chromosomes.

[0177] The adenine-thymine (AT) content of Plasmodium spp. can also vary greatly, ranging from approximately 80% AT in P. falciparum, P. reichenowi, and P. gallinaceum to approximately 75% AT in rodent malaria parasites and approximately 60% AT in P. vivax, P. knowlesi, and P. cynomolgi. AT content is often higher in introns and intergenic noncoding regions than in protein-coding exons, averaging 80.6% AT across the P. falciparum genome compared with 86.5% in noncoding sequences. The high AT content of P. falciparum reflects numerous low-complexity regions, simple sequence repeats, and microsatellites, as well as highly skewed codon usage bias. Polymorphisms in AT-rich repeats provide rich markers for linkage mapping of drug resistance genes and tracking the evolution and structure of parasite populations.

[0178] The malaria parasite genome contains a multigene family that plays important roles in parasite interactions with the host, including antigenic variation, signal transduction, protein transport, and adhesion. Among these gene families, the gene encoding P. falciparum erythrocyte membrane protein 1 (PfEMP1) has been most extensively studied. Individual P. falciparum parasites carry a unique set of 50–150 copies of var genes within their genome, where gene expression switches can generate antigenic variation. PfEMP1 plays a key role in the pathogenesis of clinical manifestations such as cerebral malaria and placental malaria by mediating cytoadhesion of infected red blood cells (iRBCs) in deep tissues. Different PfEMP1 molecules bind to various host molecules, including α2-macroglobulin, CD36, chondroitin sulfate A (CSA), complement 1q, CR1, E-selectin and P-selectin, endothelial protein C receptor (EPCR), heparan sulfate, ICAM1, IgM, IgG, PECAM1, thrombospondin (TSP), and VCAM1. Such binding leads to the activation of various host inflammatory responses. Hemoglobin abnormalities, including hemoglobin C and hemoglobin S phenotypes, prevent the display of PfEMP1 on the knob structure of iRBCs. This insufficient display of PfEMP1 on the host cell surface provides protection against malaria by reducing cell adhesion and activation of inflammatory processes that promote the development of severe disease.

[0179] Members of the large Plasmodium interspersed repeat (pir) multigene family have different names depending on the parasite species, e.g., yir in P. yoelii, bir in P. berghei, and vir in P. vivax. Several P. falciparum gene families (stevor, rif, and PfMC-2™) are classified under pir due to their similar gene structure, characteristically containing a short first exon, a long second exon, and a third exon encoding a transmembrane domain. Recent studies have shown that the pir gene from P. chabaudi (cir) is expressed in different cellular locations within and on the surface of iRBCs, as well as in merozoites. Malaria parasites dedicate a large portion of their genome to gene families that ensure evasion of host immune defenses and the protection of molecular processes essential for infection. Despite the inherent difficulties in investigating these families, the importance of studying their role in parasite-host interactions and virulence is emphasized.

[0180] Additional exemplary polymorphic gene families include 14 gene families encoding proteins with six cysteines (6-Cys). These proteins are often localized on the parasite surface where they interact with host proteins and are expressed during various parasite developmental stages. 6-Cys proteins also exhibit diverse functions, such as playing roles in parasite fertilization, mating interactions, evasion of immune responses, and invasion of hepatocytes. Proteins expressed during the asexual stage are generally polymorphic and / or under selection, suggesting they may be targets of the host immune response; however, their function in parasite development remains largely unknown.

[0181] The Plasmodium genome can be highly polymorphic. Early studies demonstrated polymorphism involving tens to hundreds of kilobases, indicating that the chromosomal structure of P. falciparum is largely conserved in the central region, but that there is extensive polymorphism in both length and sequence near the telomeres. Much of the subtelomeric variation was explained by recombination within blocks of repeat sequences and gene families.

[0182] The frequency of simple sequence repeats (microsatellites) in P. falciparum is estimated to be approximately one polymorphic microsatellite per kb of DNA. Without intending to be bound by any one theory, this high rate may reflect the AT-rich nature of the genome. Microsatellites appear to be less frequent in other Plasmodium species, which have genomes with lower AT content. In addition to the highly polymorphic and repetitive structure of the Plasmodium genome, there are also numerous single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) (Su et al., Plasmodium Genomics and Genetics: New Insights into Malaria Pathogenesis, Drug Resistance, Epidemiology, and Evolution. Clin Microbiol Rev. 2019 Jul 31;32(4), which is incorporated herein by reference in its entirety).

[0183] C. Plasmodium proteins Plasmodium parasites are known to express a variety of proteins at different stages of their life cycle. Exemplary Plasmodium proteins are described below, and exemplary amino acid sequences are shown in Table 2.

[0184] Circumsporozoite proteins (CSPs) are multifunctional proteins involved in the Plasmodium life cycle because they are required for sporozoite formation in the mosquito midgut, sporozoite release from oocysts, invasion of salivary glands, sporozoite attachment to hepatocytes in the liver, and sporozoite invasion of hepatocytes (see, e.g., Zhao et al. (2016) PLoS ONE 11(8):e0161607). CSPs are present in all Plasmodium species, and although there is variation in amino acid sequence across species, the overall domain structure of the central repeat and non-repetitive flanking regions is well conserved (see, e.g., Zhao et al. (2016) PLoS ONE 11(8):e0161607; Wahl et al. (2016) PLoS ONE 11(8):e0161607). See, e.g., UniProt accession numbers A0A2L1CF52, A0A2L,1CF88, C6FGZ3, C6FH2, 7C6FHG7, M1V060, M1V0A3, M 1V0B0, M1V0C4, M1V0E0, M1V9I4, M1VFN9, M1VKZ2, P02893, Q5EIJ9, Q5EIK2, Q5EIK8, Q5EIL3, Q5EIL5, Q5EIL8, Q5R2L2, Q7K740, Q8I9G5, Q8I9J3, Q8I9J4), Table 1 includes exemplary sequences of CSP P. falciparum isolates from Asia, South America, and Africa. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7]

[0185] An exemplary CSP amino acid sequence is provided in SEQ ID NO:1.

[0186] RH5 is found in Plasmodium falciparum (P. falciparum) but not in other species of Plasmodium that infect humans. RH5 orthologs are also found in other species belonging to the subgenus Lavarenia, including parasites that infect chimpanzees and gorillas, demonstrating a unique role in P. falciparum invasion of human erythrocytes. See, e.g., Ragotte, et al. Trends Parasitol. 36(6) 2020, incorporated herein by reference in its entirety. RH5 is expressed during the mature schizont stage and can complex with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (Ripr) to form an elongated protein trimer on the merozoite surface that binds to the erythrocyte surface protein basigin. See, e.g., Ragotte Trends Parasitol 2020 Jun;36(6):545-559, incorporated herein by reference in its entirety.

[0187] In humans, RH5 binding to basigin plays a key role in invasion, acting downstream of membrane deformation. RH5 binding to basigin is required to induce calcium spikes within red blood cells, which are blocked when merozoites attempt invasion in the presence of anti-RH5, anti-Ripr, or anti-basigin antibodies or soluble basigin. See, for example, Ragotte (2020).

[0188] RH5 is a 63 kDa protein expressed at the mature schizont stage. It is cleaved into a 45 kDa form that is processed and shed by the parasite. The structure of PfRH5 reveals a kite-like architecture formed by two three-stranded helical bundles brought together. See, for example, Ragotte (2020).

[0189] The RH5 sequence is known (e.g., UniProt accession numbers A0A159SK44, A0A159SK99, A0A159SKS8, A0A159SKW8, A0A159SL23, A0A159SL78, A0A159SL96, A0A159SLM7, A0A159SMC8, A0A159SMR9, A0A161FQT0, A0A1B1UZE2, A0A1B1 UZE4, A0A1B1UZE5, A0A346RCI1, A0A346RCJ0, A0A346RCJ2, A0A346RCJ3, A0A346RCJ4, A0A346RCK4, A0A346RCK5, A0A346RCK6, A0A346RCK9, B2L3N7, Q8IFM5), an exemplary RH5 amino acid sequence is provided in SEQ ID NO: 365.

[0190] P113 is a glycosylphosphatidylinositol (GPI)-linked protein that directly interacts with the N-terminus of unprocessed RH5, providing a mechanism by which the RH5 invasion complex is tethered to the merozoite surface. See, for example, Ragotte (2020). P113 orthologs have been found in all Plasmodium species sequenced to date, suggesting common and conserved function(s) (Bullen et al. (2022) Molecular Microbiology 117:1245-1262, incorporated herein by reference in its entirety). Nevertheless, in a rodent model of malaria, P. berghei, p113 knockout parasites were viable, indicating that the protein was not essential for asexual blood-stage growth and invasion. However, knockout parasites exhibit defects in natural sporozoite transmission, leading to delayed patency in infected mice (Offeddu et al. (2014) Mol. Biochem. Parasitology 193:101-109, which is incorporated herein by reference in its entirety).

[0191] The Plasmodium P113 sequence is known (see, e.g., Uniprot accession number Q8ILP3). An exemplary P113 amino acid sequence is provided in SEQ ID NO:326.

[0192] Cysteine-rich protective antigen (CyRPA) is a 43 kDa protein with a predicted N-terminal secretion signal. CyRPA is part of a multiprotein complex that includes RH5 and Ripr, and secretes Ca. 2+ PfCyRPA is highly conserved with only a single SNP at a prevalence of over 5%, is essential for invasion (since conditional knockdown causes loss of invasive activity), and exhibits poor serological reactivity from natural exposure (see, e.g., Ragotte (2020)).

[0193] Plasmodium CyRPA sequences are known (see, e.g., Uniprot accession numbers A0A2S1Q7P0, A0A2S1Q7P5, A0A2S1Q7Q4, Q8IFM8). An exemplary CyRPA amino acid sequence is provided in SEQ ID NO: 329.

[0194] RH5-interacting protein (Ripr) is an approximately 120 kDa protein that localizes to micronemes during the schizont stage of the P. falciparum life cycle. The full-length 120 kDa protein is processed into two similarly sized fragments: an N-terminal fragment (containing EGF domains 1 and 2) and a C-terminal fragment (containing EGF domains 3–10). Ripr colocalizes with RH5 and CyRPA during parasite invasion at the junction between merozoites and erythrocytes. Parasites with a conditional knockout of PfRipr induce membrane deformation but are unable to complete invasion (see, e.g., Ragotte (2020)).

[0195] Plasmodium Ripr sequences are known (see, e.g., UniProt accession numbers A0A193PDI9, A0A193PDK3, A0A193PDK8, A0A193PDL3, A0A193PDL9, A0A193PDP4, A0A193PDQ8, A0A193PE01, A0A193PE05, A0A193PE07, O97302, A0A193PE17). An exemplary Ripr amino acid sequence is provided in SEQ ID NO:332.

[0196] E140 is found in all Plasmodium species for which genome sequences are available and is well conserved, with amino acid identity ranging from 34 to 92% between species. See, for example, Smith, et al. PLoS One 15.5 (2020):e0232234, http: / / doi:10.1371 / journal.pone.023223, and U.S. Patent Application Publication No. US2019 / 0117752, which are incorporated by reference in their entireties. E140 is also highly conserved (95 to 99%) among P. falciparum strains isolated from different locations around the world and exhibits low mutation frequencies. E140 is expressed at different stages of the malaria parasite life cycle (specifically, E140 has been detected in sporozoite, hepatic, and blood-stage parasites).

