Self-assembled viral spike-EABR nanoparticles

Abstract

The present application discloses methods, compositions, and kits suitable for use in vaccination. In some embodiments, a nucleic acid composition (e.g., mRNA vaccine, DNA vaccine) is provided that includes a polynucleotide encoding a fusion protein. The fusion protein may include an antigenic polypeptide (AP) and an endosomal sorting complex for transport (ESCRT)-recruitment domain (ERD). A plurality of fusion proteins can self-assemble into enveloped nanoparticles that are secreted from cells expressing the fusion proteins. In some embodiments, a population of ENPs is provided.

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims the benefit under 35 USC §119(e) of U.S. Provisional Patent Application No. 63 / 208,889, filed June 9, 2021, the contents of which are incorporated by reference in their entirety into this application for all purposes.

[0002] [Reference to sequence listing] This application is filed together with an electronic sequence listing, which is provided as a file entitled 30KJ_302443_WO_Sequence_Listing, created on June 5, 2022, and is 28 kilobytes in size. The information in the electronic sequence listing is incorporated by reference in its entirety into this application.

[0003] [Field] The present invention relates broadly to the field of immunomedicine and, in particular, to self-assembling nanoparticles as vaccine platforms. [Background technology]

[0004] [Description of related technology] The ongoing COVID-19 pandemic, which has infected over 500 million people and killed 6 million worldwide, is the third major outbreak caused by zoonotic transmission of a beta-coronavirus (beta-CoV) in the past 20 years. The causative pathogen of COVID-19 is Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which is related to SARS-CoV and Middle East Respiratory Syndrome coronavirus (MERS-CoV), the CoVs responsible for the 2002 and 2012 pandemics, respectively. Although the origin of SARS-CoV-2 is still under investigation, bats have been identified as the natural reservoir for SARS-CoV and MERS-CoV, and transmission to humans required intermediate hosts, such as civets and camels. Various CoV strains are known to cause disease in other animal species, and only a few mutations are necessary to allow transmission to humans, posing the risk of future CoV pandemics. For example, two recent reports demonstrated the transmission to humans of an alpha-CoV, which typically infects dogs, and a delta-CoV, known to infect pigs. Once a zoonotic CoV strain has spread to humans with a sufficient number of human hosts (as is evident in the case of SARS-CoV-2), the virus continues to evolve, leading to the emergence of new variants that may be resistant to vaccines and therapeutics (a major concern for many recently identified SARS-CoV-2 variants of concern).

[0005] To help prevent future CoV pandemics and to protect against emerging SARS-CoV-2 VOCs, two types of vaccine technologies are needed: i) rapid-response vaccines and ii) universal CoV vaccines. Rapid-response vaccines can be developed immediately upon detection of human transmission of a particular CoV and are specific for newly identified CoV strains or variants. This type of vaccine requires rapid, scalable, and adaptable technologies that enable production and ensure rapid global distribution. During the COVID-19 pandemic, mRNA vaccines have emerged as an ideal platform for developing rapid-response vaccines. The mRNA vaccines produced by Pfizer and Moderna encode the SARS-CoV-2 spike (S) protein, the primary target of antibody responses during natural infection. Clinical studies have demonstrated that mRNA vaccines are highly effective, preventing symptomatic and severe SARS-CoV-2 infections in >90% of cases. However, preclinical and clinical studies have shown that neutralizing antibody titers induced by mRNA vaccines are approximately 10-fold lower than those induced by protein nanoparticle (NP)-based vaccines. This is becoming a concern with the emergence of VOCs (e.g., delta, omicron, and their BA.2 subvariants) that are up to 10-fold less susceptible to antibodies induced by mRNA vaccines. Therefore, there is a need to develop rapid-response vaccine technologies that achieve robust neutralizing antibody responses to prevent viral escape and ensure continued protection during ongoing and future CoV pandemics.

[0006] In contrast to rapid-response vaccines, the goal of a universal CoV vaccine is to confer broad immunity against a wide range of CoV strains and their potential variants before human transmission occurs. Broad immunity can be achieved by inducing immune responses against portions of the virus that are conserved among CoVs and their potential variants. Even a weak immune response elicited by a universal CoV vaccine may be sufficient to prevent severe infection and rapid spread after future zoonotic transmission events and / or the emergence of new variants. A mosaic protein NP displaying the receptor-binding domain (RBD), a portion of the S protein that interacts with host receptors for cell entry, from eight SARS-like beta-CoV strains has been shown to elicit heterogeneous antibody responses against beta-CoV strains not displayed on the mosaic protein. However, this strategy is likely limited to closely related strains because the RBD is not widely conserved among the CoV family. Because other parts of the S protein (e.g., the N-terminal domain and S2 domain) are more conserved than the RBD, there is a need for a universal vaccine that presents the entire S protein of various CoV strains and is more effective. Therefore, a universal vaccine technology is needed that generates densely coated NPs for a wide range of CoV S proteins without requiring extensive protein engineering steps. Summary of the Invention [Means for solving the problem]

[0007] The present application discloses compositions (e.g., vaccine compositions). In some embodiments, the compositions include a nucleic acid composition comprising a polynucleotide encoding a fusion protein, wherein the fusion protein comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD), and wherein multiple fusion proteins are capable of self-assembly into enveloped nanoparticles (ENPs) that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs.

[0008] The present application discloses compositions (e.g., vaccine compositions). In some embodiments, the compositions include: a nucleic acid composition comprising n polynucleotides each encoding n fusion proteins, where n is an integer from 2 to 500, wherein each fusion protein comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD), wherein at least two of the fusion proteins differ with respect to the AP; and wherein multiple fusion proteins are capable of self-assembly into enveloped nanoparticles (ENPs) that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs.

[0009] In some embodiments, the fusion protein can be displayed on the surface of a cell expressing the fusion protein. In some embodiments, self-assembly of ENPs: does not require exogenous nucleic acid other than the nucleic acid composition, does not require any exogenous components other than the fusion proteins, and / or requires only a single component (e.g., the fusion protein). In some embodiments, the cells are: cells of a subject; in vivo, ex vivo, or in situ; and / or adherent or suspension cells.

[0010] In some embodiments, upon secretion from the subject's cells, the ENPs are capable of distribution within one or more tissues of the subject (e.g., adrenal tissue, appendix tissue, bladder tissue, bone, intestinal tissue, brain tissue, breast tissue, bronchus, coronary tissue, ear tissue, esophageal tissue, eye tissue, gallbladder tissue, reproductive tissue, heart tissue, hypothalamus tissue, kidney tissue, large intestine tissue, intestinal tissue, laryngeal tissue, liver tissue, lung tissue, lymph node, oral tissue, nasal tissue, pancreatic tissue, parathyroid tissue, pituitary tissue, prostate tissue, rectal tissue, salivary gland tissue, skeletal muscle tissue, skin tissue, small intestine tissue, spinal cord, spleen tissue, stomach tissue, thymus tissue, tracheal tissue, thyroid tissue, ureteral tissue, urethral tissue, soft and connective tissue, peritoneal tissue, vascular tissue, adipose tissue, or any combination thereof). In some embodiments, the ENPs engage multiple immune cells in the one or more tissues, thereby mimicking a natural infection.

[0011] The present application discloses compositions (e.g., vaccine compositions). In some embodiments, the compositions include a population of ENPs, where each of the ENPs comprises a plurality of fusion proteins, each comprising an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD).

[0012] In some embodiments, the ENP is derived from expression of a nucleic acid composition provided herein. In some embodiments, the ENP comprises a lipid bilayer (e.g., a lipid bilayer derived from the cell that secreted the ENP). In some embodiments, the ERD recruits one or more ESCRT proteins to the cytoplasmic tail of the fusion protein. In some embodiments, recruitment of ESCRT proteins via the ERD induces self-assembly and budding of ENPs. In some embodiments, the cytoplasmic portion of the fusion protein comprises the ERD. In some embodiments, the cytoplasmic tail of the fusion protein comprises the ERD. In some embodiments, the ERD interacts with the ESCRT proteins TSG101, NEDD4, and / or ALIX.

[0013] In some embodiments, the ERD comprises or is derived from a non-human protein, optionally a non-mammalian protein, further optionally a chicken protein, a mouse protein, a lizard protein, a reptile protein, a hamster protein, or a goldfish protein. In some embodiments, the ERD comprises or is derived from the ESCRT and ALIX binding region (EABR) of the human CEP55 protein, optionally residues 170 to 213. In some embodiments, the ERD comprises or is derived from syntenin-1, rat galectin-3 (rGalectin-3), Hrs, and / or CD2AP. In some embodiments, the ERD comprises or is derived from a viral protein, optionally a fragment of a viral protein, further optionally a retrovirus protein, a herpes simplex virus protein, a vaccinia virus protein, a hepadnavirus protein, a togavirus protein, a flavivirus protein, an arenavirus protein, a coronavirus protein, an orthomyxovirus protein, a paramyxovirus protein, a bunyavirus protein, a bornavirus protein, a rhabdovirus protein, or a filovirus protein, optionally a Gag protein, further optionally a Gag protein from EIAV, HTLV-1, MLV, or MPMV, optionally a Gag protein from EIAV p9 and / or HIV-1 p6, hi some embodiments, the ERD comprises or is derived from an Ebola protein, optionally EBOV VP40. In some embodiments, the ERD comprises an amino acid sequence having at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 20 and 23.

[0014] In some embodiments, the fusion protein comprises an endocytosis-preventing motif (EPM) that can prevent endocytosis of the fusion protein. In some embodiments, the EPM: tethers the fusion protein to the cytoskeleton, thereby preventing localization to coated pits and endocytosis; enhances ENP assembly, ENP production, and / or ENP secretion; and / or prevents endocytosis of the fusion protein, thereby extending the time the fusion protein remains at the plasma membrane and interacts with ESCRT proteins. In some embodiments, the EPM: increases the abundance and / or density of the fusion protein on and / or in the ENPs by at least about two-fold compared to ENPs comprising the fusion protein without the EPM; and / or increases the number of ENPs secreted by cells by at least about two-fold compared to cells expressing the fusion protein without the EPM. In some embodiments, the EPM comprises or is derived from a portion of the murine low-affinity gamma Fc region receptor II isoform FcRII-B1. In some embodiments, the EPM comprises all or a portion of the cytoplasmic tail of FcRII-B1. In some embodiments, the EPM comprises an amino acid sequence having at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 21.

[0015] In some embodiments, the AP, or a portion thereof, is displayed within and / or on the surface of the ENP. In some embodiments, the AP is from about 1 amino acid to about 10,000 amino acids in length. In some embodiments, the AP comprises or is derived from an antigenic protein associated with a disease or disorder, optionally an immunogenic variant and / or immunogenic fragment of the antigenic protein. In some embodiments, the AP comprises or is derived from a conserved portion of the antigenic protein. In some embodiments, the AP is present on and / or in the ENP in its native membrane-bound conformation.

[0016] In some embodiments, the AP comprises or is derived from at least about 5% of the full length of the antigenic protein, optionally, the AP comprises or is derived from a full length surface protein of an infectious agent.

[0017] In some embodiments, the disease or disorder is an infectious disease or disorder caused by an infectious agent, wherein the AP comprises or is derived from an antigenic protein of the infectious agent, and wherein the antigenic protein of the infectious agent is a pathogenic antigen. In some embodiments, the disease or disorder is a disease associated with expression of a tumor-associated antigen, and wherein the antigenic protein is a tumor-associated antigen. In some embodiments, the disease or disorder is an autoimmune disease or disorder, and wherein the antigenic protein is an autoimmune antigen. In some embodiments, the disease or disorder is an allergic disease or disorder, and wherein the antigenic protein is an allergic antigen.