[0197] Protein structure algorithms predict that the E140 protein has five transmembrane domains that may span membranes of either parasite or host origin. E140 shows distinct patterns of protein expression at the mature sporozoite, late hepatic, and late schizont stages. It transports to the anterior and posterior ends of sporozoites, the parasitophorous space at the late hepatic stage, and around developing merozoites at the late schizont stage. It is also known to be expressed in mature salivary gland sporozoites and oocyst-derived sporozoites and oocysts.

[0198] The E140 sequence is known (see, e.g., UniProt accession numbers A0A650D649, A0A650D653, A0A650D672, A0A650D687, A0A650D690, A0A650D694, A0A650D6A3, A0A650D6B8, A0A650D6L3, A0A650D6L7, Q8I299), and an exemplary E140 amino acid sequence is provided in SEQ ID NO:335.

[0199] CelTOS is required for sporozoite traversal through Kupfer cells during the liver invasion process. CelTOS forms pores from within the cell, allowing sporozoites to be released into the liver. Antibody epitopes have been characterized from immunized mice and infected human populations (Pf and Pv). Mouse studies have shown that immunization with CelTOS provides protection and protection against challenge. Vaccination with CelTOS can generate antibodies that bind to the extracellular domain of the pore-forming complex, block complete pore formation, and prevent sporozoite traversal to the liver. See, e.g., Jimah et al., Elife 2016 Dec 1;5:e20621.doi:10.7554 / eLife.20621, which is incorporated herein by reference in its entirety.

[0200] Plasmodium CelTOS sequences are known (see, e.g., Uniprot accession numbers M1ETJ8, Q53UB7, A0A2R4QLA5, A0A2R4QLI0, A0A2R4QLI5, A0A2R4QLJ1, A0A2R4QLJ4, M1ETJ8, Q53UB8, Q8I5P1). An exemplary CelTOS amino acid sequence is provided in SEQ ID NO:350.

[0201] SPECT1 and SPECT2 (the latter sometimes referred to as perforin-like protein 1 (PLP1)) are essential Plasmodium proteins that may play a role in cell traversal. See Yang et al., Cell Rep. 2017 Mar 28;18(13):3105-3116. doi:10.1016 / j.celrep.2017.03.017, which is incorporated herein by reference in its entirety. Targeted disruption of P. falciparum SPECT1 or SPECT2 has been shown to reduce sporozoite infectivity in the development of the hepatic stage in humanized mice. However, the mechanism of cell traversal of these two proteins has not yet been defined in P. falciparum. See Yang et al.

[0202] SPECT1 and SPECT2 are considered attractive pre-erythrocytic immune targets due to the important role they are thought to play in the crossing of malaria parasites across the dermis and liver sinusoidal wall prior to hepatocyte invasion. Recombinant P. falciparum SPECT2, as well as the MACPF / CDC domain of PfSPECT2, binds Ca. 2+ PfSPECT2 has been shown to cause lysis of red blood cells in a Ca2+-dependent manner. PfSPECT2 is also involved in the Ca2+-dependent release of P. falciparum merozoites from red blood cells.

[0203] Plasmodium SPECT1 and SPECT2 sequences are known (see, e.g., UniProt accession numbers Q8IDR4 and Q9U0J9), and exemplary amino acid sequences are provided in SEQ ID NOs: 353 and 356, respectively.

[0204] Export protein 1 (EXP1) is a single-pass transmembrane protein with an N-terminal signal peptide that is expressed during the intraerythrocytic and hepatic stages (see, e.g., Spielmann et al., Int J Med Microbiol. 2012 Oct;302(4-5):179-86, which is incorporated herein by reference in its entirety). EXP1 has been shown to initially localize to dense granules in merozoites and then transport to the parasitophorous vacuole membrane (PVM) after invasion (see, e.g., Iriko et al., Parasitol Int. 2018 Oct;67(5):637-639, which is incorporated herein by reference in its entirety). Once localized to the PVM, EXP1 forms a homo-oligomer with its N-terminus exposed to the parasitophorous vacuole lumen and its C-terminus exposed to the erythrocyte cytoplasm (see, e.g., Mesen-Ramirez et al., PLoS Biol. 2019 Sep 30;17(9):e3000473, which is incorporated herein by reference in its entirety).

[0205] EXP1 has been demonstrated to have glutathione S-transferase (GST) activity that can protect Plasmodium from oxidative damage (see, e.g., Mesen-Ramirez et al., PLoS Biol 17(9) 2019 Sep 30;17(9):e3000473, which is incorporated herein by reference in its entirety). Recently, it has been demonstrated that EXP1 is important for Plasmodium survival by maintaining the correct localization of EXP2, a nutrient-permeable channel within the PVM (see, e.g., Mesen-Ramirez et al., 2020).

[0206] The P. falciparum EXP1 polypeptide sequence is known (see, e.g., UniProt Accession Nos. Q8IIF0, W7JTD3, Q25840, Q548U2, Q5VKK2, Q5VKK5, Q5WRH8, Q6V9G4, Q6V9G6, Q6V9G9, Q6V9H1, Q6V9H2, Q9U590, P04923, P04926). An exemplary EXP1 amino acid sequence is provided in SEQ ID NO:314.

[0207] The infectious sporozoite gene 3 (UIS3) upregulated protein is a membrane-bound protein that localizes to the sporozoite parasitophorous membrane (PVM) in infected hepatocytes. UIS3 has been shown to interact with liver fatty acid-binding protein (L-FABP) and to be involved in fatty acid and / or lipid import during Plasmodium growth (see, e.g., Sharma et al., J Biol Chem. 2008 Aug 29;283(35):24077-24088; Mikolajczak et al., Int J Parasitol. 2007 Apr;37(5):483-9, which are incorporated herein by reference in their entireties).

[0208] Sporozoite invasion of host hepatocytes is followed by synthesis of key Plasmodium structural features (e.g., the parasitophorous vacuole membrane). During the hepatocyte stage, Plasmodium relies on host fatty acids for rapid synthesis of its membrane (see, e.g., Sharma et al., J Biol Chem. 2008 Aug 29;283(35):24077-24088, which is incorporated herein by reference in its entirety). UIS3 insertion into the PVM provides Plasmodium with a way to import essential fatty acids and / or lipids during the rapid sporozoite growth phase (see, e.g., Sharma et al., 2008).

[0209] Immunization with UIS3-deficient Plasmodium berghei sporozoites protects against malaria in rodent malaria models (see, e.g., Mueller et al., Nature. 2005 Jan 13;433(7022):164-7, which is incorporated herein by reference in its entirety). Although UIS3-deficient Plasmodium berghei can initiate the transformation process in the liver, they exhibit severe defects during transformation to trophozoites (see, e.g., Mueller et al., 2005). UIS3-deficient Plasmodium berghei also fail to develop into mature liver schizonts, thus aborting malaria infection within the liver itself (see, e.g., Mueller et al., 2005). Furthermore, it was previously demonstrated that UIS3 from Plasmodium berghei and UIS3 from Plasmodium falciparum exhibited low (i.e., 34%) amino acid sequence identity (see, e.g., Mueller et al., 2005).

[0210] Plasmodium UIS3 sequences are known (see, e.g., UniProt accession numbers A0A509ARS3, A0A1C6YLP3, Q8IEU1, A0A384KLI1, A0A1G4H423, A0A077YB01, Q9NFU4). An exemplary UIS3 amino acid sequence is provided in SEQ ID NO: 359.

[0211] Upregulated infectious sporozoite gene 4 (UIS4) contains a single transmembrane domain and localizes to secretory organelles of sporozoites and the parasitophorous vacuole membrane (PVM) of liver stage sporozoites. UIS4 is not expressed in blood stage or early sporozoites produced in oocysts (see, e.g., Mackellar et al., Eukaryot Cell. 2010 May;9(5):784-794, which is incorporated herein by reference in its entirety).

[0212] Deletion of the UIS4 gene is associated with a block in the development of early liver disease stages (see, e.g., Vaughan and Kappe, Cold Spring Harb Perspect Med. 2017 Jun 1;7(6):a025486, which is incorporated herein by reference in its entirety. Recently, UIS4 has been demonstrated to be involved in Plasmodium berghei survival by evading host actin structures deployed as part of the host cytoplasmic defense (see, e.g., Bana et al., iScience. 2022 Apr 22;25(5):104281. doi:10.1016 / j.isci.2022.104281.eCollection 2022 May20, which is incorporated herein by reference in its entirety). P. falciparum inhibits the growth of P. yoelii It has an orthologue to UIS4 named ETRAMP10.3 that is unable to function as a functional complement to UIS4, indicating that it likely serves a different function in the P. falciparum life cycle (see Mackellar et al., Eukaryot. Cell 9:784-94 (2010) which is incorporated herein by reference in its entirety).

[0213] Plasmodium falciparum early transcribed membrane protein 10.3 (ETRAMP10.3) is an approximately 10 kDa protein conserved across Plasmodium species and a member of a multigene family of early transcribed membrane proteins, including proteins located in the parasitophorous vacuole. Some ETRAMP proteins are specific to P. falciparum and are not found in Plasmodium species that infect other organisms. ETRAMP10.3 is an example of an ETRAMP protein expressed in both liver and blood-stage P. falciparum parasites. ETRAMP10.3 transcription has been found to peak during the transition from the ring to the trophozoite stage of P. falciparum blood-stage infection in human hosts. ETRAMP10.3 is localized to the parasitophorous vacuole and exported to host erythrocytes during blood-stage infection. ETRAMP10.3 is sometimes referred to as upregulated in infectious sporozoite gene 4 (UIS4), but ETRAMP10.3 is understood to be an ortholog of UIS4 based on similarity and structural similarity. However, ETRAMP10.3 is not a functional ortholog of UIS4 and may play a different biological role. While the biological function of ETRAMP10.3 has not yet been fully resolved, its localization to vesicular structures within host erythrocytes suggests a role in host-parasite interactions or in the remodeling of infected erythrocytes. ETRAMP10.3 appears to play an important role in the Plasmodium life cycle. Deletion of ETRAMP10.3 can lead to aborted liver stage development and progression to the asexual blood stage in mice.

[0214] Although in the literature the terms "UIS4" and "ETRAMP10.3" are sometimes used to refer to different proteins, in the context of the present disclosure the terms "UIS4" and "ETRAMP10.3" are used interchangeably to refer to ETRAMP10.3.

[0215] The Plasmodium ETRAMP10.3 sequence is known (see, e.g., UniProt Accession No. Q8IJM9, which is incorporated herein by reference in its entirety). An exemplary ETRAMP10.3 amino acid sequence is provided in SEQ ID NO:362.

[0216] Liver-specific protein 1 (LISP-1) is expressed in hepatocytes during Plasmodium pathogenesis and localizes to the parasitophorous vacuole membrane (PVM) (e.g., Ishino et al., Cell Microbiol. 2009 Sep;11(9):1329-1339). LISP-1 is expressed at high levels during late liver stage development and has been shown to be involved in PVM degradation and subsequent merozoite release (see, e.g., Ishino et al., Cell Microbiol. 2009 Sep;11(9):1329-1339, which is incorporated herein by reference in its entirety).