[0018] The infectious agent is a bacterium, a fungus, a virus, or a protist. In some embodiments, the infectious agent is a coronavirus (CoV) (e.g., an alphacoronavirus, a betacoronavirus, a gammacoronavirus, or a deltacoronavirus). In some embodiments, the infectious agent is Acinetobacter baumannii, Anaplasma genus, Anaplasma phagocytophilum, Ancylostoma braziliense, Ancylostoma duodenale, Arcanobacterium haemolyticum, Ascaris lumbricoides, Aspergillus genus, Astroviridae, Babesia genus, Bacillus anthracis, Bacillus cereus, Bartonella henselae, or any of the following: henselae, BK virus, Blastocystis hominis, Blastomyces dermatitidis, Bordetella pertussis, Borrelia burgdorferi, Borrelia genus, Borrelia spp, Brucella genus, Brugia malayi, Bunyaviridae, Burkholderia cepacia and other Burkholderia spp, Burkholderia mallei, Burkholderia pseudomallei, Caliciviridae, Campylobacter spp, Candida albicans, Candida spp. spp), Chlamydia trachomatistrachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, CJD prion, Clonorchis sinensis, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium perfringens, Clostridium spp., Clostridium tetani, Coccidioides spp., coronaviruses, Corynebacterium diphtheriae, Coxiella burnetii burnetii, Crimean-Congo hemorrhagic fever virus, Cryptococcus neoformans, Cryptosporidium spp., Cytomegalovirus (CMV), Dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4), Dientamoeba fragilis, Ebola virus (EBOV), Echinococcus spp., Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia genus, Entamoeba histolytica, Enterococcus spp., Enterovirus spp., Enteroviruses, mainly Coxsackie A virus and Enterovirus 71 (EV71), Epidermophyton spp., Epstein-Barr virus (EBV), Escherichia coli O157:H7, O111, and O104:H4, Fasciola hepatica and Fasciola gigantica, FFI prion, Filarioidea superfamily, Filoviruses, Flaviviruses, Francisellatularensis, Fusobacterium genus, Geotrichum candidum, intestinal Giardia, Gnathosoma species, GSS prion, Guanarito virus, Haemophilus ducreyi, Haemophilus influenzae, Helicobacter pylori, Henipavirus (Hendra virus, Nipah virus), Hepatitis A virus, Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus, Hepatitis E virus, Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), Histoplasma capsulatum, HIV (human immunodeficiency virus), Hortaea wernechii, human bocavirus (HBoV), human herpesvirus type 6 (HHV-6) and human herpesvirus type 7 (HHV-7), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza virus (HPIV), Japanese encephalitis virus, JC virus, Junin virus, Kingella kingae, Klebsiella granulomatis, Kuru prion prion, Lassa virus, Legionella pneumophila, Leishmania spp., Leptospira spp., Listeria monocytogenes, Lymphocytic choriomeningitis virus (LCMV), Machupo virus, Malassezia spp., Marburg virus, Measles virus, Metagonimus yokagawai, Microsporidia, Molluscum contagiosum virus (MCV), Mumps virus, Mycobacterium leprae and Mycobacterium lepromatosis, Mycobacterium tuberculosis, Mycobacterium ulcerans, Mycoplasma pneumoniae, Naegleria fowleri, Necatoramericanus, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Nocardia spp., Onchocerca volvulus, Orientia tsutsugamushi, Orthomyxoviridae (influenza), Paracoccidioides brasiliensis, Paragonimus spp., Paragonimus westermani, Parvovirus B19, Pasteurella spp., Plasmodium spp., Pneumocystis jirovecii, poliovirus, rabies virus, respiratory syncytial virus (RSV), rhinovirus, rhinoviruses, Rickettsia akari, Rickettsia spp., Rickettsia typhi prowazekii, Rickettsia rickettsii, Rickettsia typhi, Rift Valley fever virus, Rotavirus, Rubella virus, Sabia virus, Salmonella genus, Sarcoptes scabiei, SARS coronavirus, Schistosoma genus, Shigella genus, Sin Nombre virus, Hantavirus, Sporothrix schenckii, Staphylococcus genus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes pyogenes, Strongyloides stercoralis, Taenia, Taenia solium, Tick-borne encephalitis virus (TBEV), Toxocara canis or Toxocara cati, Toxoplasma gondiigondii, Treponema pallidum, Trichinella spiralis, Trichomonas vaginalis, Tinea species, Trichuris trichiura, Trypanosoma brucei, Trypanosoma cruzi, Ureaplasma urealyticum, Varicella zoster virus (VZV), Variola major or Variola minor, vCJD prion, Venezuelan equine encephalitis virus, Vibrio cholerae, West Nile virus, Western equine encephalitis virus virus, Wuchereria bancrofti, Yellow fever virus, Yersinia enterocolitica, Yersinia pestis, and Yersinia pseudotuberculosis.

[0019] In some embodiments, the AP comprises a membrane protein (e.g., a multi-spanning transmembrane protein). In some embodiments, the AP is not configured to be a soluble protein. In some embodiments, the AP does not comprise one or more mutations configured to enhance its solubility and / or stability. In some embodiments, the AP does not comprise a transmembrane domain and / or is a soluble protein, and wherein the fusion protein comprises a transmembrane domain (TD). In some embodiments, the transmembrane domain comprises or is derived from a non-human transmembrane protein (e.g., a non-mammalian transmembrane protein). In some embodiments, the TD comprises or is derived from a natural protein, a recombinant protein, and / or a synthetic protein (a synthetic protein comprising primarily hydrophobic residues).

[0020] The fusion protein may comprise one or more linkers. In some embodiments, the one or more linkers comprise one or more flexible amino acid residues, optionally from about 1 to about 18 flexible amino acid residues, and further optionally, the flexible amino acid residues comprise glycine, serine, or a combination thereof. In some embodiments, the one or more linkers are glycine-serine (GS) linkers, optionally from 1 to 15 amino acids in length. In some embodiments, the one or more linkers are located between the ERD and AP, between the ERD and EPM, between the ERD and TD, between the EPM and TD, between the AP and EPM, and / or between the AP and TD.

[0021] In some embodiments, at least two fusion proteins of said plurality of fusion proteins differ from each other with respect to said AP, and wherein said population of ENPs thereby displays a plurality of different APs.

[0022] In some embodiments, the population of ENPs comprises one or more homotypic ENPs, wherein the fusion proteins of the homotypic ENPs are identical to one another with respect to the AP, and wherein the homotypic ENPs do not thereby display multiple different APs. In some embodiments, the population of ENPs comprises one or more heterotypic ENPs, wherein at least two fusion proteins of the heterotypic ENPs differ from one another with respect to the AP, and wherein the heterotypic ENPs thereby display multiple different APs. In some embodiments, the population of ENPs comprises a mixture of two or more homotypic ENPs, wherein the two or more homotypic ENPs differ from one another with respect to the AP of the fusion proteins present in the two or more homotypic ENPs, and wherein the population of ENPs thereby displays multiple different APs. In some embodiments, the population of ENPs comprises a mixture of two or more heterotypic ENPs, wherein the mixture of two or more heterotypic ENPs differs from one another with respect to the AP of the fusion proteins of the two or more heterotypic ENPs. In some embodiments, the heterotypic ENP is capable of eliciting a heterotypic antibody response against an additional infectious agent, and wherein the heterotypic ENP does not display an AP derived from the additional infectious agent.

[0023] The plurality of different APs includes between about 2 and about 500 antigenic polypeptides that differ from each other; APs of the same protein type; and / or APs of different protein types. In some embodiments, the same ENP includes APs from two or more strains of the same family, genus, and / or species of infectious agent. In some embodiments, the plurality of different APs have about, at least, or at least about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity with each other.

[0024] The plurality of different APs comprises a plurality of coronavirus (CoV) antigens, wherein the plurality of CoV antigens comprises a first CoV antigen of a first CoV and a second CoV antigen of a second CoV different from the first CoV. In some embodiments, the plurality of CoV antigens comprises a CoV spike protein (S protein) or a portion thereof, a CoV envelope protein (E protein) or a portion thereof, a CoV nucleocapsid protein (N protein) or a portion thereof, a CoV hemagglutinin-esterase protein (HE protein) or a portion thereof, a CoV papain-like protease or a portion thereof, a CoV 3CL protease or a portion thereof, a CoV membrane protein (M protein) or a portion thereof, or a combination thereof. In some embodiments, the plurality of CoV antigens comprises a CoV S protein or a portion thereof. In some embodiments, the first CoV antigen, the second CoV antigen, or both comprise a CoV S protein or a portion thereof. In some embodiments, the number of first CoV antigen molecules and the number of second CoV antigen molecules is in a ratio of 1:100 to 100:1. In some embodiments, the plurality of CoV antigens comprises three, four, five, six, seven, or eight CoV antigens, wherein each of the CoVs is different from one another. The plurality of CoV antigens further comprises at least a third CoV antigen of a third CoV and a fourth CoV antigen of a fourth CoV, and wherein the first, second, third, and fourth CoVs are different from one another.

[0025] The plurality of different APs includes at least m pathogenic antigens of m infectious agents, where m is an integer greater than 2, and where each m pathogenic antigen is different from each other, optionally where m is an integer greater than 50.In some embodiments, the plurality of different APs includes a first pathogenicity antigen (PA) of a first infectious agent (IA), a second PA of a second IA, a third PA of a third IA, a fourth PA of a fourth IA, a fifth PA of a fifth IA, a sixth PA of a sixth IA, a seventh PA of a seventh IA, an eighth PA of an eighth IA, a ninth PA of a ninth IA, a tenth PA of a tenth IA, an eleventh PA of an eleventh IA, a twelfth PA of a twelfth IA, a thirteenth PA of a thirteenth IA, a fourteenth PA of a fourteenth IA, a fifteenth PA of a fifteenth IA, a sixteenth PA of a sixteenth IA, a seventeenth PA of a seven ... 17th PA of IA, 18th PA of 18th IA, 19th PA of 19th IA, 20th PA of 20th IA, 21st PA of 21st IA, 22nd PA of 22nd IA, 23rd PA of 23rd IA, 24th PA of 24th IA, 25th PA of 25th IA, 26th PA of 26th IA, 27th PA of 27th IA, 28th PA of 28th IA, 29th PA of 29th IA, 30th PA of 30th IA, 31st PA of 31st IA, 32nd PA of 32nd IA, 33rd PA of 33rd IA, 34th PA of 34th IA, the 35th PA of the 35 IA, the 36th PA of the 36th IA, the 37th PA of the 37th IA, the 38th PA of the 38th IA, the 39th PA of the 39th IA, the 40th PA of the 40th IA, the 41st PA of the 41st IA, the 42nd PA of the 42nd IA, the 43rd PA of the 43rd IA, the 44th PA of the 44th IA, the 45th PA of the 45th IA, the 46th PA of the 46th IA, the 47th PA of the 47th IA, the 48th PA of the 48th IA, the 49th PA of the 49th IA, and the 50th PA of the 50th IA, The third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth, thirteenth, fourteenth, fifteenth, sixteenth, seventeenth, eighteenth, nineteenth, twentieth, twenty-first, twenty-second, twenty-third, twenty-fourth, twenty-fifth, twenty-fifth, twenty-sixth, twenty-seventh, twenty-eighth, twenty-ninth, thirty-first, thirty-second, thirty-third, thirty-fourth, thirty-fifth, thirty-sixth, thirty-seventh, thirty-eighth, thirty-ninth, fortieth ...In some embodiments, the first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth, thirteenth, fourteenth, fifteenth, sixteenth, seventeenth, eighteenth, nineteenth, twentieth, twenty-first, twenty-second, twenty-third, twenty-fourth, twenty-fifth, twenty-sixth, The 27th, 28th, 29th, 30th, 31st, 32nd, 33rd, 34th, 35th, 36th, 37th, 38th, 39th, 40th, 41st, 42nd, 43rd, 44th, 45th, 46th, 47th, 48th, 49th, and 50th infectious agents are different from one another. In some embodiments, the plurality of different APs comprises multiple CoV antigens, multiple influenza antigens, and / or multiple HIV antigens.

[0026] In some embodiments, one or more of the plurality of CoV antigens is a CoV antigen of a CoV in the genus Alpha-CoV and / or of a CoV in the genus Beta-CoV, and optionally, wherein each of the plurality of CoV antigens is a CoV antigen of a CoV in the genus Beta-CoV. In some embodiments, the plurality of CoV antigens are CoV antigens of CoVs in the subgenus Sarbecovirus. In some embodiments, the first CoV and the second CoV belong to the genus Beta-CoV, optionally to the subgenus Sarbecovirus. In some embodiments, the multiple CoV antigens are CoVs selected from the group consisting of SARS-CoV, SARS-CoV-2, WIV1, SHC014, Rf1, RmYN02, pang17, RaTG13, Rs4081, LYRa11, HKU3, Yunnan2011, BtKY72, BM48-31, WIV16, Khosta-1, and Khosta-2. In some embodiments, the first CoV, the second CoV, or both are selected from the group consisting of SARS-CoV, SARS-CoV-2, WIV1, SHC014, Rf1, RmYN02, pang17, RaTG13, Rs4081, LYRa11, HKU3, Yunnan2011, BtKY72, BM48-31, WIV16, Khosta-1, and Khosta-2. In some embodiments, the CoV is selected from species or subspecies of SARS-CoV, SARS-CoV-1, SARS-CoV-2, MERS-CoV, SL-CoV-WIVl, HKU4, HKU5, HCoV-OC43, HCoV-HKUl, HKU9, HKU3, HKU8, HKU24, NL63, SHC014, 229E, and / or SARS-CoV-2 variants B.1.351, B.1.1.7, P.1, B.1.617.2, B.1.1.529, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and other descendant lineages.In some embodiments, the CoV is selected from a species or subspecies of Embecovirus, Sarbecovirus, Merbecovirus, Nobevovirus, Hibecovirus, SARSr-CoV, MERS-CoV, or any combination thereof. In some embodiments, the CoV is selected from a Beta-CoV from the sarbeco-, enbeco-, merbeco-, and / or nobecovirus lineages. In some embodiments, the CoV is selected from a sarbecovirus strain, optionally SARS, LYRa11, Rf1, Rs4081, BtKY72, and / or BM48-31. In some embodiments, the CoV is a Merobecovirus strain, optionally selected from HKU4, HKU5, HKU25, BtCoV-Vs-CoV1, MERS-associated NL13845, MERS-associated NL140422. In some embodiments, the CoV is an Envecovirus strain, optionally selected from HKU1, Rat CoV Parker, PHEV, Equine CoV, Rodent CoV, Longquan Rat CoV.

[0027] In some embodiments, the ENP comprises at least about 2-fold more of the AP and / or is at least as immunogenic as a multi-component nanoparticle approach, optionally compared to a SpyCatcher-based nanoparticle approach or a lentiviral Gag-based approach, and further optionally the multi-component nanoparticle approach comprises two or more distinct polypeptides. In some embodiments, the ENP comprises at least about 2-fold more of the AP, at least about 2-fold higher density of the AP, and / or is at least as immunogenic as a nanoparticle approach that does not comprise the ERD, optionally compared to a SpyCatcher-based or Gag-based nanoparticle approach.

[0028] In some embodiments, the nucleic acid composition does not comprise a polynucleotide encoding SpyTag or lentiviral Gag, hi some embodiments, the ENP does not comprise SpyTag or lentiviral Gag.

[0029] In some embodiments, the ENPs have one or more dimensions of eukaryotic viruses. In some embodiments, less than about 10% of the ENPs in the population of ENPs have a particle size smaller than about 10 nm. In some embodiments, less than about 10% of the ENPs in the population of ENPs have a particle size greater than about 80 nm. In some embodiments, the average diameter of the ENPs in the population of ENPs ranges from about 5 nm to about 80 nm, from about 15 nm to about 50 nm, or from about 20 nm to about 40 nm. In some embodiments, the average diameter of the ENPs in the population of ENPs is about 10 nm, about 12 nm, about 14 nm, about 16 nm, about 18 nm, about 20 nm, about 22 nm, about 24 nm, about 26 nm, about 28 nm, about 30 nm, about 32 nm, about 34 nm, about 36 nm, about 38 nm, about 40 nm, about 42 nm, about 44 nm, about 46 nm, about 48 nm, or about 50 nm; optionally, the average is the mean, median, or mode; optionally, the mean is the arithmetic mean, geometric mean, and / or harmonic mean. In some embodiments, the ENPs have a minimum diameter of about 10 nm, about 12 nm, about 14 nm, about 16 nm, about 18 nm, about 20 nm, about 22 nm, about 24 nm, about 26 nm, about 28 nm, about 30 nm, about 32 nm, about 34 nm, about 36 nm, about 38 nm, about 40 nm, about 42 nm, about 44 nm, about 46 nm, about 48 nm, or about 50 nm.In some embodiments, the ENP is about 10 nm, about 12 nm, about 14 nm, about 16 nm, about 18 nm, about 20 nm, about 22 nm, about 24 nm, about 26 nm, about 28 nm, about 30 nm, about 32 nm, about 34 nm, about 36 nm, about 38 nm, about 40 nm, about 42 nm, about 44 nm, about 46 nm, about 48 nm, about 50 nm. nm, about 52 nm, about 54 nm, about 56 nm, about 58 nm, about 60 nm, about 62 nm, about 64 nm, about 66 nm, about 68 nm, about 70 nm, about 72 nm, about 74 nm, about 76 nm, about 78 nm, or about 80 nm.

[0030] In some embodiments, the ENPs are derived from cell cultures transiently transfected with the nucleic acid composition, optionally by ultracentrifugation and / or size-exclusion chromatography, further optionally by ultracentrifugation on a 20% sucrose cushion, wherein the cell cultures have optionally been transfected by calcium phosphate transfection, DEAE-dextran-mediated transfection, cationic lipid-mediated transfection, electroporation, electrical nuclear transport, chemical transduction, electrotransduction, lipofectamine-mediated transfection, Effectene-mediated transfection, lipid nanoparticle (LNP)-mediated transfection, or any combination thereof. In some embodiments, storage of the ENPs at 4° C. for at least 3 months reduces immunogenicity by less than about 50%. In some embodiments, the composition is stable for at least about 2 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, or about 1 year after storage as a liquid at a temperature of about 4° C. In some embodiments, at least about 70%, 75%, 80%, 85%, 90%, or 95% of the ENPs are immunogenic for at least 1 month after storage as a liquid at a temperature of about 5° C.

[0031] In some embodiments, the nucleic acid composition is complexed or associated with one or more lipids or lipid-based carriers, thereby forming liposomes, lipid nanoparticles (LNPs), lipoplexes, and / or nanoliposomes, optionally encapsulating the nucleic acid composition. In some embodiments, the nucleic acid composition is, comprises, or further comprises one or more vectors. In some embodiments, at least one of the one or more vectors is a viral vector, a plasmid, a transposable element, a naked DNA vector, a lipid nanoparticle (LNP), or any combination thereof. In some embodiments, the viral vector is an AAV vector, a lentiviral vector, a retroviral vector, an adenoviral vector, a herpes virus vector, a herpes simplex virus vector, a cytomegalovirus vector, a vaccinia virus vector, an MVA vector, a baculovirus vector, a vesicular stomatitis virus vector, a human papillomavirus vector, an avipox virus vector, a Sindbis virus vector, a VEE vector, a measles virus vector, an influenza virus vector, a hepatitis B virus vector, an integration-deficient lentiviral (IDLV) vector, or any combination thereof. In some embodiments, the transposable element is a piggybac transposon or a sleeping beauty transposon.

[0032] In some embodiments, the polynucleotides encoding the fusion proteins are contained in one or more vectors. In some embodiments, the polynucleotides encoding the fusion proteins are contained in the same vector and / or in different vectors. In some embodiments, the polynucleotides encoding the fusion proteins are present on the same nucleic acid and / or on different nucleic acids.

[0033] In some embodiments, the one or more vectors are DNA vaccines. In some embodiments, the polynucleotide encoding the fusion protein is operably linked to one or more promoters capable of directing transcription of the polynucleotide. In some embodiments, the DNA vaccine is a plasmid-based DNA vaccine, a minicircle-based DNA vaccine, a bacmid-based DNA vaccine, a minigene-based DNA vaccine, a ministring DNA (linear covalently closed DNA vector) vaccine, a closed-ended linear duplex DNA (CELiD or ceDNA) vaccine, a doggybone vaccine, or a genomic DNA vaccine. TM The DNA vaccine is a DNA vaccine, a dumbbell-shaped DNA vaccine, or a minimalistic immunologically-defined gene expression (MIDGE)-vectored DNA vaccine. In some embodiments, the DNA vaccine elicits at least a two-fold higher neutralizing antibody response against the infectious agent compared to a DNA vaccine encoding the AP but not the ERD.

[0034] In some embodiments, the promoter comprises a ubiquitous promoter, an inducible promoter, a tissue-specific promoter, and / or a lineage-specific promoter. In some embodiments, the ubiquitous promoter is a cytomegalovirus (CMV) immediate early promoter, a CMV promoter, simian virus 40 (SV40) (e.g., early or late), Moloney murine leukemia virus (MoMLV) LTR promoter, Rous sarcoma virus (RSV) LTR, an RSV promoter, herpes simplex virus (HSV) (thymidine kinase) promoter, H5, P7.5, and P11 promoters from vaccinia virus, elongation factor 1-alpha (EF1a) promoter, early growth response 1 (EGR1), ferritin H (FerH), ferritin L (FerL), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), eukaryotic translation initiation factor 4A1 (EIF4A1), heat shock 70 kDa protein 5 (HSPA5), heat shock protein 90 (HSP1), or the like. kDa beta, member 1 (HSP90B1), heat shock protein 70 kDa (HSP70), beta-kinesin (β-KIN), human ROSA 26 locus, ubiquitin C promoter (UBC), phosphoglycerate kinase-1 (PGK) promoter, 3-phosphoglycerate kinase promoter, cytomegalovirus enhancer, human beta-actin (HBA) promoter, chicken beta-actin (CBA) promoter, CAG promoter, CASI promoter, CBH promoter, or any combination thereof.

[0035] In some embodiments, the polynucleotide encoding the fusion protein is operably linked to a tandem gene expression element (e.g., an internal ribosome entry site (IRES), foot-and-mouth disease virus 2A peptide (F2A), equine rhinitis A virus 2A peptide (E2A), porcine teschovirus 2A peptide (P2A), or Thosea asigna virus 2A peptide (T2A), or any combination thereof). In some embodiments, the polynucleotide encoding the fusion protein comprises a transcript stabilization element (e.g., a woodchuck hepatitis post-translational regulatory element (WPRE), a bovine growth hormone polyadenylation (bGH-polyA) signal sequence, a human growth hormone polyadenylation (hGH-polyA) signal sequence, or any combination thereof).

[0036] In some embodiments, the nucleic acid composition is or comprises mRNA. In some embodiments, the mRNA is formulated in a lipid nanoparticle (LNP). In some embodiments, the mRNA comprises a 5' untranslated region (UTR), a 3' UTR, and / or a CAP. In some embodiments, the mRNA comprises one or more modified nucleotides selected from the group including pseudouridine, N-1-methyl-pseudouridine, 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, O(6)-methylguanine, and 2-thiocytidine. In some embodiments, the mRNA comprises one or more modified nucleotides in place of uridine. In some embodiments, the modified nucleoside is selected from pseudouridine (ψ), N 1-methyl-pseudouridine (m 1Ψ), and 5-methyl-uridine (m5U).

[0037] In some embodiments, the LNPs comprise one or more of an ionizable cationic lipid, a non-cationic lipid, a sterol, and a PEG-modified lipid, and optionally, the non-cationic lipid is a neutral lipid. In some embodiments, the LNPs comprise 0.5-15 mol% PEG-modified lipid, 5-25 mol% non-cationic lipid, 25-55 mol% sterol, and 20-60 mol% ionizable cationic lipid. In some embodiments, the LNPs comprise 40-55 mol% ionizable cationic lipid, 5-15 mol% neutral lipid, 35-45 mol% sterol, and 1-5 mol% PEG-modified lipid.

[0038] In some embodiments, the LNP comprises: 47 mol% ionizable cationic lipid, 11.5 mol% neutral lipid, 38.5 mol% sterol, and 3.0 mol% PEG-modified lipid; 48 mol% ionizable cationic lipid, 11 mol% neutral lipid, 38.5 mol% sterol, and 2.5 mol% PEG-modified lipid; 49 mol% ionizable cationic lipid, 10.5 mol% neutral lipid, 38.5 mol% sterol, and 2.0 mol% PEG-modified lipid; 50 mol% ionizable cationic lipid, 10 mol% neutral lipid, 38.5 mol% sterol, and 1.5 mol% PEG-modified lipid; or 51 mol% ionizable cationic lipid, 9.5 mol% neutral lipid, 38.5 mol% sterol, and 1.0 mol% PEG-modified lipid.

[0039] In some embodiments, the ionizable cationic lipid is heptadecan-9-yl 8((2hydroxyethyl)(6oxo6-(undecyloxy)hexyl)amino)octanoate; the neutral lipid is 1,2 distearoyl sn glycero-3 phosphocholine (DSPC); the sterol is cholesterol; and / or the PEG-modified lipid is 1-monomethoxypolyethyleneglycol-2,3-dimyristylglycerol (PEG2000 DMG) having an average molecular weight of 2000 polyethylene glycol. In some embodiments, the wt / wt ratio of lipid:mRNA is about 1:100 to about 100:1.

[0040] In some embodiments, (i) the nucleic acid composition comprises one or more polynucleotides encoding an immunostimulatory factor; and / or (ii) the population of ENPs comprises one or more immunostimulatory factors (e.g., a toll-like receptor (TLR) agonist, a cytokine receptor agonist, a CD40 agonist, an Fc receptor agonist, a CpG-containing nucleic acid, a complement receptor agonist, or any combination thereof). In some embodiments, the TLR agonist is a TLR-1 agonist, a TLR-2 agonist, a TLR-3 agonist, a TLR-4 agonist, a TLR-5 agonist, a TLR-6 agonist, a TLR-7 agonist, a TLR-8 agonist, a TLR-9 agonist, and / or a TLR10 agonist; the Fc receptor agonist is an Fc-gamma receptor agonist; the complement receptor agonist binds to CD21 or CD35; the complement receptor agonist induces endogenous complement opsonization of the ENP; the cytokine receptor agonist is a cytokine; and / or the cytokine receptor agonist is a small molecule, an antibody, a fusion protein, or an aptamer.

[0041] In some embodiments, the composition comprises Tris buffer, sucrose, and / or sodium acetate. In some embodiments, the composition comprises an adjuvant (e.g., aluminum hydroxide, Alhydrogel, AddaVax, MF59, AS03, Freund's adjuvant, Montanide ISA51, CpG, poly I:C, glucopyranosyl lipid A, flagellin, resiquimod, or any combination thereof). In some embodiments, the composition is a lyophilized composition. In some embodiments, the lyophilized composition has a moisture content of less than about 10%.

[0042] In some embodiments, the composition is formulated, or will be formulated, as a liquid, a solid, or a combination thereof; for injection; for intramuscular administration, intranasal administration, transdermal administration, aerosol delivery, nasal delivery, vaginal delivery, rectal delivery, buccal delivery, ocular delivery, local delivery, topical delivery, intracisternal delivery, intraperitoneal delivery, oral delivery, intramuscular injection, intravenous injection, subcutaneous injection, intranodal injection, intratumoral injection, intraperitoneal injection, or intradermal injection; and / or as particles (e.g., iron oxide particles, liposomes, micelles, polymer complexes, cationic peptide nanoemulsions, virus-like particles (VLPs), lipid nanoparticles (LNPs), and / or lipoplex (LPX) particles). In some embodiments, the nucleic acid composition and the LNP-forming components are in separate vials.

[0043] In some embodiments, the composition is a pharmaceutical composition, wherein the pharmaceutical composition comprises one or more pharmaceutically acceptable carriers, diluents, and / or excipients. In some embodiments, the composition comprises instructions for using the composition to: stimulate an immune response in a subject, wherein the subject is in need thereof; treat or prevent a disease or disorder caused by an infectious agent, wherein the subject is in need thereof; and / or treat or prevent a CoV infection in a subject, wherein the subject is in need thereof.

[0044] The inventions disclosed herein include kits. In some embodiments, the kits include compositions (e.g., nucleic acid compositions, populations of ENPs) disclosed herein. The inventions disclosed herein include cells. In some embodiments, the cells include nucleic acid compositions disclosed herein.