[0217] Intracellular Plasmodium lacking LISP-1 develop into hepatic merozoites and exhibit normal infectivity for erythrocytes (see, e.g., Ishino et al., Cell Microbiol. 2009 Sep;11(9):1329-1339, which is incorporated herein by reference in its entirety). However, LISP1-deficient liver-stage Plasmodium do not rupture the PVM and remain trapped within hepatocytes (see, e.g., Ishino et al., 2009).

[0218] The Plasmodium LISP-1 sequence is known (see, e.g., UniProt accession numbers A0A2I0C2X6, Q8ILR5). An exemplary LISP-1 amino acid sequence is provided in SEQ ID NO: 308.

[0219] Liver-specific protein 2 (LISP-2) contains a modified 6-cys domain and is expressed during Plasmodium development in hepatocytes (see, e.g., Orito et al., Mol Microbiol. 2013 Jan;87(1):66-79, which is incorporated herein by reference in its entirety). LISP-2 has been shown to be expressed by hepatic-stage Plasmodium, exported into hepatocytes, and distributed throughout the host cell, including the nucleus (see, e.g., Orito et al., 2013).

[0220] Intracellular Plasmodium lacking LISP2 do not mature efficiently during merozoite development (see, e.g., Orito et al., 2013).

[0221] Plasmodium LISP-2 sequences are known (see, e.g., UniProt accession numbers A0A2I0BZR4, Q8I1X6, Q9U0D4). An exemplary LISP-2 amino acid sequence is provided in SEQ ID NO: 311.

[0222] Thrombospondin-related adhesion proteins (TRAPs) contain an N-terminal domain, commonly referred to as the von Willebrand factor A domain, which binds Mg, required for sporozoite motility in vitro and infection in vivo. 2+It is most similar to the integrin I domain because it contains a metal ion-dependent adhesion site (MIDAS) with an ion (see, e.g., Lu et al., PLoS One. 2020;15(1):e0216260, which is incorporated herein by reference in its entirety). The I domain is inserted into an extendable β-ribbon, followed by a thrombospondin repeat (TSR) domain, a C-terminal proline-rich segment, a single-pass transmembrane domain, and a cytoplasmic domain (see, e.g., Lu et al., 2020). Sequence analysis of the proline-rich segment revealed the presence of an SH3 domain-binding PxxP motif in Plasmodium TRAP (Akhouri et al., Malar J. 2008 Apr 22;7:63. doi:10.1186 / 1475-2875-7-63, which is incorporated herein by reference in its entirety).

[0223] TRAP is conserved in the micronemes and becomes surface-exposed at the sporozoite tip when the parasite contacts the host cell (Akhouri et al., Malar J. 2008 Apr 22;7:63. doi:10.1186 / 1475-2875-7-63, which is incorporated herein by reference in its entirety. TRAP also plays an important role in sporozoite invasion of hepatocytes by assisting sporozoites in gliding motility and recognition of host receptors on mosquito salivary glands and hepatocytes (Akhouri et al., Malar J. 2008 Apr 22;7:63. doi:10.1186 / 1475-2875-7-63, which is incorporated herein by reference in its entirety).

[0224] Plasmodium TRAP sequences are known (see, e.g., UniProt accession numbers A0A5Q2EXK8, A0A5Q2EZD7, A0A5Q2F1F6, A0A5Q2F2B8, A0A5Q2F2H6, A0A5Q2F4G9, O76110, P16893, Q01507, Q26020, Q76NM2, W8VNB6), and an exemplary TRAP amino acid sequence is provided in SEQ ID NO: 287.

[0225] Liver stage-associated protein 1 (LSAP-1) has been shown to be found primarily in the periphery of intracellular liver parasites throughout their development, but not in blood-stage parasites, and possibly in trace amounts in salivary gland sporozoites (see, e.g., Siau et al., PLoS Pathog. 2008 Aug 8;4(8):e1000121, incorporated herein by reference in its entirety). LSAP-1 is one of the most abundant transcripts in the salivary gland transcriptome, but has not been detected in proteomic studies of sporozoites. Rather, expression has been detected only in the liver stage (see, e.g., Siau et al., 2008).

[0226] Plasmodium LSAP-1 sequences are known (see, e.g., UniProt accession numbers Q8I632, W7JR53). An exemplary LSAP-1 amino acid sequence is provided in SEQ ID NO:302.

[0227] Like LSAP-1, LSAP-2 is also the most abundant transcript in the salivary gland transcriptome, but has not been detected in proteomic studies of sporozoites. LSAP-2 has shown some efficacy as a vaccine when combined with other antigens. See, e.g., Halbroth et al., Infect Immun. 2020 Jan 22;88(2):e00573-19.doi:10.1128 / IAI.00573-19.Print 2020 Jan 22, which is incorporated herein by reference in its entirety.

[0228] Plasmodium LSAP-2 sequences are known (see, e.g., UniProt accession numbers Q8I632, W7JR53). An exemplary LSAP-2 amino acid sequence is provided in SEQ ID NO:305.

[0229] Liver-stage antigen 1 (LSA-1) is expressed after Plasmodium invades hepatocytes and the antigen accumulates in parasitophorous vacuoles (see, e.g., Tucker, K. et al., 2016, 'Pre-Erythrocytic Vaccine Candidates in Malaria', in AJ Rodriguez-Morales (ed.), Current Topics in Malaria, IntechOpen, London. 10.5772 / 65592, which is incorporated herein by reference in its entirety). The function of LSA-1 remains unknown (see, e.g., Tucker, K. et al., 2016).

[0230] LSA-1 is a 230 kDa pre-erythrocytic protein containing a large central region consisting of more than 80 repeat units of 17 amino acid residues flanked by highly conserved C- and N-terminal regions (Richie, TL and Parekh, FK (2009) Malaria. In Vaccines for Biodefense and Emerging and Neglected Diseases (Barrett, ADT and Stanberry LR, eds), pp. 1309-1364, Elsevier, which is incorporated herein by reference in its entirety). LSA1 is expressed only by hepatic stage Plasmodium, not by sporozoites (Richie, TL and Parekh, FK (2009) Malaria, which is incorporated herein by reference in its entirety). In Vaccines for Biodefense and Emerging and Neglected Diseases (Barrett, ADT and Stanberry LR, eds, pp. 1309-1364, Elsevier, which is incorporated herein by reference in its entirety). Repeat regions result in significant protein variation between strains of Plasmodium falciparum (see, e.g., Tucker, K. et al., 2016).

[0231] Plasmodium LSA-1 sequences are known (see, e.g., UniProt Accession Nos. Q25886, Q25887, Q25893, Q26028, Q9GTX5, O96125). An exemplary LSA-1 amino acid sequence is provided in SEQ ID NO:290.

[0232] Liver stage antigen 3 (LSA-3) is a 200 kDa protein consisting of three non-repeat regions (NR-A, NR-B, and NR-C) flanked by two short repeat regions and one long repeat region (see, e.g., Tucker, K. et al., 2016). The non-repeat regions are well conserved across geographically diverse strains of Plasmodium falciparum (see, e.g., Tucker, K. et al., 2016). The most significant variation is in the repeat regions, which is due to the composition and number of repeat subunits rather than the composition of the repeat regions (see, e.g., Tucker, K. et al., 2016).

[0233] Recently, in vitro data have shown that antibodies against LSA-3 (particularly the C-terminal portion of LSA-3) can provide some protection (see, e.g., Morita et al, Sci Rep. 2017 Apr 5;7:46086. doi:10.1038 / srep46086, which is incorporated herein by reference in its entirety).

[0234] Plasmodium LSA-3 sequences are known (e.g., UniProt accession numbers C7DU21, C7DU22, C7DU23, C7DU24, C7DU25, C7DU26, C7DU27, C7DU28, C7DU29, C7DU32, C7DU33, C7DU34, C7DU36, C7DU37, C7DU38, C7DU39, C7DU40, Q8I042, Q8I0A5, Q8I0D0, Q8IFR1, Q8IFR2, Q8IFR3, Q8IFR4, Q8IFR5, Q8IFR6, Q8IFR7, Q8IFR8, Q8IFR9, Q8IFR10, Q8IFR11, Q8IFR12, Q8IFR13, Q8IFR14, Q8IFR15, Q8IFR16, Q8IFR17, Q8IFR18, Q8IFR19, Q8IFR20, Q8IFR21, Q8IFR22, Q8IFR23, Q8IFR24, Q8IFR25, Q8IFR26, Q8IFR27, Q8IFR28, Q8IFR29, Q8IFR32, Q8IFR33, Q8IFR34, Q8IFR35, Q8IFR36, Q8IFR37, Q8IFR38, Q8IFR39, Q8IFR40, Q8IFR41, Q8IFR42, Q8IFR43, Q8IFR44, Q8IFR45, Q8IFR46, Q8IFR47, Q8IFR48, Q8IFR49, Q8IFR50, Q8IFR51, Q8IFR52, Q8IFR53, Q8IFR54, Q8IFR55, Q8I (See, e.g., 8IFR4, Q8IFR5, Q8IFR6, Q8IFR7, Q8IFR8, Q8IFR9, Q8IFS0, Q8IFS1, Q8IFS2, Q8IFS3, Q8IFS4, Q8IFS5, Q8IFS6, Q8IFS7, Q8IFS8, Q8IFS9, Q8IFT0, Q8IFT1, Q8IFT2, Q8IFT3, Q8IFT4, Q9U0N9, Q9U0P0, A0A2I0BVD6, A0PFM9, O96275.) An exemplary LSA-3 amino acid sequence is provided in SEQ ID NO:299.

[0235] Glutamate-rich protein (GARP) is an 80-kDa protein named for its glutamate-rich amino acid sequence, which comprises 24% of all residues. GARP is primarily expressed in the ring stage and trophozoites and is a nonessential gene in cell culture, but has been shown to be highly immunogenic in animal models (Hon et al., Trends Parasitol. 2020 Aug;36(8):653-655, incorporated herein by reference in its entirety). Although GARP is nonessential in cell culture, its localization to the periphery of infected red blood cells may indicate a role in the sequestration of infected red blood cells. It has been proposed that GARP's involvement in sequestration occurs through binding to the chloride / bicarbonate anion exchanger (Lau et al., PLoS Pathog. 10, e1004135. 2014, incorporated herein by reference in its entirety). Antibodies to GARP have been proposed to serve as an indicator of protection against severe malaria and have shown efficacy in experimental studies in monkeys. See, for example, Hon et al., Trends in Paras 2020 Aug;36(8):653-655.doi:10.1016 / j.pt.2020.05.012 and Laue et al., Plos Path.2014 10,e1004135, which are incorporated herein by reference in their entirety. GARP sequences are known (see, for example, UniProt accession numbers Q9GTW3 and Q9U0N1), and an exemplary GARP amino acid sequence is provided in SEQ ID NO: 341.

[0236] Parasite-infected erythrocyte-specific protein 2 (PIESP2) (see, e.g., UniProt Accession No. Q8I488) is a highly immunogenic protein first expressed in the trophozoite stage and thought to be important for the clinical progression of cerebral malaria. This protein is primarily found within erythrocytes, but has been shown to be present on their surface and can attach to endothelial cells of the brain vasculature. Antibodies against PIESP2 have been shown to prevent Plasmodium vascular attachment and may prove useful in preventing inflammatory responses in the brain and damage to the blood-brain barrier during cerebral malaria progression (see, e.g., Liu et al., Int J Biol Macromol. 2021 Apr 30;177:535-547. doi:10.1016 / j.ijbiomac.2021.02.145, which is incorporated herein by reference in its entirety). The PIESP2 sequence is known (see, eg, UniProt Accession No. Q8I488), and an exemplary PIESP2 amino acid sequence is provided in SEQ ID NO:344.