[0045] The inventions disclosed herein include methods of stimulating an immune response in a subject in need thereof. In some embodiments, the method includes administering to the subject a pharmaceutically effective amount of a composition (e.g., a nucleic acid composition, a population of ENPs) disclosed herein, thereby stimulating an immune response in the subject.

[0046] The inventions disclosed herein include methods of treating or preventing a disease or disorder, wherein the subject is in need thereof. In some embodiments, the method comprises administering to the subject a pharmaceutically effective amount of a composition (e.g., a nucleic acid composition, a population of ENPs) disclosed herein, thereby treating or preventing the disease or disorder in the subject. In some embodiments, the disease or disorder is a disease or disorder caused by an infectious agent. In some embodiments, the disease or disorder caused by an infectious agent is a disease or disorder caused by a coronavirus (CoV) infection.

[0047] The inventions disclosed herein include methods for treating or preventing a coronavirus (CoV) infection in a subject in need thereof. In some embodiments, the method includes administering to the subject a pharmaceutically effective amount of a composition (e.g., a nucleic acid composition, a population of ENPs) disclosed herein, thereby treating or preventing a coronavirus (CoV) infection in the subject.

[0048] In some embodiments, immunogenic levels of the fusion protein and / or ENP are generated in the subject's serum from about 1 hour to about 6 months after administration of the composition. In some embodiments, a neutralizing antibody titer of about 50 to about 100,000 at half-maximal inhibitory dilution (ID50 value) is generated in the subject's serum from about 1 hour to about 6 months after administration of the composition. In some embodiments, the composition elicits at least about two-fold fewer off-target immune responses against undesired epitopes compared to non-enveloped NP-based compositions. In some embodiments, the undesired epitopes comprise the NP scaffold of the non-enveloped NP-based composition. In some embodiments, the method includes administering at least two doses of the composition to the subject. In some embodiments, the second dose of the composition is administered to the subject at least 14 days after administration of the first dose of the composition to the subject.

[0049] In some embodiments, administering the composition induces a neutralizing response to: the infectious agent from which the antigenic polypeptide is derived; and / or an additional infectious agent from which the antigenic polypeptide is not derived, optionally the additional infectious agent is a first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth, thirteenth, fourteenth, fifteenth, sixteenth, is different from the seventeenth, eighteenth, nineteenth, twentieth, twenty-first, twenty-second, twenty-third, twenty-fourth, twenty-fifth, twenty-sixth, twenty-seventh, twenty-eighth, twenty-ninth, thirty-first, thirty-second, thirty-third, thirty-fourth, thirty-fifth, thirty-sixth, thirty-seventh, thirty-eighth, thirty-ninth, fortieth ...

[0050] In some embodiments, administering the composition induces a neutralizing response to a coronavirus, wherein the plurality of coronavirus antigens belong to: a first, a second, a third, a fourth, a fifth, a sixth, a seventh, an eighth, a ninth, a tenth, an eleventh, a twelfth, a thirteenth, a fourteenth, a fifteenth, a sixteenth, a seventeenth, an eighteenth, a nineteenth, a twentieth, a twenty-first, a twenty-second, a twenty-third, a twenty-fourth, a twenty-fifth, a twenty-fifth, a twenty-fifth, a twenty-third, a twenty-fifth, a twenty-fifth, a twenty-third, a twenty-fifth, a twenty-fifth, a twenty-third, a twenty-fifth, a twenty-fifth, a twenty-fifth, a twenty-fifth, a twenty-fifth, a twenty-first, a twenty-second, a twenty-third, a twenty-fourth, a twenty-fifth, a twenty-fifth, a twenty-fifth, a twenty-fifth, a twenty-first, a twenty-third ... a coronavirus different from CoV 6, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and / or 50; and / or a further coronavirus different from the coronavirus to which the plurality of coronavirus antigens belong.

[0051] In some embodiments, administering the composition treats or prevents: an infection caused by a coronavirus different from the first coronavirus and the second coronavirus; an infection caused by an additional coronavirus different from the coronavirus to which the multiple coronavirus antigens belong; an infection caused by a coronavirus to which the multiple coronavirus antigens belong; a disease or disorder caused by a coronavirus different from the first coronavirus and the second coronavirus; a disease or disorder caused by an additional coronavirus different from the coronavirus to which the multiple coronavirus antigens belong; and / or a disease or disorder caused by a coronavirus to which the multiple coronavirus antigens belong. In some embodiments, the composition elicits neutralizing antibody titers that are at least two-fold higher than approaches comprising administering (i) a soluble form of the AP and / or (ii) an mRNA vaccine encoding the AP but not the ERD. In some embodiments, the composition elicits neutralizing antibody titers that are at least as high as approaches comprising administering protein-based nanoparticles displaying the AP. In some embodiments, administration of the composition elicits protective and long-lasting immunity against infectious agents and their variants.

[0052] In some embodiments, at least about a two-fold lower dose of the composition is required to generate an equivalent immune response compared to approaches involving administration of protein-based nanoparticles displaying the AP, and in some embodiments, at least about a two-fold lower dose of the composition is required to generate an equivalent immune response compared to approaches involving administration of (i) a soluble form of the AP and / or (ii) an mRNA vaccine encoding the AP but not the ERD.

[0053] In some embodiments, after administration of the first or second dose of the composition, the composition induces: (i) at least as strong a serum neutralization titer against the infectious agent or a variant thereof as compared to an approach comprising administration of protein-based nanoparticles displaying the AP, optionally wherein the composition comprises a population of ENPs; (ii) at least two-fold stronger serum neutralization titer against the infectious agent or a variant thereof as compared to an approach comprising administration of a soluble form of the AP, optionally wherein the composition comprises a population of ENPs; and / or (iii) at least two-fold stronger serum neutralization titer against the infectious agent or a variant thereof as compared to an approach comprising administration of an mRNA vaccine encoding the AP and not the ERD, optionally wherein the composition comprises an mRNA vaccine encoding a fusion protein comprising the AP. In some embodiments, serum neutralization potency is measured by the geometric mean of the half-maximal inhibitory dilution (ID50 value) against the infectious agent or a variant thereof, optionally from about 1 day to about 6 months after administration of a first dose of the composition, or from about 1 day to about 6 months after administration of a second dose of the composition.

[0054] In some embodiments, the subject: is a human subject; is a newborn or infant aged 3 years or less, 2 years or less, 1.5 years or less, 1 year or less (12 months), 9 months, 6 months, or 3 months or less, or is between 6 months and 2 years of age; is immunocompromised, has pulmonary disease, and / or is 65 years of age or older; has chronic pulmonary disease, optionally chronic obstructive pulmonary disease (COPD) or asthma; and / or has an underlying co-morbidity, optionally the underlying co-morbidity is selected from heart disease, diabetes, and pulmonary disease.

[0055] In some embodiments, the composition is administered in an amount effective to: (i) induce a robust antibody response against the AP in the subject, optionally wherein the robust antibody response comprises a neutralizing antibody response, and optionally wherein the robust antibody response recruits immune cells against infected cells, including Fc domain effector function, optionally wherein the immune cells are macrophages, neutrophils, and / or natural killer cells, and optionally wherein the recruitment induces antibody-dependent cellular cytotoxicity (ADCC) and / or antibody-dependent cellular phagocytosis (ADCP); (ii) induce a robust CD4 and / or CD8 T cell response against the AP in the subject; and / or (iii) induce a balanced Thl / Th2 response against the AP in the subject. In some embodiments, the composition: (i) is co-administered with an adjuvant; or (ii) is not co-administered with an adjuvant.

[0056] In some embodiments, the disease or disorder is a hematological disease, an immune disease, a neurological disease or disorder, cancer, an infectious disease, a genetic disease, a disorder caused by abnormal mtDNA, a metabolic disease, a disorder caused by abnormal cell cycle, a disorder caused by abnormal angiogenesis, a solid tumor, a disorder caused by abnormal DNA damage repair, or any combination thereof.

[0057] In some embodiments, the disease or disorder is acute flaccid myelitis (AFM), anaplasmosis, anthrax, babesiosis, botulism, brucellosis, campylobacteriosis, carbapenem-resistant infection, chancroid, chikungunya virus infection, chlamydia, ciguatera, difficile infection, perfringens, coccidioidomycosis fungal infection, coronavirus infection, Covid-19 (SARS-CoV-2), Creutzfeldt-Jakob disease / transmissible spongiform encephalopathy, cryptosporidiosis, cyclosporiasis, dengue fever 1, 2, 3, or 4, diphtheria, E. coli infection / Shiga toxin-producing (STEC), Eastern equine encephalitis, hemorrhagic fever (Ebola), ehrlichiosis, encephalitis, arbovirus or parainfectious disease, non-polio enterovirus, D68 enterovirus (EV-D68), giardiasis, glanders, gonorrhea, granuloma inguinale, Haemophilus influenzae type B (Hib or H-flu), Hantavirus pulmonary syndrome (HPS), hemolytic uremic syndrome (HUS), hepatitis A (Hep A), hepatitis B (Hep B), hepatitis C (Hep C), hepatitis D (Hep D), hepatitis E (Hep E), herpes, shingles (Herpes zoster) Zoster (Shingles), Histoplasmosis, Human Immunodeficiency Virus / AIDS (HIV / AIDS), Human Papillomavirus (HPV), Influenza (Flu), Legionellosis (Legionnaires' Disease), Leprosy (Hansens' Disease), Leptospirosis, Listeriosis (Listeria), Lyme Disease, Lymphogranuloma venereum infection (LGV), Malaria, Measles, Melioidosis, Meningitis (Viral), Meningococcal Disease (Meningitis (Bacterial)), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mumps, Norovirus, Pediculosis, Pelvic Inflammatory Disease (PID), Pertussis (WhoopingCough), Plague (Bubonic Plague, Septicemic, Pneumonia), Pneumococcal Disease (Pneumonia), Poliomyelitis (Polio), Powassan Encephalitis, Psittacosis, Pthiriasis, Pustular Eruptions (Smallpox, Monkeypox, Cowpox), Q-Fever, Rabies, Rickettsiosis (Rocky Mountain Spotted Fever), Rubella (German Measles) Measles), Salmonellosis Gastroenteritis (Salmonella), Scabies, Scombroid, Sepsis, Severe Acute Respiratory Syndrome (SARS), Shigella Gastroenteritis (Shigella), Smallpox, Staphylococcal Infections Methicillin-Resistant (MRSA), Staphylococcal Food Poisoning Enterotoxin B Poisoning (Staphylococcal Food Poisoning), Staphylococcal Infections Vancomycin-Intermediate Resistant (VISA), Staphylococcal Infections Vancomycin-Resistant (VRSA), Streptococcal Diseases Group A (Invasive) (Strep A (Invasive)), Streptococcal Diseases Group B (Strep-B), Streptococcal Toxic Shock Syndrome (STSS), Syphilis (Primary, Secondary, Early Latent, Late Latent, Congenital), Tetanus Infection, Trichomoniasis, Trichonoses Infection, tuberculosis (TB), latent tuberculosis (LTBI), tularemia, typhoid fever group D, vaginosis, Varicella (Chickenpox), Vibrio cholerae (cholera), vibriosis (Vibrio), Ebola virus hemorrhagic fever, Lasa virus hemorrhagic fever, Marburg virus hemorrhagic fever, West Nile virus, yellow fever, Yersenia, and Zika virus infection.

[0058] In some embodiments, the disease is associated with expression of a tumor-associated antigen (eg, a proliferative disease, a precancerous condition, a cancer, and a non-cancer-related condition associated with expression of a tumor antigen). In some embodiments, the cancer is selected from the group consisting of colon cancer, rectal cancer, renal cell carcinoma, liver cancer, non-small cell carcinoma of the lung, small intestine cancer, esophageal cancer, melanoma, bone cancer, pancreatic cancer, skin cancer, head and neck cancer, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, anal cancer, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, non-Hodgkin's lymphoma, and cancer of the endocrine system. The cancer is selected from the group consisting of: thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, solid tumors of childhood, bladder cancer, kidney and ureter cancer, carcinoma of the renal pelvis, neoplasms of the central nervous system, primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid carcinoma, squamous cell carcinoma, T-cell lymphoma, environmentally induced cancers, combinations of the foregoing cancers, and metastatic lesions of the foregoing cancers.In some embodiments, the cancer is selected from the group consisting of chronic lymphocytic leukemia (CLL), acute leukemia, acute lymphocytic leukemia (ALL), B-cell acute lymphocytic leukemia (B-ALL), T-cell acute lymphocytic leukemia (T-ALL), chronic myeloid leukemia (CML), B-cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia, and myelodysplastic syndrome. and a blood cancer selected from one or more of the following: leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, or pre-leukemia.

[0059] In some embodiments, the administering step comprises aerosol delivery, nasal delivery, vaginal delivery, rectal delivery, buccal delivery, ocular delivery, local delivery, topical delivery, intracisternal delivery, intraperitoneal delivery, oral delivery, intramuscular injection, intravenous injection, subcutaneous injection, intranodal injection, intratumoral injection, intraperitoneal injection, intradermal injection, or any combination thereof. In some embodiments, the composition is administered intramuscularly (e.g., into the deltoid region of the arm). [Brief explanation of the drawings]

[0060] [Figure 1]Figures 1A-1G show data related to the generation of self-assembling SARS-CoV-2 S-EABR NPs (e.g., ENPs). Figure 1A shows a non-limiting, exemplary schematic illustrating the mechanism of the self-assembling S-EABR NP technology. The EABR domain is fused to the cytoplasmic tail of the SARS-CoV-2 S protein and recruits host proteins from the ESCRT pathway, which induces self-assembly and budding of the enveloped S-EABR NPs. Figure 1B shows simplified maps for the SARS-CoV-2 S-p6, S-VP40, S-p9, S-EABR, S-EABRmin1, and S-EABRmin2 constructs. Figure 1C shows representative cryo-electron tomography images showing S-EABR NPs purified by sucrose ultracentrifugation and size-exclusion chromatography. Scale bar = 20 nm. Figure 1D shows Western blot analysis of SARS-CoV-2 S-containing NPs produced by transfecting Expi293 cells with S (lanes 1 and 5), S + Gag (lanes 2 and 6), S + SARS-CoV-2 structural proteins M, N, and E (lanes 3 and 7), or S-EABR (lane 8). NPs were purified from culture supernatants by sucrose ultracentrifugation and size-exclusion chromatography. A 1:20 dilution of the sample was loaded in lanes 1–3 (lane 4 was empty), and a 1:200 dilution was loaded in lanes 5–8. Figure 1E shows Western blot analysis of SARS-CoV-2 S-containing NPs produced and purified by transfecting Expi293 cells with S-p6 (lane 1), S-VP40 (lane 2), S-p9 protein (lane 3), or S-EABR (lane 4). Samples in lanes 1–3 were diluted 1:40, and the S-EABR sample in lane 4 was diluted 1:400. Figure 1F shows Western blot analysis of purified SARS-CoV-2 S-containing NPs produced by transfecting Expi293 cells with S-EABR (lane 1), S fused to two EABR domains (S-2XEABR) (lane 2), or S-EABR containing the Y187A mutation (lanes 3–4).Samples in lanes 1–3 were diluted 1:200, and the sample in lane 4 was diluted 1:20. Figure 1G shows Western blot analysis of SARS-CoV-2 S-containing NPs generated by transfection with S-EABR, S-EABRmin1, and S-EABRmin2. All samples were diluted 1:50. [Figure 2] Figure 2 shows Western blot analysis of SARS-CoV-2 S-containing NPs generated by transfection of S-EABRmin1, muEABRmut1, chicEABRmut1, chicEABRmut2, chamEABRmut1, and goldEABRmut1 (see also Table 1 and Figure 15). Samples were diluted 1:50 or 1:200. [Figure 3] Figures 3A-3D show Western blot analysis of SARS-CoV-2 S-containing NPs generated by transfection with (Figure 3A) S-EABRmin1, S-syntenin-12-60, and Sr-galectin-3; (Figure 3B) S-EABRmin1, Sr-galectin-3, Sr-galectin-3min1, and Sr-galectin-3min2; (Figure 3C) S-EABR, S-Hrs, S-CD2APmin1, and CD2APmin2; and (Figure 3D) S-p6, S-HTLV-1111-130, S-MLV108-177, and S-MPMV197-215. Samples were diluted 1:50, 1:200, or 1:20 as indicated. See Table 2 and Figure 16. [Figure 4]Figures 4A-4C show non-limiting, exemplary data demonstrating that the FcR domain prevents endocytosis and enhances S-EABR NP assembly. Figure 4A shows a simplified map of the SARS-CoV-2 S-EABR and S-FcR-EABR constructs. The amino acid sequences of the FcR and EABR domains are shown. Figure 4B shows a Western blot analysis comparing S-containing NPs after transfection of Expi293 cells with the S-EABR construct (lane 1) or the S-FcR-EABR construct (lane 2). Both samples were diluted 1:200. Figure 4C shows a Western blot analysis of CD4-containing NPs after transfection of Expi293 cells with CD4 (lane 1), CD4 + Gag (lane 2), CD4-EABR (lane 3), or CD4-FcR-EABR (lane 4). All samples were purified by sucrose ultracentrifugation and diluted 1:100. [Figure 5] Figures 5A-5C show non-limiting, exemplary embodiments demonstrating that EABR NPs can be generated for a wide range of membrane proteins. Figure 5A shows the results of Western blot analysis of SARS, HKU1, MERS, and 229E S-EABR NPs purified by sucrose ultracentrifugation and size-exclusion chromatography. All S-EABR constructs were detected by their C-terminal myc-tags, and samples were diluted 1:400. Figure 5B shows Western blot analysis of purified HIV-1 Env-containing NPs generated by transfecting Expi293 cells with HIV-1 Env (lane 1), Env + Gag (lane 2), or Env-EABR (lane 3). All samples were diluted 1:200. Figure 5C shows the results of Western blot analysis of purified CCR5-containing NPs generated by transfecting Expi293 cells with CCR5 (lane 1), CCR5 + Gag (lane 2), or CCR5-EABR (lane 3). All samples were diluted 1:200. [Figure 6]Figures 6A-6F show non-limiting, exemplary data demonstrating that SARS-CoV-2 S-EABR NP induces potent antibody responses in vivo. Figures 6A-6B show SARS-CoV-2 neutralization data for serum samples from C57BL / 6 mice immunized with soluble S, RBD-mi3 NP, and S-EABR NP. Potency is shown as half-maximal inhibitory dilution (ID50) values ​​for (Figure 6A) post-prime (day 14) samples and (Figure 6B) post-boost (day 42) samples. The dashed horizontal line corresponds to the limit of detection. Data points represent the ID50 values ​​of individual animals, and rectangles represent the mean ID50 values ​​for eight animals per group, with SD indicated as a vertical line. Statistical significance (p < 0.05) between groups connected by horizontal lines is indicated with an asterisk. Figure 6C shows the results of a PRNT assay to measure neutralizing activity against authentic SARS-CoV-2 virus in post-boost (day 42) serum samples from C57BL / 6 mice immunized with S-EABR NP. PRNT assays were performed against the early pandemic Wuhan strain as well as beta and delta VOCs. Data points represent the ID50 of individual animals, rectangles represent the mean ID50 for eight animals per group, and SD is shown as a vertical line. Figure 6D shows ELISA data for IgG responses to SARS-CoV-2 S in serum samples from mice immunized with S-2P-EABR NP, S-6P-EABR NP, and S-6P-EABR NP, which were stored at 4°C for 2 months. Serum samples were collected 14 days after a single injection of each immunogen, and results are shown as the area under the curve (AUC) for individual animals. The rectangle represents the mean AUC for 6-8 animals per group, with the SD indicated as a vertical line. Figures 6E-6F show SARS-CoV-2 neutralization for post-boost (day 42) serum samples from BALB / c mice immunized with mRNA vaccines encoding SARS-CoV-2 S or S-EABR NP against the (Figure 6E) Wuhan and (Figure 6F) Omicron variants. Potency is shown as the half-maximal inhibitory dilution (ID50 value).The dashed horizontal line corresponds to the limit of detection. Data points represent the ID50 of individual animals, and rectangles represent the mean ID50 for 10 animals per group, with SD shown as a vertical line. Statistical significance (p < 0.05) between groups connected by horizontal lines is indicated by an asterisk. [Figure 7] Figures 7A-7E show non-limiting, exemplary embodiments of self-assembling S-EABR NPs as a platform technology for developing hybrid mRNA vaccines with enhanced efficacy. Exemplary schematic diagrams of the immune activation mechanisms for S (Figure 7A) and S-EABR (Figure 7B) mRNA vaccines delivered by lipid nanoparticles (LNPs) are shown in Figures 7A-7B. Figure 7C shows post-boost (day 36) neutralization data against SARS-CoV-2 for serum samples from BALB / c mice immunized with 10 μg of S DNA, 10 μg of S-EABR DNA, or 1 μg of purified S-EABR NPs plus adjuvant. Figures 7D-7E show graphs of post-boost (day 42) neutralization of serum samples from C57BL / 6 mice immunized with 1 μg of S mRNA, 1 μg of the S + S-EABR mRNA combination (0.5 μg of S + 0.5 μg of S-EABR), or 1 μg of purified S-EABR NP + adjuvant against (Figure 7D) the SARS-CoV-2 Wuhan strain and (Figure 7E) DeltaVOC. Potency for the data shown in Figures 7C-7E is shown as half-maximal inhibitory dilution (ID50 value). The dashed horizontal line corresponds to the limit of detection. Data points represent the ID50 of individual animals, and rectangles represent the geometric mean ID50 for six animals per group, with the SD indicated by the vertical line. Statistical significance (p < 0.05) between groups connected by horizontal lines is indicated by an asterisk. [Figure 8]Figures 8A-8I show an exemplary embodiment demonstrating the production of S-EABR NP for various CoV strains. Western blot analysis is shown for purified (Figure 8A) SARS-CoV-2 RBD-EABR NP, (Figure 8B) SARS-CoV-2 S-2P-EABR NP (B.1.351 variant), (Figure 8C) SARS-CoV and HKU-1 S-EABR NP, (Figure 8D) Rf1 and HKU-4 S-EABR NP, (Figure 8E) 229E and BtKY72 S-EABR NP, (Figure 8F) MERS-CoV S-EABR NP, and (Figure 8G) NL63 S-EABR NP. Figures 8H-8I show the results of Western blot analysis of purified mosaic S-EABR NPs consisting of (Figure 8H) SARS-CoV, Rf1, BtKY72, HKU-1, HKU-4, and 229E S-EABR, or (Figure 8I) SHC014, HKU-3, HKU-5, HKU-8, HKU-24, and BM48-31 S-EABR. All S-EABR NPs were purified by sucrose ultracentrifugation and size-exclusion chromatography. [Figure 9]Figures 9A-9D show non-limiting, exemplary data demonstrating that mosaic S-EABR NPs induce heterogeneous antibody responses against SARS-CoV-2, MERS-CoV, and SHC014. Figure 9A shows a schematic comparing various approaches to designing a universal CoV vaccine. On the left, a schematic diagram of a homotypic S-EABR NP displaying an S protein from a single CoV strain is shown. The central schematic shows a cocktail of homotypic S-EABR NPs, each displaying an S protein from a single CoV strain. On the right, a heterotypic mosaic S-EABR NP displaying S proteins from multiple CoV strains on the same NP is shown. The ELISAs in Figures 9B-9D show results for post-boost (day 42) serum samples from mice immunized with SARS S-EABR NP, a cocktail (a cocktail of SARS, Rf1, BtKY72, HKU1, HKU4, and 229E S-EABR NP), or a mosaic S-EABR NP generated by co-transfection of SARS, Rf1, BtKY72, HKU1, HKU4, and 229E S-EABR constructs against (Figure 9B) SARS-CoV-2 S and (Figure 9C) MERS-CoV S, as well as (Figure 9D) neutralization data against the lentivirus-based SHC014 pseudovirus. Results are shown for individual animals as area under the curve (AUC) for ELISA and half-maximal inhibitory dilution (ID50 value) for neutralization assay, and rectangles represent the mean values ​​for 8 animals per group, with SD shown as vertical lines. Statistical significance (p < 0.05) between groups connected by horizontal lines is indicated with an asterisk. [Figure 10] Figure 10 shows a non-limiting schematic illustrating the mechanism of the self-assembling S-EABR NP technology compared to traditional approaches that require co-expression of a structural scaffold protein (e.g., Gag) to assemble the NP. [Figure 11]Figures 11A-11B show data on the generation of self-assembled nanoparticles. Figure 11A shows Western blot analysis of SARS-CoV-2 S-containing NPs generated by transfecting Expi293 cells with S (lane 1), S + Gag (lane 2), S + SARS-CoV-2 structural proteins M, N, and E (lane 3), S-EABR (lane 4), or S-FcR-EABR (lane 5). NPs were purified from culture supernatants by sucrose ultracentrifugation. Samples in lanes 1-3 were diluted 1:10, and samples in lanes 4-5 were diluted 1:200. Figure 11B shows Western blot analysis of purified SARS-CoV-2 S-containing NPs produced by transfecting Expi293 cells with S-EABR (lane 1), S fused to EIAV p9 protein (lane 2), S fused to EBOV VP40 protein (lane 3), or S fused to HIV-1 p6 protein (lane 4). The sample in lane 1 was diluted 1:400, and the samples in lanes 2–4 were diluted 1:40. [Figure 12] Figure 12 shows ELISA data for IgG responses to SARS-CoV-2 S for serum samples from mice immunized with S-2P-EABR NP using either Sigma or AddaVax adjuvant. All analyzed serum samples were collected 14 days after a single injection of the respective immunogen, and results are shown as the area under the curve (AUC) for individual animals; rectangles represent the mean AUC for 6-8 animals per group, with SD shown as vertical lines. [Figure 13]Figures 13A-13B show non-limiting, exemplary data demonstrating that mosaic S-EABR NPs induce heterogeneous antibody responses against SARS-CoV-2 and MERS-CoV. ELISA data for IgG responses against (Figure 13A) SARS-CoV-2 S and (Figure 13B) MERS-CoV S are shown for serum samples from mice immunized with SARS-CoV S-EABR NPs, an admix (an admix of SARS-CoV, Rf1, BtKY72, HKU-1, HKU-4, and 229E S-EABR NPs), or mosaic S-EABR NPs generated by co-transfection of SARS-CoV, Rf1, BtKY72, HKU-1, HKU-4, and 229E S-EABR. All analyzed serum samples were collected 14 days after a single injection of each immunogen, and results are shown as the area under the curve (AUC) for individual animals. The rectangles represent the mean AUC for eight animals per group, with SD shown as vertical lines. Statistical significance (p < 0.05) between groups connected by horizontal lines is indicated with an asterisk. [Figure 14] FIG. 14 shows an exemplary schematic illustrating the immune activation mechanism of a potential SARS-CoV-2 S-EABR mRNA vaccine delivered by S-EABR NPs. [Figure 15] 15 shows the amino acid sequences of the EABR domain (EABR, SEQ ID NO: 4) used in this application, as well as muEABRmut1 (SEQ ID NO: 7), chicEABRmut1 (SEQ ID NO: 8), chicEABRmut2 (SEQ ID NO: 9), chamEABRmut1 (SEQ ID NO: 10), and goldEABRmut1 (SEQ ID NO: 11). Residues that differ from the human EABR sequence are in grey text. [Figure 16]Figure 16 shows the amino acid sequences of the ESCRT-binding domains of syntenin-12-60 (SEQ ID NO: 12), rGalectin-3 (SEQ ID NO: 13), rGalectin-3min1 (SEQ ID NO: 14), rGalectin-3min2 (SEQ ID NO: 15), CD2APmin1 (SEQ ID NO: 16), CD2APmin2 (SEQ ID NO: 17), HTLV-1 Gag111-130 (SEQ ID NO: 18), MLV Gag108-177 (SEQ ID NO: 19), and MPMV Gag197-215 (SEQ ID NO: 20).