[0237] Shizont egress antigen-1 (SEA1) is a large 244 kDa protein lacking a transmembrane domain or known targeting signal. While the function of SEA1 is unknown, it has been shown to be effective in rodent vaccine studies and has been proposed as the target of protective antibodies found in children. SEA1 received its name after antibodies against this protein were reported to inhibit the egress of Plasmodium merozoites. SEA1 localizes closely to centromeres during nuclear division, implicating its role in essential processes of replication. To date, various studies have proposed a role for SEA1 not only in egress but also in mitotic division of replicating nuclei. (See, e.g., Perrin et al., mBio. 2021 Mar 9;12(2):e03377-20. doi:10.1128 / mBio.03377-20, which is incorporated herein by reference in its entirety.) The SEA1 sequence is known (see, eg, UniProt Accession No. A0A143ZXM2), and an exemplary SEA1 amino acid sequence is provided in SEQ ID NO:347.

[0238] D. Malaria Sequence Embodiments An exemplary full-length CSP polypeptide amino acid sequence from Plasmodium falciparum isolate 3D7 corresponds to SEQ ID NO: 1 and includes the following: secretion signal (amino acids 1-18), N-terminal domain (amino acids 19-104), junction region (amino acids 93-104), central domain (amino acids 105-272), and C-terminal domain (amino acids 273-397). In exemplary SEQ ID NO: 1, the N-terminal domain includes the N-terminal region (amino acids 19-80), the N-terminal tail region (amino acids 81-92), and junction region (amino acids 93-104). In exemplary SEQ ID NO: 1, the junction region includes the R1 region (amino acids 93-97) and amino acids ADGNPDP (SEQ ID NO: 93) at positions 98-104. In exemplary SEQ ID NO: 1, the central domain includes the minor repeat region (amino acids 105-128) and the major repeat region (amino acids 129-272). In exemplary SEQ ID NO: 1, the minor repeat region includes three repeats of the amino acid sequence NANPNVDP (SEQ ID NO: 477). In exemplary SEQ ID NO: 1, the major repeat region includes 35 repeats of the amino acid sequence NANP (SEQ ID NO: 108), and the 35 repeats of the amino acid sequence NANP are separated into two consecutive stretches, one stretch including 17 repeats of the amino acid sequence NANP and one stretch including 18 repeats of the amino acid sequence NANP adjacent to the amino acid sequence of NVDP (SEQ ID NO: 105). The major repeat region includes the amino acid sequences NPNANP (SEQ ID NO: 111) and NANPNA (SEQ ID NO: 114). In exemplary SEQ ID NO: 1, the C-terminal domain includes a C-terminal region (amino acids 273-375) and a transmembrane domain (amino acids 376-397). In exemplary SEQ ID NO: 1, the C-terminal region includes a Th2R region (amino acids 314-327) and a Th3R region (amino acids 352-363). [Table 2]

[0239] II. Plasmodium T-cell string polypeptide constructs The present disclosure utilizes, among other things, RNA technology as a modality to express one or more Plasmodium T cell string polypeptide constructs (also referred to as "malaria T cell string polypeptide constructs" or "malaria T cell peptide string constructs") that comprise one or more T cell antigens from one or more Plasmodium proteins or one or more portions thereof (e.g., one or more antigenic fragments thereof) described herein. The Plasmodium T cell string polypeptide constructs described herein can comprise one or more T cell antigens from one or more Plasmodium polypeptides or one or more portions thereof (e.g., one or more antigenic fragments thereof) described herein. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more Plasmodium liver stage antigens that elicit a T cell response. As understood in the art, the "T cell antigens" described herein are capable of inducing a T cell response in a subject or model system. In some embodiments, Plasmodium T cell string polypeptide constructs targeted to the liver stage of Plasmodium infection comprise a polypeptide or antigenic portion thereof that is relatively abundant in infected liver cells and is predicted to elicit T cell response(s). The polyribonucleotides described herein encoding Plasmodium T cell string polypeptide constructs, as well as the Plasmodium T cell string polypeptide constructs described herein, are designed to deliver the polypeptide to a subject, where the protein is subsequently degraded and processed for presentation, thereby eliciting an immune response (e.g., T cell response(s)). Methods for determining the presence or absence of a T cell response are well known in the art and are described in the Examples. In a preferred embodiment, the Plasmodium T cell string polypeptide constructs described herein comprise two or more T cell antigens and / or epitopes from a Plasmodium liver stage polypeptide or one or more portions thereof.In some preferred embodiments, the one or more Plasmodium liver stage polypeptides or antigenic portions thereof comprise 2 to 20 liver stage polypeptides or antigenic portions thereof (e.g., antigenic portions that induce a T cell response). In some embodiments, the Plasmodium T cell string polypeptide construct comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, preferably 4, 5, 6, 7, 8, 9, 10, 11, or 12, different liver stage polypeptides or antigenic portions thereof (e.g., each capable of eliciting a T cell response).

[0240] For example, in some embodiments, the Plasmodium T cell string polypeptide construct comprises one or more Plasmodium T cell antigens from CSP, LSA-1(a), LSA-1(b), TRAP, LSAP2, UIS3, ETRAMP10.3, LISP-1, LISP-2, LSA-3, EXP1, LSAP1, and / or polypeptide regions or portions thereof (e.g., one or more antigenic fragments thereof). In some embodiments, the Plasmodium T cell string polypeptide construct comprises from about 25 amino acids to about 1200 amino acids, e.g., from about 25 amino acids to about 1100 amino acids, e.g., from about 25 amino acids to about 1000 amino acids, e.g., from about 25 amino acids to about 750 amino acids, e.g., from about 25 amino acids to about 500 amino acids. In some embodiments, the Plasmodium T cell string polypeptide construct comprises about 25, about 50, about 75, about 100, about 150, about 200, about 250, about 300, about 350, about 400, about 450, about 500, about 550, about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 950, about 1000, about 1050, about 1100, about 1150, or about 1200 amino acids. In some embodiments, the Plasmodium T cell string polypeptide construct further comprises one or more additional amino acid sequences, such as a secretory signal (e.g., a heterologous secretory signal), a transmembrane region (e.g., a heterologous transmembrane region), a trafficking signal, and / or a linker, as described herein.

[0241] AT cell antigen selection In some embodiments, the T cell antigen utilized in the Plasmodium T cell string polypeptide constructs described herein is HLA-I or HLA-II binding (e.g., to the HLA allele(s) present in the relevant population), HLA ligandomics data confirmed by mass spectrometry, Relatively high expression, Sequence preservation, manifestation in the early hepatic stage of the parasite life cycle, localization to the parasite vacuole membrane, Seroreactivity, immunogenicity (e.g., the presence of one or more B cell and / or T cell epitopes, e.g., evidence of the ability to induce sterile protection in model systems including humans, non-human primates, and / or mice); and and there is no sequence of 8 or more amino acids that overlaps with the human proteome, except where 6 or more amino acids are linker sequences.

[0242] In some embodiments, such properties are evaluated experimentally or computationally, hi some embodiments, such properties are evaluated by consultation with published reports.

[0243] For example, in some embodiments, HLA-I and / or HLA-II binding is experimentally assessed, and in some embodiments, predicted. In some embodiments, predicted HLA-I or HLA-II binding is assessed using algorithms such as neonmhc1 and / or neonmhc2, which predict and / or characterize MHC class I and MHC class II binding potential, respectively. Alternatively or additionally, in some embodiments, the MHC-peptide presentation prediction algorithm or MHC-peptide presentation predictor is or includes NetMHCpan or NetMHCIIpan. In some embodiments, a hidden Markov model approach may be utilized for MHC-peptide presentation prediction and / or characterization. In some embodiments, the peptide prediction model MARIA may be utilized. In some embodiments, NetMHCpan is not utilized to predict or characterize MHC binding potential for peptides as described herein. In some embodiments, the peptide prediction model MARIA may be utilized. In some embodiments, NetMHCIIpan is not utilized to predict or characterize MHC binding potential for peptides as described herein. In some embodiments, neither NetMHCpan nor NetMHCIIpan is utilized to predict or characterize MHC binding potential for the peptides described herein. In some embodiments, the MHC-peptide presentation prediction algorithm or predictor is or includes RECON® (Real-time Epitope Computation for ONcology), which provides high-quality MHC-peptide presentation predictions based on expression, processing, and binding capacity. See, e.g., Abelin et al., Immunity 21:315, 2017; Abelin et al., Immunity 15:766, 2019, each of which is incorporated by reference in its entirety.

[0244] In some embodiments, HLA binding and / or ligandomics assessment may take into account the geographic region of the subject to be immunized. For example, in some embodiments, the diversity of HLA alleles may be taken into account. In some embodiments, the T cell antigens include peptides (e.g., epitopes) that, when considered together, are predicted or determined to bind to a significant percentage (e.g., at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more) of the HLA alleles predicted or known to be present in the relevant region or population. In some embodiments, the T cell antigens include peptides that, when considered together, are predicted or determined to bind to the most common (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 most common, or at least 1, 2, 3, 4, or 5 of the 10 most common) HLA alleles predicted or known to be present in the relevant region or population.

[0245] In some embodiments, the expression level is experimentally determined (e.g., in a model system or in infected humans). In some embodiments, the expression level is a reported level (e.g., in a published or presented report). In some embodiments, the expression level is assessed as RNA (e.g., via RNASeq). In some embodiments (and typically preferably), the expression level is assessed as protein.

[0246] In some embodiments, sequence conservation is assessed, for example, using publicly available sequence evaluation software (e.g., multiple sequence alignment programs MAFFT, Clustal Omega, etc.). In some embodiments, sequence conservation is determined by consultation with publicly available resources (e.g., sequences). In some embodiments, sequence conservation includes consideration of currently or recently detected strains (e.g., in active outbreaks).

[0247] In some embodiments, surface exposure is assessed by reference to publicly available databases and / or software. In some embodiments, surface exposure is assessed by reference to publicly available data, such as those described in Swearingen et al., "Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics," PLoS Pathog (2016), the contents of which are incorporated herein by reference for purposes described herein.

[0248] In some embodiments, seroreactivity is assessed by contacting a serum sample from an infected individual with a polypeptide comprising a sequence of interest (which may be displayed, e.g., via phage display or peptide array, see, e.g., Whittemore et al. PlosOne, 2016, which is incorporated herein by reference in its entirety). In some embodiments, seroreactivity is assessed by consultation with literature reports and / or database data indicating serum recognition sequences.

[0249] In some embodiments, assessment of the presence of immunoreactivity and / or epitopes may be or include consultation with the Immune Epitope Database (IEDB), which those skilled in the art will recognize as a freely available resource funded by NIAID that catalogs experimental data on antibody and T-cell epitopes (see iedb.org).