[0061] [Detailed Description of the Invention] In the following detailed description, reference is made to the accompanying drawings, which form a part of this application. In the drawings, like symbols typically identify like components unless context dictates otherwise. The exemplary embodiments described in this detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described and illustrated in the drawings, may be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are expressly contemplated by and form a part of this disclosure.

[0062] All patents, published patent applications, other publications, and sequences from GenBank and other databases referenced in this application are hereby incorporated by reference in their entirety into this application with respect to the relevant art.

[0063] The present disclosure includes compositions (e.g., vaccine compositions). In some embodiments, the compositions include a nucleic acid composition comprising a polynucleotide encoding a fusion protein, wherein the fusion protein comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD), and wherein multiple fusion proteins are capable of self-assembly into enveloped nanoparticles (ENPs) that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs. In some embodiments, the composition comprises: a nucleic acid composition comprising n polynucleotides each encoding n fusion proteins, where n is an integer from 2 to 500, wherein each fusion protein comprises an AP and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD), wherein at least two of the fusion proteins differ with respect to the AP, and wherein multiple fusion proteins are capable of self-assembly into ENPs that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs. In some embodiments, the composition comprises: a population of ENPs, wherein each of the ENPs comprises multiple fusion proteins, each of which comprises an AP and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD).

[0064] The present disclosure includes kits. In some embodiments, the kits include compositions (e.g., nucleic acid compositions, populations of ENPs) disclosed herein. The present disclosure includes cells. In some embodiments, the cells include nucleic acid compositions disclosed herein.

[0065] The present disclosure includes methods of stimulating an immune response in a subject in need thereof. In some embodiments, the methods include administering to the subject a pharmaceutically effective amount of a composition (e.g., a nucleic acid composition, a population of ENPs) disclosed herein, thereby stimulating an immune response in the subject.

[0066] The present disclosure includes methods of treating or preventing a disease or disorder in a subject in need thereof. In some embodiments, the method includes administering to the subject a pharmaceutically effective amount of a composition (e.g., a nucleic acid composition, a population of ENPs) disclosed herein, thereby treating or preventing the disease or disorder in the subject. In some embodiments, the disease or disorder is a disease or disorder caused by an infectious agent. In some embodiments, the disease or disorder caused by an infectious agent is a disease or disorder caused by a coronavirus (CoV) infection.

[0067] The present disclosure includes methods for treating or preventing a coronavirus (CoV) infection in a subject in need thereof. In some embodiments, the method includes administering to the subject a pharmaceutically effective amount of a composition (e.g., a nucleic acid composition, a population of ENPs) disclosed herein, thereby treating or preventing a CoV infection in the subject.

[0068] definition Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. See, e.g., Singleton et al., Dictionary of Microbiology and Molecular Biology, 2nd ed., J. Wiley & Sons (New York, NY 1994); Sambrook et al., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press (Cold Spring Harbor, NY 1989). For purposes of this disclosure, the following terms are defined below.

[0069] As used in this application, the terms "antigen" and "immunogen" are used interchangeably to refer to a substance, typically a protein, that is capable of inducing an immune response in a subject (e.g., a mammal such as a human). The terms also refer to proteins that are immunologically active in the sense that, when administered to a subject, either directly or in the form of a nucleotide sequence or vector encoding the protein, they are capable of eliciting a humoral and / or cellular immune response against the protein or a variant thereof.

[0070] As used herein, "sequence identity" or "identity" in the context of two nucleic acid or polypeptide sequences refers to the nucleotide bases or residues in the two sequences that are the same when aligned for maximum correspondence over a particular comparison window. Methods for aligning sequences for comparison are well known in the art. For various programs and alignment algorithms, see Smith & Waterman, Adv. Appl. Math. 2:482, 1981; Needleman & Wunsch, J. Mol. Biol. 48:443, 1970; Pearson & Lipman, Proc. Natl. Acad. Sci. USA 85:2444, 1988; Higgins & Sharp, Gene, 73:237-44, 1988; Higgins & Sharp, CABIOS 5:151-3, 1989; Corpet et al., Nuc. Acids Res. 16:10881-90, 1988; Huang et al. Computer Appls. in the Biosciences 8, 155-65, 1992; Pearson et al., Meth. Mol. Bio. 24:307-31, 1994; and Altschul et al., J. Mol. Biol. 215:403-10, 1990, the contents of each of these references being incorporated by reference in their entirety into this application.

[0071] When using percentage sequence identity or sequence similarity in the context of proteins, non-identical residue positions often differ by conservative amino acid substitutions, where the amino acid residue is replaced with a functionally equivalent residue of the original amino acid residue that has similar physiochemical properties, thus preserving the functional properties of the molecule. As used herein, a functionally equivalent residue of an amino acid typically refers to another amino acid residue that has substantially similar physiochemical and stereochemical properties to the original amino acid. These physiochemical properties include water solubility (hydrophobic or hydrophilic), dielectric and electrochemical properties, physiological pH, side chain partial charge (positive, negative, or neutral), and other properties that can be identified by one skilled in the art. These stereochemical properties include the spatial and conformational arrangement of the amino acid and its chirality. For example, glutamic acid is considered a functionally equivalent residue to aspartic acid within the meaning of the present disclosure. Tyrosine and tryptophan are considered functionally equivalent residues to phenylalanine. Arginine and lysine are considered functionally equivalent residues to histidine.

[0072] The term "substantially identical," as used herein in the context of two or more sequences, refers to a certain percentage of amino acid residues or nucleotides that are identical or functionally equivalent, over a particular region, or over the entire sequence (e.g., about, at least, or at least about 65% identical; optionally about, at least, or at least about 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical).

[0073] As used herein, the term "variant" refers to a polynucleotide or polypeptide having a sequence that is substantially similar or identical to a reference (e.g., parent) polynucleotide or polypeptide. In the case of polynucleotides, a variant may have one or more nucleotide deletions, substitutions, or additions at the 5' end, 3' end, and / or one or more internal sites compared to the reference polynucleotide. Sequence similarities and / or differences between a variant and a reference polynucleotide can be detected using conventional techniques known in the art, such as polymerase chain reaction (PCR) and hybridization techniques. Variant polynucleotides also include synthetically derived polynucleotides, such as polynucleotides generated by using site-directed mutagenesis. Generally, a variant of a polynucleotide (e.g., without limitation, DNA) may have at least, or at least about, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to a reference polynucleotide, as determined by sequence alignment programs known in the art. In the case of polypeptides, a variant may have one or more amino acid deletions, substitutions, or additions compared to the reference polypeptide. Sequence similarities and / or differences between a variant and a reference polypeptide may be detected using conventional techniques known in the art, such as Western blot. A variant of a polypeptide may have at least, or at least about, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to a reference polypeptide, for example, as determined by sequence alignment programs known in the art.

[0074] Standard techniques may be used for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (e.g., electroporation, lipofection). Enzymatic reactions and purification techniques may be performed according to manufacturer's specifications or as commonly accomplished in the art, or as described herein. The foregoing techniques and procedures may generally be performed according to conventional methods well known in the art, and as described in the various general and more specific references cited and discussed throughout this specification. See, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual (2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (1989)), which is incorporated by reference into this application for all purposes. Unless specific definitions are provided, the nomenclature used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described in this application are those commonly known and used in the art. Standard techniques may be used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients.

[0075] As used herein, the term "construct" refers to a recombinant nucleic acid that is generated to express a particular nucleotide sequence or that is to be used in constructing other recombinant nucleotide sequences.

[0076] As used herein, the terms "nucleic acid" and "polynucleotide" are interchangeable and refer to any nucleic acid, whether composed of phosphodiester or modified linkages, such as phosphotriester, phosphoramidate, siloxane, carbonate, carboxymethyl ester, acetamidate, carbamate, thioether, bridged phosphoramidate, bridged methylene phosphonate, bridged phosphoramidate, bridged phosphoramidate, bridged methylene phosphonate, phosphorothioate, methylphosphonate, phosphorodithioate, bridged phosphorothioate, or sultone linkages, and combinations of such linkages. The terms "nucleic acid" and "polynucleotide" also specifically include nucleic acids composed of bases other than the five biologically occurring bases (adenine, guanine, thymine, cytosine, and uracil).

[0077] Self-assembling ENP as a vaccine platform technology In some embodiments, compositions (e.g., nucleic acid compositions, populations of ENPs) are provided. In some embodiments, the compositions are vaccine compositions. In some embodiments, the compositions include nucleic acid compositions (e.g., mRNA vaccines, DNA vaccines, constructs) comprising a polynucleotide encoding a fusion protein, wherein the fusion protein comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD), and wherein multiple fusion proteins are capable of self-assembly into enveloped nanoparticles (ENPs) that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs. In some embodiments, ENP-producing cells are provided. In some embodiments, the ENP-producing cells comprise the nucleic acid compositions disclosed herein.

[0078] In some embodiments, a composition (e.g., a nucleic acid composition, a population of ENPs) is provided. In some embodiments, the composition comprises a nucleic acid composition (e.g., an mRNA vaccine, a DNA vaccine) comprising n polynucleotides each encoding an nth fusion protein. In some embodiments, n is from 2 to 500 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 128, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, The nth fusion protein may be an integer between 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, or any number or range between any two of these values. Each fusion protein may comprise an AP and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD). At least two of the nth fusion proteins may differ with respect to the AP (e.g., heterologous antigen, different AP). In some embodiments, some or all of the nth fusion proteins differ with respect to the AP (e.g., heterologous antigen, different AP) presented, such that the population of ENPs presents multiple different APs (heterologous antigens). Multiple fusion proteins can self-assemble into ENPs that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs.

[0079] In some embodiments, the fusion protein can be displayed on the surface of a cell expressing the fusion protein. In some embodiments, self-assembly of ENPs: does not require any exogenous nucleic acid other than the nucleic acid composition, does not require any exogenous components other than the fusion proteins, and / or requires only a single component (e.g., the fusion protein). In some embodiments, the cell is: a cell of a subject; an in vivo cell, an ex vivo cell, or an in situ cell; and / or an adherent or suspension cell.

[0080] In some embodiments, upon secretion from the subject's cells, the ENPs are capable of distribution within one or more tissues of the subject (e.g., adrenal tissue, appendix tissue, bladder tissue, bone, intestinal tissue, brain tissue, breast tissue, bronchus, coronary tissue, ear tissue, esophageal tissue, eye tissue, gallbladder tissue, reproductive tissue, heart tissue, hypothalamus tissue, kidney tissue, large intestine tissue, intestinal tissue, laryngeal tissue, liver tissue, lung tissue, lymph node, oral tissue, nasal tissue, pancreatic tissue, parathyroid tissue, pituitary tissue, prostate tissue, rectal tissue, salivary gland tissue, skeletal muscle tissue, skin tissue, small intestine tissue, spinal cord, spleen tissue, stomach tissue, thymus tissue, tracheal tissue, thyroid tissue, ureteral tissue, urethral tissue, soft and connective tissue, peritoneal tissue, vascular tissue, adipose tissue, or any combination thereof). In some embodiments, the ENPs engage multiple immune cells in the one or more tissues, thereby mimicking a natural infection.

[0081] In some embodiments, the composition comprises a population of enveloped nanoparticles (ENPs), each of the ENPs comprising a plurality of fusion proteins, each comprising an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD). The ENPs may be derived from expression of a nucleic acid composition provided herein. At least two of the fusion proteins differ from each other with respect to the AP, and wherein the population of ENPs thereby displays a plurality of different APs (e.g., heterologous antigens).

[0082] The ENP may comprise a lipid bilayer (e.g., a lipid bilayer derived from the cell that secreted the ENP). In some embodiments, the ERD recruits one or more ESCRT proteins to the cytoplasmic tail of the fusion protein. In some embodiments, recruitment of ESCRT proteins via the ERD induces self-assembly and budding of ENPs. The cytoplasmic portion of the fusion protein comprises the ERD. The cytoplasmic tail of the fusion protein comprises the ERD. In some embodiments, the ERD interacts with the ESCRT proteins TSG101, NEDD4, and / or ALIX.