[0250] In some embodiments, the ability to induce sterile protection is measured using the method described, for example, in Schofield et al. "γ Interferon, CD8 +T cells and antibodies required for immunity to malaria sporozoites”Nature 330,664-666 (1987), Weiss et al. (1988). al. “Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria.” Nature 341, 323-326 (1989), Rodrigues et al. (1991) “CD8+cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria.”Int.Immunol.3,579-585, Chakravarty et al. "CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes." Nat Med. 2007 Sep;13(9):1035-41. Epub 2007 Aug 19. (each of which is incorporated herein by reference in its entirety).

[0251] In some embodiments, the T cell antigen is characterized by dendritic cell presentation, which may exhibit HLA binding and / or immunogenicity. Without intending to be bound by any particular theory, it is proposed that dendritic cell presentation, for example, in peripheral lymph nodes, may induce CD8+ T cells that can migrate to the liver and eliminate, for example, parasite-infected liver cells. See, e.g., Chakravarty et al., "CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes." Nat Med. 2007 Sep;13(9):1035-41. Epub 2007 Aug 19, the entire contents of which are incorporated herein by reference for purposes set forth herein.

[0252] B. Exemplary T Cell Antigens In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more Plasmodium T cell antigens from a Plasmodium protein selected from CSP, LSA-1(a), LSA-1(b), TRAP, LSAP2, UIS3, IS4, LISP-1, LISP-2, LSA-3, EXP1, and LSAP1.

[0253] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise between 2 and about 20 Plasmodium T cell antigens (e.g., between about 2 and about 15, between about 2 and about 10, between about 2 and about 9, between about 2 and about 8, between about 2 and about 7, between about 2 and about 6, or between about 2 and about 5 Plasmodium T cell antigens). In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise between about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise four Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise five Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise six Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise seven Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise eight Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise nine Plasmodium T cell antigens. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise ten Plasmodium T cell antigens. In some embodiments, the malaria T cell peptide string constructs described herein comprise only an immunogenic portion of one or more of the included Plasmodium T cell antigens.

[0254] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP, e.g., a P. falciparum CSP, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium CSP polypeptide fragment. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, antigenic Plasmodium CSP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, antigenic Plasmodium CSP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, antigenic Plasmodium CSP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0255] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide, e.g., a Plasmodium LSA-1(a) polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(a) polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 149, 150, 151, 152, or 153. In some embodiments, the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 149, 150, 151, 152, or 153.

[0256] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide, e.g., a Plasmodium LSA-1(b) polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(b) polypeptide fragment. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 155. In some embodiments, antigenic Plasmodium LSA-1(b) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169. In some embodiments, antigenic Plasmodium LSA-1(b) polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.

[0257] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0258] In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an LSAP1 polypeptide, e.g., a Plasmodium LSAP1 polypeptide. In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an LSAP1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 302. In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an LSAP1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 302. In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP1 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 192. In some embodiments, antigenic Plasmodium LSAP1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 192.

[0259] In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide. In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210. In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0260] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0261] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, e.g., a Plasmodium ETRAMP10.3 polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227. In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0262] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide, e.g., a Plasmodium LISP-1 polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-1 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 234, 235, or 236. In some embodiments, the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of the amino acid sequence of SEQ ID NO: 234, 235, or 236.

[0263] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide, e.g., a Plasmodium LISP-2 polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-2 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 243, 244, 245, 246, or 247. In some embodiments, the antigenic Plasmodium LISP-2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 243, 244, 245, 246, or 247.

[0264] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-3 polypeptide, e.g., a Plasmodium LSA-3 polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 299. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 299. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-3 polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 249. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 249. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 254, 255, 256, 257, 258, 259, 260, 261, or 262. In some embodiments, the antigenic Plasmodium LSA-3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 254, 255, 256, 257, 258, 259, 260, 261, or 262.

[0265] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an EXP1 polypeptide, e.g., a Plasmodium EXP1 polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an EXP1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 314. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an EXP1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 314. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium EXP1 polypeptide fragment. In some embodiments, the antigenic Plasmodium EXP1 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 263. In some embodiments, the antigenic Plasmodium EXP1 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 263.

[0266] C. Transport Signals In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a trafficking signal. For example, in some embodiments, the trafficking signal is an MHC class I trafficking signal (MITD). In some embodiments, the MITD comprises or consists of the amino acid sequence according to SEQ ID NO: 479.

[0267] D. Secretion signal In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise a secretion signal that is functional, for example, in mammalian cells. In some embodiments, the secretion signal comprises or consists of a Plasmodium secretion signal. In some embodiments, the Plasmodium secretion signal comprises or consists of a Plasmodium CSP secretion signal.

[0268] In some embodiments, the secretory signal utilized is a heterologous secretory signal. In some embodiments, the heterologous secretory signal comprises or consists of a non-human secretory signal. In some embodiments, the heterologous secretory signal comprises or consists of a viral secretory signal. In some embodiments, the viral secretory signal comprises or consists of an HSV secretory signal (e.g., an HSV-1 or HSV-2 secretory signal). In some embodiments, the HSV secretory signal comprises or consists of an HSV glycoprotein D (gD) secretory signal. In some embodiments, the secretory signal comprises or consists of an Ebola virus secretory signal. In some embodiments, the Ebola virus secretory signal comprises or consists of an Ebola virus spike glycoprotein (SGP) secretory signal.

[0269] In some embodiments, the secretory signal is characterized by a length of about 15 to 30 amino acids.

[0270] In many embodiments, the secretion signal is located at the N-terminus of the Plasmodium T-cell string polypeptide construct described herein. In some embodiments, the secretion signal preferably allows the transport of the associated Plasmodium T-cell string polypeptide construct to a defined cellular compartment, preferably the cell surface, the endoplasmic reticulum (ER), or the endosomal-lysosomal compartment.

[0271] In some embodiments, the secretory signal is selected from the S1S2 secretory signal (aa 1-19), the immunoglobulin secretory signal (aa 1-22), the human SPARC secretory signal, the human insulin isoform 1 secretory signal, the human albumin secretory signal, etc. Those of skill in the art will recognize other secretory signals (e.g., SEQ ID NOS: 1-1115 and 1728, or fragment variants thereof), such as those disclosed in WO2017 / 081082, which is incorporated herein by reference in its entirety. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein do not comprise a secretory signal.

[0272] In some embodiments, the secretory signal is one listed in Table 3 or a secretory signal that differs by 1, 2, 3, 4, or 5 amino acids therefrom. In some embodiments, the signal sequence is selected from those included in Table 3 below and / or encoded by the sequences in Table 4 below. [Table 3] [Table 4]

[0273] E. Transmembrane region In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein comprise a transmembrane region. In some embodiments, the transmembrane region comprises or consists of a Plasmodium transmembrane region. In some embodiments, the transmembrane region utilized is one that is normally associated with CSP in nature. In some embodiments, the Plasmodium transmembrane region comprises or consists of a Plasmodium CSP glycosylphosphatidylinositol (GPI) anchor region, e.g., amino acids 374-397 of SEQ ID NO: 1. In some embodiments, the transmembrane region utilized is a heterologous transmembrane region.

[0274] In some embodiments, the transmembrane region is located at the N-terminus of the Plasmodium T-cell string polypeptide construct. In some embodiments, the transmembrane region is located at the C-terminus of the Plasmodium T-cell string polypeptide construct. In some embodiments, the transmembrane region is not located at the N-terminus or C-terminus of the Plasmodium T-cell string polypeptide construct.

[0275] Transmembrane regions are known in the art, any of which can be utilized in the Plasmodium T-cell string polypeptide constructs described herein. In some embodiments, the transmembrane region comprises or is a transmembrane domain of influenza virus hemagglutinin (HA), HIV-1 Env, equine infectious anemia virus (EIAV), murine leukemia virus (MLV), mouse mammary tumor virus, vesicular stomatitis virus (VSV) G protein, rabies virus, or a seven transmembrane domain receptor.

[0276] In some embodiments, the heterologous transmembrane region does not comprise a hemagglutinin transmembrane region. In some embodiments, the heterologous transmembrane region comprises or consists of a non-human transmembrane region. In some embodiments, the heterologous transmembrane region comprises or consists of a viral transmembrane region. In some embodiments, the heterologous transmembrane region comprises or consists of an HSV transmembrane region (e.g., an HSV-1 or HSV-2 transmembrane region). In some embodiments, the HSV transmembrane region comprises or consists of an HSV gD transmembrane region, e.g., comprises or consists of the amino acid sequence of SEQ ID NO: 447.

[0277] In some embodiments, the heterologous transmembrane region comprises or consists of a human transmembrane region. In some embodiments, the human transmembrane region comprises or consists of a human decay-accelerating factor glycosylphosphatidylinositol (hDAF-GPI) anchor region. In some embodiments, the hDAF-GPI anchor region comprises or consists of the amino acid sequence of SEQ ID NO: 450.

[0278] In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein do not include a transmembrane region.

[0279] F. Linker In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more linkers. In some embodiments, the linker is or comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, or more amino acids. In some embodiments, the linker is or comprises about 30 or fewer, 25 or fewer, 20 or fewer, 15 or fewer, 10 or fewer, or fewer amino acids. The linker can comprise any amino acid sequence and is not limited to specific amino acids. In some embodiments, the linker comprises one or more glycine (G) amino acids. In some embodiments, the linker comprises one or more serine (S) amino acids. In some embodiments, the linker comprises amino acids selected based on cleavage predictors to generate a highly cleavable linker.

[0280] In some embodiments, the linker is or comprises S-G4-S-G4-S. In some embodiments, the linker is or comprises an amino acid sequence according to SEQ ID NO: 455. In some embodiments, the linker is or comprises an amino acid sequence according to SEQ ID NO: 452. In some embodiments, the linker is according to any one of SEQ ID NOs: 453, 455, 452, 458 (GGS), 459 (GGGS), 456, 460, 454, or 457. In some embodiments, the linker is or comprises a sequence set forth in WO2017 / 081082, the entire contents of which are incorporated herein by reference (see SEQ ID NOs: 1509-1565, or fragments or variants thereof).

[0281] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a linker between two Plasmodium T cell antigens.

[0282] G. Embodiments of Plasmodium T-Cell String Polypeptide Constructs In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise two or more of: (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (iii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, (iv) an antigenic Plasmodium TRAP polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium UIS3 polypeptide fragment, (vii) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (viii) an antigenic Plasmodium LISP-1 polypeptide fragment, (ix) an antigenic Plasmodium LISP-2 polypeptide fragment, and (x) an antigenic Plasmodium LSA-3 polypeptide fragment.

[0283] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more Plasmodium polypeptides or portions thereof from Plasmodium falciparum. In some embodiments, the one or more Plasmodium polypeptides or portions thereof are one or more P. falciparum T cell antigens. In some embodiments, the one or more P. falciparum T cell antigens are from P. falciparum isolate 3D7.

[0284] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein do not include one or more Plasmodium polypeptides or portions thereof from Plasmodium berghei (e.g., antigenic Plasmodium berghei CSP polypeptide fragments).

[0285] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein do not comprise an antigenic fragment of a bacterial polypeptide. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein do not comprise an antigenic bacillus Calmette-Guerin (BCG) polypeptide fragment. In some embodiments, the antigenic BCG polypeptide fragment comprises an amino acid sequence according to SEQ ID NO: 461. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein do not comprise an antigenic tetanus toxin (TT) polypeptide fragment. In some embodiments, the antigenic TT polypeptide fragment comprises an amino acid sequence according to SEQ ID NO: 462.