[0083] The ERD may comprise or be derived from a non-human protein, optionally a non-mammalian protein, further optionally a chicken protein, a mouse protein, a lizard protein, a reptile protein, a hamster protein, or a goldfish protein. The ERD may comprise or be derived from the ESCRT and ALIX binding region (EABR) of the human CEP55 protein, optionally residues 170 to 213. The ERD may comprise or be derived from syntenin-1, rat galectin-3 (rGalectin-3), Hrs, and / or CD2AP. The ERD may comprise or be derived from a viral protein, optionally a fragment of a viral protein, further optionally a retrovirus protein, a herpes simplex virus protein, a vaccinia virus protein, a hepadnavirus protein, a togavirus protein, a flavivirus protein, an arenavirus protein, a coronavirus protein, an orthomyxovirus protein, a paramyxovirus protein, a bunyavirus protein, a bornavirus protein, a rhabdovirus protein, or a filovirus protein, optionally a Gag protein, further optionally a Gag protein from EIAV, HTLV-1, MLV, or MPMV, optionally a Gag protein from EIAV p9 and / or HIV-1 p6. The ERD may comprise or be derived from an Ebola protein, optionally EBOV VP40.The ERD has at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, or any value or range between any two of these values, may include amino acid sequences that are identical. Tables 1 and 2 show non-limiting exemplary ERDs provided in this application.

[0084] In some embodiments, the nucleic acid composition does not comprise a polynucleotide encoding SpyTag or lentiviral Gag, hi some embodiments, the ENP does not comprise SpyTag or lentiviral Gag.

[0085] The fusion protein may comprise an endocytosis-preventing motif (EPM) of the fusion protein. In some embodiments, the EPM: tethers the fusion protein to the cytoskeleton, thereby preventing localization to coated pits and endocytosis; enhances ENP assembly, ENP production, and / or ENP secretion; and / or prevents endocytosis of the fusion protein, thereby increasing the time the fusion protein remains in the plasma membrane and interacts with ESCRT proteins. In some embodiments, the endocytosis-preventing motif (EPM) disclosed herein is used to generate a fusion protein with a T-cell receptor (TCR) or chimeric antigen receptor (CAR), which, in some embodiments, may enhance the activity and / or efficacy of T-cells and / or CAR-T-cells against a disease or disorder (e.g., cancer, infectious disease), optionally by at least about 1.1-fold. In some embodiments, an EPM-TCR fusion protein is provided, where the EPM is fused to a TCR. In some embodiments, an EPM-CAR fusion protein is provided, where the EPM is fused to a CAR. In some embodiments, without being bound by any particular theory, a TCR or CAR fused to an EPM remains on the T-cell surface for a longer period of time (e.g., at least about 1.1- or longer), and in some embodiments, a TCR or CAR fused to an EPM may interact more effectively with target antigens on cancer cells or infected cells, resulting in more effective killing of those cells. In some embodiments, nucleic acid compositions encoding one or more EPM-TCR fusion proteins and / or one or more EPM-CAR fusion proteins are provided. In some embodiments, cells (e.g., T-cells and / or CAR-T-cells) comprising one or more EPM-TCR fusion proteins and / or one or more EPM-CAR fusion proteins are provided.In some embodiments, methods are provided for treating a disease or disorder (e.g., cancer, infectious disease) comprising administering to a subject an effective amount of the nucleic acid compositions and / or cells (e.g., nucleic acid compositions encoding one or more EPM-TCR fusion proteins and / or one or more EPM-CAR fusion proteins, T-cells and / or CAR-T-cells comprising one or more EPM-TCR fusion proteins and / or one or more EPM-CAR fusion proteins).

[0086] the EPM reduces the abundance and / or density of the fusion protein on and / or in the ENP by at least about 2-fold (e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or a number or range between any of these values) compared to an ENP comprising the fusion protein without the EPM; and / or the number of ENPs secreted by the cells may be increased by at least about 2-fold (e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or a number or range between any of these values) compared to cells expressing the fusion protein without the EPM.

[0087] The EPM may comprise or be derived from a portion of the murine low-affinity gamma Fc region receptor II isoform FcRII-B1. The EPM may comprise an amino acid sequence that is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, or a number or range between any two of these values ​​identical to SEQ ID NO: 21.

[0088] The fusion protein may comprise one or more linkers, which may comprise one or more flexible amino acid residues, optionally about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, or a number or range between any two of these values, and further optionally, the flexible amino acid residues comprise glycine, serine, or a combination thereof. The one or more linkers may be a glycine-serine (GS) linker, optionally 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40 amino acids in length, or a number or range between any two of these values. The one or more linkers may be located between the ERD and AP, between the ERD and EPM, between the ERD and TD, between the EPM and TD, between the AP and EPM, and / or between the AP and TD.

[0089] The AP presented on the ENP described herein may be displayed on its surface. Alternatively, the AP presented on the ENP described herein may be partially encapsulated or embedded so that at least the immunogenic portion of the AP is exposed and accessible to host cell receptors to induce an immune response. The AP, or a portion thereof, may be displayed within the ENP and / or on the surface of the ENP. The APs may be from about 1 to about 10,000 (e.g., 1, 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, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 6000, The amino acid sequence may be 7000, 8000, 9000, 10000, or any number or range between any of these values.

[0090] The AP may comprise or be derived from an antigenic protein associated with a disease or disorder, optionally an immunogenic variant and / or immunogenic fragment of the antigenic protein. The AP may comprise or be derived from at least a portion of an antigenic protein. The AP may comprise or be derived from a conserved portion of the antigenic protein. The AP may be present on and / or in the ENP in its native membrane-bound conformation. The AP may comprise at least about 5 percent (e.g., 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%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, The AP may comprise or be derived from a soluble protein (e.g., 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, or a number or range between any two of these values). The AP may comprise a membrane protein (e.g., a multi-spanning transmembrane protein). In some embodiments, the AP is not configured to be a soluble protein. In some embodiments, the AP does not comprise one or more mutations configured to enhance its solubility and / or stability.

[0091] Thus, the AP may contain amino acid substitutions compared to the antigenic proteins disclosed herein. Any amino acid substitution is permissible as long as the immunogenic activity of the protein is not significantly altered (e.g., up to a 10%, 20%, 30%, 40%, or 50% reduction compared to the coronavirus protein antigens disclosed herein) and the variant retains the desired activity. Preferred variants typically contain substitutions of one or more amino acids with their functional equivalents.

[0092] In some embodiments, the AP does not contain a transmembrane domain and / or is a soluble protein, and wherein the fusion protein comprises a transmembrane domain (TD). The transmembrane domain may comprise or be derived from a non-human transmembrane protein (e.g., a non-mammalian transmembrane protein). The TD may comprise or be derived from a natural protein, a recombinant protein, and / or a synthetic protein (e.g., a synthetic protein comprising primarily hydrophobic residues).

[0093] The compositions described herein (e.g., nucleic acid compositions, populations of ENPs) may be prepared using any standard molecular biology procedure known to those of skill in the art, as well as the protocols exemplified herein (see, e.g., the Examples).

[0094] The nucleic acid composition may be produced using recombinant DNA techniques well known in the art. For example, ENP may be produced using an expression vector containing a nucleic acid molecule encoding the fusion protein described herein. The nucleic acid molecule may be operably linked to appropriate regulatory elements (e.g., but not limited to, a promoter, an enhancer, a transcription start site, a stop site, and a translation start site). The vector may contain one or more selectable marker genes, such as genes providing ampicillin resistance or kanamycin resistance. Methods for constructing nucleic acid constructs are well known. See, for example, Molecular Cloning: a Laboratory Manual, 3rd Edition, Sambrook et al. 2001 Cold Spring Harbor Laboratory Press, and Current Protocols in Molecular Biology, Ausubel et al. eds., John Wiley & Sons, 1994. In vitro transcription of RNA and / or cDNA encoding the polynucleotides described herein may be performed using an in vitro transcription (IVT) system. In vitro transcription of RNA is known in the art and is described in WO 2014 / 152027, which is incorporated herein by reference in its entirety. In some embodiments, the RNA of the present disclosure is prepared according to any one or more of the methods described in WO 2018 / 053209, US 2021 / 0251898, and WO 2019 / 036682, each of which is incorporated herein by reference. ENPs may be produced (and isolated) from cells containing the nucleic acid compositions provided herein.For example, ENPs may be derived from a cell culture transiently transfected with the nucleic acid composition, which may optionally be derived by ultracentrifugation and / or size-exclusion chromatography, further optionally by ultracentrifugation on a 20% sucrose cushion, and which may optionally be transfected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, electrical nuclear transport, chemical transduction, electrotransduction, lipofectamine-mediated transfection, Effectene-mediated transfection, lipid nanoparticle (LNP)-mediated transfection, or any combination thereof. The systems, methods, compositions, and kits provided in this application may, in some embodiments, be used in conjunction with the systems, methods, compositions, and kits described in International Publication No. WO 2022103891A1, PCT application entitled "Multivalent carriers and related vaccine compositions," filed November 10, 2021, the contents of which are incorporated by reference in their entirety into this application.