[0286] In some embodiments, the Plasmodium T-cell string polypeptide constructs described herein do not comprise an antigenic Plasmodium sporozoite threonine-asparagine-rich protein (STARP) polypeptide fragment. In some embodiments, the antigenic Plasmodium STARP polypeptide fragment comprises an amino acid sequence according to SEQ ID NO: 463.

[0287] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more of the Plasmodium polypeptide regions or portions thereof (e.g., antigenic fragments) described above. Exemplary combinations are described below.

[0288] Constructs containing CSP, TRAP, LSA-1(a), LSA-1(b), LSA-3, and LSAP2 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide (or one or more antigenic Plasmodium CSP polypeptide fragments), a Plasmodium TRAP polypeptide (or one or more antigenic Plasmodium TRAP polypeptide fragments), a Plasmodium LSA-1(a) polypeptide (or one or more antigenic Plasmodium LSA-1(a) polypeptide fragments), a Plasmodium LSA-1(b) polypeptide (or one or more antigenic Plasmodium LSA-1(b) polypeptide fragments), a Plasmodium LSA-3 polypeptide (or one or more antigenic Plasmodium LSA-3 polypeptide fragments), and a Plasmodium LSAP2 polypeptide (or one or more antigenic Plasmodium LSAP2 polypeptide fragments), wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0289] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP polypeptide, e.g., a P. falciparum CSP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more antigenic Plasmodium CSP polypeptide fragments, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, the antigenic Plasmodium CSP polypeptide fragment does not contain the N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0290] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide, e.g., a P. falciparum TRAP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0291] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide, e.g., a Plasmodium LSA-1(a) polypeptide, e.g., a P. falciparum LSA-1(a) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(a) polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 149, 150, 151, 152, or 153.In some embodiments, the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 149, 150, 151, 152, or 153.

[0292] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide, e.g., a Plasmodium LSA-1(b) polypeptide, e.g., a P. falciparum LSA-1(b) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(b) polypeptide fragment. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.

[0293] In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an LSA-3 polypeptide, e.g., a Plasmodium LSA-3 polypeptide, e.g., a P. falciparum LSA-3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an LSA-3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 299. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an LSA-3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 299. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an antigenic Plasmodium LSA-3 polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 249. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 249. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 254, 255, 256, 257, 258, 259, 260, 261, or 262.In some embodiments, the antigenic Plasmodium LSA-3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 254, 255, 256, 257, 258, 259, 260, 261, or 262.

[0294] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide, e.g., a P. falciparum LSAP2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0295] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (iv) an antigenic Plasmodium LSA-1(b) polypeptide fragment, (v) an antigenic Plasmodium LSA-3 polypeptide fragment, and (vi) an antigenic Plasmodium LSAP2 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (iv) an antigenic Plasmodium LSA-1(b) polypeptide fragment, (v) an antigenic Plasmodium LSA-3 polypeptide fragment, and (vi) an antigenic Plasmodium LSAP2 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:3. In some embodiments, the Plasmodium T-cell string polypeptide construct described herein comprises the amino acid sequence of SEQ ID NO:3.In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (ii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, (iii) an antigenic Plasmodium LSAP2 polypeptide fragment, (iv) an antigenic Plasmodium CSP polypeptide fragment, (v) an antigenic Plasmodium LSA-3 polypeptide fragment, and (vi) an antigenic Plasmodium TRAP polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:6. In some embodiments, the Plasmodium T-cell string polypeptide construct described herein comprises the amino acid sequence of SEQ ID NO:6.

[0296] Constructs including LSAP1, EXP1, UIS3, ETRAMP10.3, LISP-1, and LISP-2 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a Plasmodium LSAP1 polypeptide (or one or more antigenic Plasmodium LSAP1 polypeptide fragments), a Plasmodium EXP1 polypeptide (or one or more antigenic Plasmodium EXP1 polypeptide fragments), a Plasmodium UIS3 polypeptide (or one or more antigenic Plasmodium UIS3 polypeptide fragments), a Plasmodium ETRAMP10.3 polypeptide (or one or more antigenic Plasmodium ETRAMP10.3 polypeptide fragments), a Plasmodium LISP-1 polypeptide (or one or more antigenic Plasmodium LISP-1 polypeptide fragments), and a Plasmodium LISP-2 polypeptide (or one or more antigenic Plasmodium LISP-2 polypeptide fragments), wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0297] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP1 polypeptide, e.g., a Plasmodium LSAP1 polypeptide, e.g., a P. falciparum LSAP1 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 302. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 302. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP1 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 192. In some embodiments, antigenic Plasmodium LSAP1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 192.

[0298] In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an EXP1 polypeptide, e.g., a Plasmodium EXP1 polypeptide, e.g., a P. falciparum EXP1 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an EXP1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 314. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an EXP1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 314. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an antigenic Plasmodium EXP1 polypeptide fragment. In some embodiments, the antigenic Plasmodium EXP1 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 263. In some embodiments, the antigenic Plasmodium EXP1 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 263.

[0299] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide, e.g., a P. falciparum UIS3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0300] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, such as a Plasmodium ETRAMP10.3 polypeptide, such as a P. falciparum ETRAMP10.3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227.In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0301] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide, e.g., a Plasmodium LISP-1 polypeptide, e.g., a P. falciparum LISP-1 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-1 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 234, 235, or 236. In some embodiments, the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 234, 235, or 236.

[0302] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide, e.g., a Plasmodium LISP-2 polypeptide, e.g., a P. falciparum LISP-2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-2 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 243, 244, 245, 246, or 247. In some embodiments, the antigenic Plasmodium LISP-2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 243, 244, 245, 246, or 247.

[0303] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise (i) an antigenic Plasmodium LSAP1 polypeptide fragment, (ii) an antigenic Plasmodium EXP1 polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LISP-1 polypeptide fragment, and (vi) an antigenic Plasmodium LISP-2 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium EXP1 polypeptide fragment, (ii) an antigenic Plasmodium UIS3 polypeptide fragment, (iii) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (iv) an antigenic Plasmodium LSAP1 polypeptide fragment, (v) an antigenic Plasmodium LISP-2 polypeptide fragment, and (vi) an antigenic Plasmodium LISP-1 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:9. In some embodiments, the Plasmodium T-cell string polypeptide construct described herein comprises the amino acid sequence of SEQ ID NO:9.In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium UIS3 polypeptide fragment, (ii) an antigenic Plasmodium LSAP1 polypeptide fragment, (iii) an antigenic Plasmodium LISP-1 polypeptide fragment, (iv) an antigenic Plasmodium EXP1 polypeptide fragment, (v) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and (vi) an antigenic Plasmodium LISP-2 polypeptide fragment. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 12. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise the amino acid sequence of SEQ ID NO: 12.

[0304] Constructs containing CSP, TRAP, LSAP2, UIS3, and ETRAMP10.3 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide (or one or more antigenic Plasmodium CSP polypeptide fragments), a Plasmodium TRAP polypeptide (or one or more antigenic Plasmodium TRAP polypeptide fragments), a Plasmodium LSAP2 polypeptide (or one or more antigenic Plasmodium LSAP2 polypeptide fragments), a Plasmodium UIS3 polypeptide (or one or more antigenic Plasmodium UIS3 polypeptide fragments), and a Plasmodium ETRAMP10.3 polypeptide (or one or more antigenic Plasmodium ETRAMP10.3 polypeptide fragments), wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0305] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP polypeptide, e.g., a P. falciparum CSP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more antigenic Plasmodium CSP polypeptide fragments, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, the antigenic Plasmodium CSP polypeptide fragment does not contain the N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0306] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide, e.g., a P. falciparum TRAP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0307] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide, e.g., a P. falciparum LSAP2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0308] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide, e.g., a P. falciparum UIS3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0309] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, such as a Plasmodium ETRAMP10.3 polypeptide, such as a P. falciparum ETRAMP10.3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227.In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0310] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and (v) an antigenic Plasmodium LSAP2 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and (v) an antigenic Plasmodium LSAP2 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 15. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise the amino acid sequence of SEQ ID NO: 15.

[0311] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and (v) an antigenic Plasmodium LSAP2 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 57. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise the amino acid sequence of SEQ ID NO: 57.

[0312] Constructs including CSP, TRAP, LSA-1(a), LSA-1(b), LSA-3, LSAP2, UIS3, and ETRAMP10.3 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein are selected from the group consisting of a CSP polypeptide (or one or more antigenic Plasmodium CSP polypeptide fragments), a Plasmodium TRAP polypeptide (or one or more antigenic Plasmodium TRAP polypeptide fragments), a Plasmodium LSA-1(a) polypeptide (or one or more antigenic Plasmodium LSA-1(a) polypeptide fragments), a Plasmodium LSA-1(b) polypeptide (or one or more antigenic Plasmodium LSA-1(b) polypeptide fragments), a Plasmodium LSA-3 polypeptide (or one or more antigenic Plasmodium LSA-3 polypeptide fragments), a Plasmodium LSAP2 polypeptide (or one or more antigenic Plasmodium LSAP2 polypeptide fragments), a Plasmodium UIS3 polypeptide (or one or more antigenic Plasmodium UIS3 polypeptide fragments), and a Plasmodium ETRAMP10.3 polypeptide (or one or more antigenic Plasmodium ETRAMP10.3 polypeptide fragment), and the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0313] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP polypeptide, e.g., a P. falciparum CSP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more antigenic Plasmodium CSP polypeptide fragments, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, the antigenic Plasmodium CSP polypeptide fragment does not contain the N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0314] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide, e.g., a P. falciparum TRAP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0315] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide, e.g., a Plasmodium LSA-1(a) polypeptide, e.g., a P. falciparum LSA-1(a) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(a) polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 149, 150, 151, 152, or 153.In some embodiments, the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 149, 150, 151, 152, or 153.

[0316] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide, e.g., a Plasmodium LSA-1(b) polypeptide, e.g., a P. falciparum LSA-1(b) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(b) polypeptide fragment. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.

[0317] In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an LSA-3 polypeptide, e.g., a Plasmodium LSA-3 polypeptide, e.g., a P. falciparum LSA-3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an LSA-3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 299. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an LSA-3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 299. In some embodiments, a Plasmodium T cell string polypeptide construct described herein comprises an antigenic Plasmodium LSA-3 polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 249. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 249. In some embodiments, antigenic Plasmodium LSA-3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 254, 255, 256, 257, 258, 259, 260, 261, or 262.In some embodiments, the antigenic Plasmodium LSA-3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 254, 255, 256, 257, 258, 259, 260, 261, or 262.

[0318] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide, e.g., a P. falciparum LSAP2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0319] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide, e.g., a P. falciparum UIS3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0320] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, such as a Plasmodium ETRAMP10.3 polypeptide, such as a P. falciparum ETRAMP10.3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227.In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0321] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium LSA-3 polypeptide fragment, (vii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, and (viii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium LSA-3 polypeptide fragment, (vii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, and (viii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 18.In some embodiments, the Plasmodium T-cell string polypeptide construct described herein comprises the amino acid sequence of SEQ ID NO:18.

[0322] Constructs including CSP, TRAP, LSA-1(a), LSA-1(b), LSAP2, UIS3, ETRAMP10.3, LISP-1, and LISP-2 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein are selected from the group consisting of a CSP polypeptide (or one or more antigenic Plasmodium CSP polypeptide fragments), a Plasmodium TRAP polypeptide (or one or more antigenic Plasmodium TRAP polypeptide fragments), a Plasmodium LSA-1(a) polypeptide (or one or more antigenic Plasmodium LSA-1(a) polypeptide fragments), a Plasmodium LSA-1(b) polypeptide (or one or more antigenic Plasmodium LSA-1(b) polypeptide fragments), a Plasmodium LSAP2 polypeptide (or one or more antigenic Plasmodium LSAP2 polypeptide fragments), a Plasmodium UIS3 polypeptide (or one or more antigenic Plasmodium UIS3 polypeptide fragments), a Plasmodium ETRAMP10.3 polypeptide (or one or more antigenic Plasmodium ETRAMP10.3 polypeptide fragments), a Plasmodium LISP-1 polypeptide (or one or more antigenic Plasmodium LISP-1 polypeptide fragments), and a Plasmodium LISP-2 polypeptide (or one or more antigenic Plasmodium LISP-2 polypeptide fragments), wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0323] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP polypeptide, e.g., a P. falciparum CSP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more antigenic Plasmodium CSP polypeptide fragments, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, the antigenic Plasmodium CSP polypeptide fragment does not contain the N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0324] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide, e.g., a P. falciparum TRAP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0325] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide, e.g., a Plasmodium LSA-1(a) polypeptide, e.g., a P. falciparum LSA-1(a) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(a) polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 149, 150, 151, 152, or 153.In some embodiments, the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 149, 150, 151, 152, or 153.

[0326] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide, e.g., a Plasmodium LSA-1(b) polypeptide, e.g., a P. falciparum LSA-1(b) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(b) polypeptide fragment. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.

[0327] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide, e.g., a P. falciparum LSAP2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0328] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide, e.g., a P. falciparum UIS3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0329] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, such as a Plasmodium ETRAMP10.3 polypeptide, such as a P. falciparum ETRAMP10.3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227.In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0330] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide, e.g., a Plasmodium LISP-1 polypeptide, e.g., a P. falciparum LISP-1 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-1 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 234, 235, or 236. In some embodiments, the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 234, 235, or 236.

[0331] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide, e.g., a Plasmodium LISP-2 polypeptide, e.g., a P. falciparum LISP-2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-2 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 243, 244, 245, 246, or 247. In some embodiments, the antigenic Plasmodium LISP-2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 243, 244, 245, 246, or 246.

[0332] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, (viii) an antigenic Plasmodium LISP-2 polypeptide fragment, and (ix) an antigenic Plasmodium LISP-1 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, (viii) an antigenic Plasmodium LISP-2 polypeptide fragment, and (ix) an antigenic Plasmodium LISP-1 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 24. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise the amino acid sequence of SEQ ID NO: 24.

[0333] Constructs containing CSP, TRAP, LSA-1(a), LSA-1(b), LSAP2, UIS3, ETRAMP10.3, and LISP-1 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein are selected from the group consisting of a CSP polypeptide (or one or more antigenic Plasmodium CSP polypeptide fragments), a Plasmodium TRAP polypeptide (or one or more antigenic Plasmodium TRAP polypeptide fragments), a Plasmodium LSA-1(a) polypeptide (or one or more antigenic Plasmodium LSA-1(a) polypeptide fragments), a Plasmodium LSA-1(b) polypeptide (or one or more antigenic Plasmodium LSA-1(b) polypeptide fragments), a Plasmodium LSAP2 polypeptide (or one or more antigenic Plasmodium LSAP2 polypeptide fragments), a Plasmodium UIS3 polypeptide (or one or more antigenic Plasmodium UIS3 polypeptide fragments), a Plasmodium ETRAMP10.3 polypeptide (or one or more antigenic Plasmodium ETRAMP10.3 polypeptide fragments), and a Plasmodium LISP-1 polypeptide (or one or more antigenic Plasmodium LISP-1 polypeptide fragment), and the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0334] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP polypeptide, e.g., a P. falciparum CSP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more antigenic Plasmodium CSP polypeptide fragments, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, the antigenic Plasmodium CSP polypeptide fragment does not contain the N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0335] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide, e.g., a P. falciparum TRAP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0336] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide, e.g., a Plasmodium LSA-1(a) polypeptide, e.g., a P. falciparum LSA-1(a) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(a) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 293. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(a) polypeptide fragment. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 144. In some embodiments, antigenic Plasmodium LSA-1(a) polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 149, 150, 151, 152, or 153.In some embodiments, the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 149, 150, 151, 152, or 153.

[0337] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide, e.g., a Plasmodium LSA-1(b) polypeptide, e.g., a P. falciparum LSA-1(b) polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSA-1(b) polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 296. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSA-1(b) polypeptide fragment. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 155. In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.In some embodiments, the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 160, 161, 162, 163, 164, 165, 166, 167, 168, or 169.

[0338] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide, e.g., a P. falciparum LSAP2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0339] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide, e.g., a P. falciparum UIS3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0340] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, such as a Plasmodium ETRAMP10.3 polypeptide, such as a P. falciparum ETRAMP10.3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227.In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0341] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide, e.g., a Plasmodium LISP-1 polypeptide, e.g., a P. falciparum LISP-1 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-1 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 234, 235, or 236. In some embodiments, the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 234, 235, or 236.

[0342] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, and (viii) an antigenic Plasmodium LISP-1 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise, in order, (i) an antigenic Plasmodium CSP polypeptide fragment, (ii) an antigenic Plasmodium TRAP polypeptide fragment, (iii) an antigenic Plasmodium UIS3 polypeptide fragment, (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, (v) an antigenic Plasmodium LSAP2 polypeptide fragment, (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment, (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, and (viii) an antigenic Plasmodium LISP-1 polypeptide fragment, wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:27.In some embodiments, the Plasmodium T-cell string polypeptide construct described herein comprises the amino acid sequence of SEQ ID NO:27.

[0343] Constructs including CSP, TRAP, LSAP2, UIS3, ETRAMP10.3, LISP-1, and LISP-2 In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide (or one or more antigenic Plasmodium CSP polypeptide fragments), a Plasmodium TRAP polypeptide (or one or more antigenic Plasmodium TRAP polypeptide fragments), a Plasmodium LSAP2 polypeptide (or one or more antigenic Plasmodium LSAP2 polypeptide fragments), a Plasmodium UIS3 polypeptide (or one or more antigenic Plasmodium UIS3 polypeptide fragments), a Plasmodium ETRAMP10.3 polypeptide (or one or more antigenic Plasmodium ETRAMP10.3 polypeptide fragments), a Plasmodium LISP-1 polypeptide (or one or more antigenic Plasmodium LISP-1 polypeptide fragments), and a Plasmodium LISP-2 polypeptide (or one or more antigenic Plasmodium LISP-2 polypeptide fragments), wherein the Plasmodium is preferably Plasmodium falciparum, more preferably Plasmodium falciparum isolate 3D7.

[0344] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide, e.g., a Plasmodium CSP polypeptide, e.g., a P. falciparum CSP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a CSP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 1. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise one or more antigenic Plasmodium CSP polypeptide fragments, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal end region and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises the Plasmodium CSP N-terminal domain and a junction region. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment containing at least a portion of the N-terminal domain does not contain the C-terminal region.In some embodiments, the antigenic Plasmodium CSP polypeptide fragment does not contain the N-terminal domain. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 133. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 138, 139, 140, 141, or 142. In some embodiments, the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:138, 139, 140, 141, or 142.

[0345] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide, e.g., a Plasmodium TRAP polypeptide, e.g., a P. falciparum TRAP polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a TRAP polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 287. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium TRAP polypeptide fragment. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 171. In some embodiments, antigenic Plasmodium TRAP polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 171. In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.In some embodiments, the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, or 190.

[0346] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide, e.g., a Plasmodium LSAP2 polypeptide, e.g., a P. falciparum LSAP2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an LSAP2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 305. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LSAP2 polypeptide fragment. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 198. In some embodiments, antigenic Plasmodium LSAP2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.In some embodiments, the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 203, 204, 205, 206, 207, 208, 209, or 210.

[0347] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide, e.g., a Plasmodium UIS3 polypeptide, e.g., a P. falciparum UIS3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a UIS3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 359. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium UIS3 polypeptide fragment. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:212. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO:217. In some embodiments, antigenic Plasmodium UIS3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO:217.

[0348] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide, such as a Plasmodium ETRAMP10.3 polypeptide, such as a P. falciparum ETRAMP10.3 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an ETRAMP10.3 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 362. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium ETRAMP10.3 polypeptide fragment. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 219. In some embodiments, antigenic Plasmodium ETRAMP10.3 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 224, 225, 226, or 227.In some embodiments, the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO:224, 225, 226, or 227.

[0349] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide, e.g., a Plasmodium LISP-1 polypeptide, e.g., a P. falciparum LISP-1 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-1 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 308. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-1 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 229. In some embodiments, antigenic Plasmodium LISP-1 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 234, 235, or 236. In some embodiments, the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 234, 235, or 236.

[0350] In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide, e.g., a Plasmodium LISP-2 polypeptide, e.g., a P. falciparum LISP-2 polypeptide, preferably from Plasmodium falciparum isolate 3D7. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise a LISP-2 polypeptide comprising or consisting of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 311. In some embodiments, the Plasmodium T cell string polypeptide constructs described herein comprise an antigenic Plasmodium LISP-2 polypeptide fragment. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence according to SEQ ID NO: 238. In some embodiments, antigenic Plasmodium LISP-2 polypeptide fragments comprise or consist of an amino acid sequence having at least 85% (e.g., at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity to SEQ ID NO: 243, 244, 245, 246, or 247. In some embodiments, the antigenic Plasmodium LISP-2 polypeptide fragment comprises or consists of an amino acid sequence according to SEQ ID NO: 243, 244, 245, 246, or 247.

[0351] In some embodiments, the Plas...

Claims

1. A polyribonucleotide encoding a polypeptide, said polypeptide comprising one or more Plasmodium T cell antigens, said one or more Plasmodium T cell antigens comprising: (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (iii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (iv) an antigenic Plasmodium TRAP polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium UIS3 polypeptide fragment; (vii) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (viii) an antigenic Plasmodium LISP-1 polypeptide fragment; (ix) an antigenic Plasmodium LISP-2 polypeptide fragment, and (x) an antigenic Plasmodium LSA-3 polypeptide fragment.

2. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and 2. The polyribonucleotide of claim 1, comprising or consisting of: (v) an antigenic Plasmodium LSAP2 polypeptide fragment.

3. 3. The polyribonucleotide of claim 1, wherein the polypeptide comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:

15.

4. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-3 polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(a) polypeptide fragment, and (viii) an antigenic Plasmodium LSA-1(b) polypeptide fragment.

5. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (viii) an antigenic Plasmodium LISP-2 polypeptide fragment, and (ix) an antigenic Plasmodium LISP-1 polypeptide fragment.

6. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment, and (viii) an antigenic Plasmodium LISP-1 polypeptide fragment.

7. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LISP-2 polypeptide fragment, and (vii) an antigenic Plasmodium LISP-1 polypeptide fragment.

8. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(b) polypeptide fragment, and (vii) an antigenic Plasmodium LISP-1 polypeptide fragment.

9. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium CSP polypeptide fragment; (ii) an antigenic Plasmodium TRAP polypeptide fragment; (iii) an antigenic Plasmodium UIS3 polypeptide fragment; (iv) an antigenic Plasmodium ETRAMP10.3 polypeptide fragment; (v) an antigenic Plasmodium LSAP2 polypeptide fragment; (vi) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (vii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (viii) an antigenic Plasmodium LISP-2 polypeptide fragment; (ix) an antigenic Plasmodium LISP-1 polypeptide fragment, and 3. The polyribonucleotide of claim 1, comprising or consisting of (x) an antigenic Plasmodium LSA-3 polypeptide fragment.

10. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (ii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (iii) an antigenic Plasmodium LISP-2 polypeptide fragment; (iv) an antigenic Plasmodium LISP-1 polypeptide fragment, and (v) an antigenic Plasmodium LSA-3 polypeptide fragment.

11. the one or more Plasmodium T cell antigens are (i) an antigenic Plasmodium LSA-1(a) polypeptide fragment; (ii) an antigenic Plasmodium LSA-1(b) polypeptide fragment; (iii) an antigenic Plasmodium LISP-2 polypeptide fragment, and (iv) an antigenic Plasmodium LISP-1 polypeptide fragment.

12. 12. The polyribonucleotide of claim 11, wherein the polypeptide comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:

45.

13. 10. The polyribonucleotide of claim 1, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium CSP polypeptide fragment, and the antigenic Plasmodium CSP polypeptide fragment comprises a Plasmodium CSP N-terminal region.

14. 14. The polyribonucleotide of claim 13, wherein the antigenic Plasmodium CSP polypeptide fragment further comprises a Plasmodium CSP N-terminal end region.

15. 15. The polyribonucleotide of claim 13 or 14, wherein the antigenic Plasmodium CSP polypeptide fragment further comprises a Plasmodium CSP junction region.

16. 16. The polyribonucleotide of any one of claims 13 to 15, wherein the antigenic Plasmodium CSP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

133.

17. 10. The polyribonucleotide of claim 1, wherein the one or more Plasmodium T cell antigens do not comprise an antigenic Plasmodium berghei CSP polypeptide fragment.

18. 18. The polyribonucleotide of any one of claims 1, 4-6, and 9-17, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium LSA-1(a) polypeptide fragment, and the antigenic Plasmodium LSA-1(a) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

144.

19. 19. The polyribonucleotide of any one of claims 1, 4-6, and 8-18, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium LSA-1(b) polypeptide fragment, and the antigenic Plasmodium LSA-1(b) polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

155.

20. 20. The polyribonucleotide of any one of claims 1 to 9 and 13 to 19, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium TRAP polypeptide fragment, and the antigenic Plasmodium TRAP polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

171.

21. 21. The polyribonucleotide of any one of claims 1 to 9 and 13 to 20, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium LSAP2 polypeptide fragment, and the antigenic Plasmodium LSAP2 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

198.

22. 22. The polyribonucleotide of any one of claims 1 to 9 and 13 to 21, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium UIS3 polypeptide fragment, and the antigenic Plasmodium UIS3 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

212.

23. 23. The polyribonucleotide of any one of claims 1 to 9 and 13 to 22, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium ETRAMP10.3 polypeptide fragment, and the antigenic Plasmodium ETRAMP10.3 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to the amino acid sequence according to SEQ ID NO:

219.

24. 24. The polyribonucleotide of any one of claims 1 and 5 to 23, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium LISP-1 polypeptide fragment, and the antigenic Plasmodium LISP-1 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

229.

25. 25. The polyribonucleotide of any one of claims 1, 5, 7, and 9-24, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium LISP-2 polypeptide fragment, and the antigenic Plasmodium LISP-2 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

238.

26. 26. The polyribonucleotide of any one of claims 1, 4, 9, 10, and 13-25, wherein the one or more Plasmodium T cell antigens comprise the antigenic Plasmodium LSA-3 polypeptide fragment, and the antigenic Plasmodium LSA-3 polypeptide fragment comprises or consists of an amino acid sequence having at least 85% sequence identity to an amino acid sequence according to SEQ ID NO:

249.

27. The polyribonucleotide of any one of claims 1 to 26, wherein the polypeptide does not comprise an antigenic fragment of a bacterial polypeptide.

28. 28. The polyribonucleotide of any one of claims 1 to 27, wherein the one or more Plasmodium T cell antigens do not comprise an antigenic Plasmodium sporozoite threonine-asparagine-rich protein (STARP) polypeptide fragment, and optionally, the antigenic Plasmodium STARP polypeptide fragment comprises an amino acid sequence according to SEQ ID NO:

463.

29. The polyribonucleotide of any one of claims 1 to 28, further comprising a sequence encoding an MHC class I transport signal (MITD).

30. The polyribonucleotide of any one of claims 1 to 29, wherein the polypeptide comprises a secretion signal.

31. 31. The polyribonucleotide of claim 30, wherein the secretion signal comprises or consists of a Plasmodium secretion signal, preferably a Plasmodium CSP secretion signal.

32. 31. The polyribonucleotide of claim 30, wherein the secretion signal comprises or consists of a heterologous secretion signal.

33. 33. The polyribonucleotide of claim 32, wherein the heterologous secretory signal comprises or consists of a non-human secretory signal.

34. The heterologous secretory signal comprises or consists of a viral secretory signal, preferably the viral secretory signal is (a) an HSV-1 or HSV-2 secretory signal, even more preferably wherein said viral secretory signal comprises or consists of the HSV glycoprotein D (gD) secretory signal, or 33. The polyribonucleotide of claim 32, comprising or consisting of (b) an Ebola virus secretory signal, even more preferably wherein said viral secretory signal comprises or consists of an Ebola virus spike glycoprotein (SGP) secretory signal.

35. The polyribonucleotide of any one of claims 1 to 34, wherein the polypeptide comprises a transmembrane region.

36. 36. The polyribonucleotide of claim 35, wherein the transmembrane region comprises or consists of a Plasmodium transmembrane region, preferably wherein the Plasmodium transmembrane region comprises or consists of a Plasmodium CSP glycosylphosphatidylinositol (GPI) anchor region.

37. The transmembrane region comprises or consists of a heterologous transmembrane region, preferably the heterologous transmembrane region comprises: (a) does not contain a hemagglutin transmembrane domain; (b) comprising or consisting of a viral transmembrane domain, preferably wherein said viral transmembrane domain comprises or consists of an HSV-1 or HSV-2 transmembrane domain, and even more preferably wherein said HSV transmembrane domain comprises or consists of an HSV gD transmembrane domain, or (c) a human transmembrane domain comprising or consisting of a human decay-accelerating factor glycosylphosphatidylinositol (hDAF-GPI) anchor domain;

38. The polyribonucleotide of any one of claims 1 to 29 and 35 to 37, wherein the polypeptide does not contain a secretory signal.

39. The polyribonucleotide of any one of claims 1 to 34, wherein the polypeptide does not include a transmembrane region.

40. 40. The polyribonucleotide of any one of claims 1 to 39, wherein the one or more Plasmodium T cell antigens are one or more P. falciparum T cell antigens, preferably the one or more P. falciparum T cell antigens are from P. falciparum isolate 3D7.

41. The polyribonucleotide according to any one of claims 1 to 40, wherein the polyribonucleotide is an isolated polyribonucleotide.

42. 42. The polyribonucleotide of any one of claims 1 to 41, wherein the polyribonucleotide is an engineered polyribonucleotide.

43. The polyribonucleotide according to any one of claims 1 to 42, wherein the polyribonucleotide is a codon-optimized polyribonucleotide.

44. In the order 5' to 3', (i) a 5'UTR comprising or consisting of a modified human alpha-globin 5'-UTR; (ii) a polyribonucleotide according to any one of claims 1 to 43; (iii) a 3′UTR comprising or consisting of a first sequence from a split amino-terminal enhancer (AES) messenger RNA and a second sequence from a mitochondrially encoded 12S ribosomal RNA; and (iv) an RNA construct comprising a polyA tail sequence.

45. 45. The RNA construct of claim 44, further comprising a 5' cap.

46. A composition comprising one or more polyribonucleotides according to any one of claims 1 to 43, or an RNA construct according to claim 44 or 45.

47. further comprising a lipid nanoparticle, polyplex (PLX), lipidated polyplex (LPLX), or liposome; 47. The composition of claim 46, wherein the one or more polyribonucleotides are fully or partially encapsulated within the lipid nanoparticle, the polyplex (PLX), the lipidated polyplex (LPLX), or the liposome.

48. 48. A pharmaceutical composition comprising the composition of claim 46 or 47 and at least one pharmaceutically acceptable excipient.

49. It is a combination, (i) a first pharmaceutical composition comprising a first polyribonucleotide, wherein the first polyribonucleotide encodes a first polypeptide, and the first polypeptide comprises one or more Plasmodium T cell antigens; and (ii) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide encodes a second polypeptide, and the second polypeptide comprises one or more Plasmodium antigenic polypeptide regions or portions thereof.

50. 50. The combination according to claim 49, wherein the first polyribonucleotide is a polyribonucleotide according to any one of claims 1 to 43.

51. 51. The combination of claim 49 or 50, wherein the one or more Plasmodium antigenic polypeptide regions or portions thereof of the second polypeptide comprise one or more Plasmodium CSP regions or portions thereof.

52. It is a combination, (i) a first pharmaceutical composition comprising a polyribonucleotide encoding a first polypeptide, wherein the first polypeptide comprises one or more Plasmodium T cell antigens, and the one or more Plasmodium T cell antigens comprise a Plasmodium N-terminal region or portion thereof, but do not comprise a Plasmodium C-terminal region or portion thereof; (ii) a second pharmaceutical composition comprising a polyribonucleotide encoding a second polypeptide, wherein the second polypeptide comprises one or more Plasmodium CSP polypeptide regions or portions thereof, and the one or more Plasmodium CSP polypeptide regions or portions thereof include a Plasmodium CSP C-terminal region or portion thereof, but do not include a Plasmodium CSP N-terminal region or portion thereof.

53. It is a combination, (i) a first pharmaceutical composition comprising a first polyribonucleotide, wherein the first polyribonucleotide is the polyribonucleotide of claim 2 or 3; and (ii) a second pharmaceutical composition comprising a second polyribonucleotide, wherein the second polyribonucleotide is the polyribonucleotide of claim 11 or 12.

54. A method for treating or preventing a malarial infection, comprising administering to a subject a polyribonucleotide according to any one of claims 1 to 43, an RNA construct according to claim 44 or 45, a composition according to claim 46 or 47, a pharmaceutical composition according to claim 48, or a combination according to any one of claims 49 to 53.

55. 49. The pharmaceutical composition of claim 48 for use in the treatment or prevention of a malaria infection comprising administering one or more doses of the pharmaceutical composition to a subject.

56. 54. A combination according to any one of claims 49 to 53 for use in the treatment or prevention of a malarial infection comprising administering one or more doses of said combination to a subject.

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