[0095] pathogenic antigen The AP may comprise or may be derived from a full-length surface protein of an infectious agent. The disease or disorder may be an infectious disease or disorder caused by an infectious agent, wherein the AP may comprise or may be derived from an antigenic protein of the infectious agent, and wherein the antigenic protein of the infectious agent may be a pathogenic antigen. In some embodiments, the virulence antigen is selected from the group comprising: outer membrane protein A OmpA, biofilm-associated protein Bap, transport protein MucK (Acinetobacter baumannii, Acinetobacter infection); variable surface glycoprotein VSG, microtubule-associated protein MAPP15, trans-sialidase TSA (Trypanosoma brucei, sleeping sickness (African trypanosomiasis)); HIV p24 antigen, HIV envelope proteins (Gp120, Gp41, Gp160), polyprotein GAG, negative factor protein Nef, trans-transcriptional activator Tat (HIV (human immunodeficiency virus), AIDS (acquired immune deficiency syndrome)); galactose-inhibitory adhesion protein GIAP, 29 kDa antigen Eh29, Gal / GaINAc lectin, protein CRT, 125 kDa Immunodominant antigen, protein M17, adhesin ADH112, protein STIRP (Entamoeba histolytica, Amoebiasis); major surface proteins 1-5 (MSP1a, MSP1b, MSP2, MSP3, MSP4, MSP5), type IV secretion system proteins (VirB2, VirB7, VirB11, VirD4) (Anaplasma genus, Anaplasmosis); protective antigen PA, edema factor EF, lethal factor LF, S-layer homology protein SLH (Bacillus anthracis, Anthrax);acranolysin, phospholipase D, collagen-binding protein CbpA (Arcanobacterium haemolyticum, Arcanobacterium haemolyticum infection); nucleocapsid protein NP, glycoprotein precursor GPC, glycoprotein GP1, glycoprotein GP2 (Junin virus, Argentine hemorrhagic fever); chitin-protein layer protein, 14 kDa surface antigen A14, major sperm protein MSP, MSP polymerization-organizing protein MPOP, MSP fiber protein 2 MFP2, MSP polymerization-activating kinase MPAK, ABA-1-like protein ALB, protein ABA-1, cuticulin CUT-1 (Ascaris lumbricoides, Ascariasis); 41 kDa allergen Asp v13, allergen Asp f3, major conidial surface protein; rodlet A, protease; Pep1p, GPI-anchored protein; Gel1p, GPI-anchored protein; Crap (Aspergillus genus, Aspergillosis); family VP26 protein, VP29 protein (Astroviridae, Astrovirus infection); Rhoptry-associated protein 1 (RAP-1), merozoite surface antigens (MSA-1, MSA-2 (a1, a2, c), 12D3, 1105, 21134, P29), variant erythrocyte surface antigen (VESA1); apical membrane antigen 1 (AMA-1) (Babesia genus, Babesiosis);Hemolysin, enterotoxin C, PX01-51, glycolate oxidase, ABC-transporter, penicillin-binding protein, zinc transporter family protein, pseudouridine synthase Rsu, plasmid replication protein RepX, oligoendopeptidase F, prophage membrane protein, protein HemK, flagellar antigen H, 28.5-kDa cell surface antigen (Bacillus cereus, B. cereus infection); large T antigen LT, small T antigen, capsid protein VP1, capsid protein VP2 (BK virus, BK virus infection); 29-kDa protein, caspase-3-like antigen, glycoprotein (Blastocystis hominis, B. hominis infection); yeast surface adhesin WI-1 (Blastomyces dermatitidis, Blastomycosis); nucleoprotein N, polymerase L, matrix protein Z, glycoprotein GP (Machupo virus, Bolivian hemorrhagic fever); outer surface protein A OspA, outer surface protein OspB, outer surface protein OspC, decorin-binding protein A DbpA, decorin-binding protein B DbpB, flagellar filament 41 kDa core protein Fla, basement membrane protein A precursor BmpA (immunodominant antigen P39), outer surface 22 kDa lipoprotein precursor (antigen IPLA7), variable surface lipoprotein vlsE (Borrelia genus, Borrelia infection); botulinum neurotoxin BoNT / A1, BoNT / A2, BoNT / A3, BoNT / B, BoNT / C, BoNT / D, BoNT / E, BoNT / F, BoNT / G, recombinant botulinum toxin F Hc domain FHc (Clostridium botulinum, botulism (and infant botulism)); nucleocapsid, glycoprotein precursor (Sabia virus, Brazilian hemorrhagic fever);Copper / zinc superoxide dismutase SodC, bacterioferritin Bfr, ​​50S ribosomal protein RplL, OmpA-like transmembrane domain-containing protein Omp31, immunogenic 39-kDa protein M5 p39, zinc ABC transporter periplasmic zinc-binding protein znuA, periplasmic immunogenic protein Bp26, 30S ribosomal protein S12 RpsL, glyceraldehyde-3-phosphate dehydrogenase Gap, 25 kDa outer membrane immunogenic protein precursor Omp25, invasion protein B laIB, trigger factor Tig, molecular chaperone DnaK, putative peptidyl-prolyl cis-trans isomerase SurA, lipoprotein Omp19, outer membrane protein MotY Omp16, conserved outer membrane protein D15, malate dehydrogenase Mdh, component of type-IV secretion system (TOSS) VirJ, lipoprotein of unknown function BAB1_0187 (Brucella genus, Brucellosis); members of the ABC transporter family (LoIC, OppA, and PotF), putative lipoprotein release system transmembrane protein LoIC / E, flagellin FliC, Burkholderia intracellular motility A BimA, bacterial elongation factor-Tu EF-Tu, 17 kDa OmpA-like protein, boaA coding protein, boaB coding protein (Burkholderia cepacia and other Burkholderia species, Burkholderia infection); mycolyltransferase Ag85A, heat shock protein Hsp65, protein TB10.4, 19 kDa antigen, protein PstS3, heat shock protein Hsp70 (Mycobacterium ulcerans, Buruli ulcer);Norovirus major and minor virus capsid proteins VP1 and VP2, genome polyprotein, Sapovirus capsid protein VP1, protein Vp3, genome polyprotein (family Caliciviridae, calicivirus infections (norovirus and sapovirus)); major envelope protein PorA, flagellin FlaA, surface antigen CjaA, fibronectin-binding protein CadF, aspartate / glutamate-binding ABC transporter protein PeblA, protein FspAl, protein FspA2 (Campylobacter genus, campylobacteriosis); glycolytic enzyme enolase, secreted aspartyl protease SAP1-10, glycophosphatidylinositol (GPI)-linked cell wall protein, protein Hyrl, complement receptor 3-related protein CR3-RP, adhesin Als3p, heat shock protein 90 kDa hsp90, cell surface hydrophobic protein CSH (typically Candida albicans and other Candida species, candidiasis); 17-kDa antigen, protein P26, trimeric autotransporter adhesins TAAs, Bartonella adhesin A BadA, variably expressed outer-membrane proteins Vomps, protein Pap3, protein HbpA, envelope-associated protease HtrA, protein OMP89, protein GroEL, protein LaIB, protein OMP43, dihydrolipoamide succinyltransferase SucB (Bartonella henselae, cat-scratch disease);Amastigotes surface protein-2, amastigotes-specific surface protein; SSP4, cruzipain, trans-sialidase; TS, trypomastigotes surface glycoprotein; TSA-1, complement regulatory protein; CRP-10, protein; G4, protein; G2, accessory flagellar rod protein; PAR2, accessory flagellar rod component; Part, mucin-binding surface protein; MPSP (Trypanosoma cruzi, Chagas Disease (American trypanosomiasis)); envelope glycoproteins (gB, gC, gE, gH, gI, gK, gL) (Varicella zoster virus (VZV), Chickenpox); major outer membrane protein; MOMP, putative outer membrane protein; PMPC, outer membrane complex protein B; OmcB, heat shock protein; Hsp60; HSP10, protein IncA, protein from type III secretion system, ribonucleotide reductase small chain protein NrdB, plasmid protein Pgp3, chlamydial exoprotein N CopN, antigen CT521, antigen CT425, antigen CT043, antigen TC0052, antigen TC0189, antigen TC0582, antigen TC0660, antigen TC0726, antigen TC0816, antigen TC0828 (Chlamydia trachomatis, Chlamydiosis);Low calcium response protein E LCrE, chlamydial outer protein N CopN, serine / threonine-protein kinase PknD, acyl-carrier protein S-malonyltransferase FabD, single-stranded DNA-binding protein Ssb, major outer membrane protein MOMP, outer membrane protein 2 Omp2, polymorphic membrane protein family (Pmp1, Pmp2, Pmp3, Pmp4, Pmp5, Pmp6, Pmp7, Pmp8, Pmp9, Pmp10, Pmp11, Pmp12, Pmp13, Pmp14, Pmp15, Pmp16, Pmp17, Pmp18, Pmp19, Pmp20, Pmp21) (Chlamydophila pneumoniae, Chlamydophila pneumoniae infection); cholera toxin B CTB, toxin coregulator pyrin A TcpA, toxin co-regulated pilus biosynthesis protein F; TcpF, toxin co-regulated pilus biosynthesis protein F; TcpF, cholera enterotoxin subunit A; cholera enterotoxin subunit B; heat-stable enterotoxin; ST, mannose-sensitive hemagglutinin; MSHA, outer membrane protein U; ​​ompU, porin B protein; polymorphic membrane protein D (Vibrio cholerae, cholera); propionyl-CoA carboxylase; PCC, 14-3-3 protein; prohibitin, cysteine ​​protease; glutathione transferase; gelsolin; cathepsin L protease; CatL, tegument protein 20.8 kDa; TP20.8, tegument protein 31.8 kDa. TP31.8, lysophosphatidic acid phosphatase LPAP, (Clonorchis sinensis, Clonorchiasis);Surface layer proteins SLPs, glutamate dehydrogenase antigen GDH, toxin A, toxin B, cysteine ​​protease Cwp84, cysteine ​​protease Cwp13, cysteine ​​protease Cwp19, cell wall protein CwpV, flagellar protein FliC, flagellar protein FliD (Clostridium difficile, C. difficile infection); rhinoviruses: capsid proteins VP1, VP2, VP3, VP4; coronaviruses: spike protein S, envelope protein E, membrane protein M, nucleocapsid protein N (usually rhinoviruses and coronaviruses, common cold (acute viral nasopharyngitis; acute coryza)); prion protein Prp (CJD prion, Creutzfeldt-Jakob disease (CJD)); Envelope protein Gc, envelope protein Gn, nucleocapsid protein (Crimean-Congo hemorrhagic fever virus, Crimean-Congo hemorrhagic fever (CCHF)); virulence-associated DEAD-box RNA helicase VAD1, galactoxylomannan-protein GaIXM, glucuronoxylomannan GXM, mannoprotein MP (Cryptococcus neoformans, cryptococcosis); acidic ribosomal protein P2 CpP2, mucin antigens Muc1, Muc2, Muc3, Muc4, Muc5, Muc6, Muc7, surface adhesion protein CP20, surface adhesion protein CP23, surface protein CP12, surface protein CP21, surface protein CP40, surface protein CP60, surface protein CP15, surface-associated glycopeptide gp40, surface-associated glycopeptide gp15, oocyst wall protein AB, profilin PRF, apyrase (Cryptosporidium genus, Cryptosporidiosis); fatty acid and retinol binding protein-1 FAR-1, tissue inhibitor of metalloproteinase (TIMP) ACEY-1, cysteine ​​protease ACCP-1, surface antigen Ac-16, secreted protein 2 ASP-2, metalloproteinase 1 MTP-1, aspartyl protease inhibitor API-1, surface-associated antigen SAA-1, adult-specific secreted factor Xa serine protease inhibitor anticoagulant AP, cathepsin D-like aspartic protease ARR-1 (usually Brazilian hookworm (Ancylostoma braziliense); multiple other parasites, Cutaneous larva migrans (CLM));Cathepsin L-like protease, 53 / 25-kDa antigen, 8 kDa family member, cysticercus protein with a marginal trypsin-like activity TsAg5, oncocysticercosis protein TSOL18, oncocysticercosis protein TSOL45-1A, lactate dehydrogenase A LDHA, lactate dehydrogenase B LDHB (Taenia solium, neurocysticercosis); pp65 antigen, membrane protein pp15, capsid-proximal tegument protein pp150, protein M45, DNA polymerase UL54, helicase UL105, glycoprotein gM, glycoprotein gN, glycoprotein H, glycoprotein B gB, protein UL83, protein UL94, protein UL99 (cytomegalovirus (CMV), cytomegalovirus infection); capsid protein C, premembrane protein prM, membrane protein M, envelope protein E (domain I, domain II, domain II), protein NS1, protein NS2A, protein NS2B, protein NS3, protein NS4A, protein 2K, protein NS4B, protein NS5 (dengue virus (DEN-1, DEN-2, DEN-3 and DEN-4) - flavivirus, dengue fever); 39 kDa protein (Dientamoeba fragilis, dientamoebiasis); diphtheria toxin precursor Tox, diphtheria toxin DT, pilin-specific sortase SrtA, shaft pilin protein SpaA, tip pilin protein SpaC, minor pilin protein SpaB, surface-associated protein DIP1281 (Corynebacterium diphtheriae, Diphtheria);Glycoprotein GP, ​​nucleoprotein NP, minor matrix protein VP24, major matrix protein VP40, transcription activator VP30, polymerase cofactor VP35, RNA polymerase L (Ebola virus (EBOV)), Ebola hemorrhagic fever); prion protein (vCJD prion, variant Creutzfeldt-Jakob disease (vCJD, nvCJD)); UvrABC system protein B, protein Flp1, protein Flp2, protein Flp3, protein TadA, hemoglobin receptor HgbA, outer membrane protein TdhA, protein CpsRA, regulator CpxR, protein SapA, 18 kDa antigen, outer membrane protein NcaA, protein LspA, protein LspA1, protein LspA2, protein LspB, outer membrane component DsrA, lectin DItA, lipoprotein Hip, major outer membrane protein; OMP, outer membrane protein OmpA2 (Haemophilus ducreyi, Chancroid); aspartyl protease 1 Pep1; phospholipase B PLB; alpha-mannosidase 1 AMN1; glucanosyltransferase GEL1; urease URE; peroxisomal matrix protein Pmp1; proline-rich antigen Pra, human T-cell reactive protein TcrP (Coccidioides immitis and Coccidioides posadasii, Coccidioidomycosis);Allergen Tri r 2, heat shock protein 60 Hsp60, fungal actin Act, antigen Tri r2, antigen Tri r4, antigen Tri t1, protein IV, glycerol-3-phosphate dehydrogenase Gpd1, osmoreceptor HwSho1A, osmoreceptor HwSho1B, histidine kinase HwHhk7B, allergen Mala s 1, allergen Mala s 11, thioredoxin Trx Mala s 13, allergen Mala f, allergen Mala s (usually Trichophyton spp., Epidermophyton spp., Malassezia spp., Hortaea werneckii, dermatophytosis); protein EG95, protein EG10, protein EG18, protein EgA31, protein EM18, antigen EPC1, antigen B, antigen 5, protein P29, protein 14-3-3, 8-kDa protein, myophilin, heat shock protein 20 HSP20, glycoprotein GP-89, fatty acid binding protein FAPB (Echinococcus genus, Echinococcosis); major surface protein 2 MSP2, major surface protein 4 MSP4, MSP variant SGV1, MSP variant SGV2, outer membrane protein OMP, outer membrane protein 19 OMP-19, major antigenic protein MAP1, major antigenic protein MAP1-2, major antigenic protein MAP1B, major antigenic protein MAP1-3, Erum2510 coding protein, protein GroEL, protein GroES, 30-kDa major outer membrane protein, GE 100-kDa protein, GE 130-kDa protein, GE 160-kDa protein (Ehrlichia genus, Ehrlichiosis);Secretory antigen SagA, sagA-like proteins SalA and SaIB, collagen adhesin Scm, surface proteins Fms1 (EbpA(fm), Fms5 (EbpB(fm), Fms9 (EpbC(fm) and Fms10), protein EbpC(fm), 96 kDa immune defense glycoprotein G1 (Enterococcus genus, Enterococcus infection); genome polyprotein, polymerase 3D, viral capsid protein VP1, viral capsid protein VP2, viral capsid protein VP3, viral capsid protein VP4, protease 2A, protease 3C (Enterovirus genus, Enterovirus infection); outer membrane protein OM, 60 kDa outer membrane protein, cell surface antigen OmpA, cell surface antigen OmpB (sca5), 134-kDa outer membrane protein, 31-kDa outer membrane protein, 29.5-kDa outer membrane protein, cell surface protein SCA4, cell surface protein Adr1 (RP827), cell surface protein Adr2 (RP828), cell surface protein SCA1, invasion protein invA, cell division protein fts, secreted proteins secO family, virulence proteins virB, tlyA, and tlyC, parvulin-like protein Plp, preprotein translocase SecA, 120-kDa surface protein antigen SPA, 138-kD complex antigen, major 100-kD protein (protein I), cytoplasmic protein D, protective surface protein antigen SPA (Rickettsia prowazekii, Epidemic typhus);Epstein-Barr nuclear antigens (EBNA-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, EBNA-leader protein (EBNA-LP)), latent membrane proteins (LMP-1, LMP-2A, LMP-2B), early antigen EBV-EA, membrane antigen EBV-MA, viral capsid antigen EBV-VCA, alkaline nuclease EBV-AN, glycoproteins glycoprotein gp350, glycoprotein gp110, glycoprotein gp42, glycoprotein gHgL, glycoprotein gB (Epstein-Barr Virus (EBV), Epstein-Barr Virus Infectious Mononucleosis); capsid protein VP2, capsid protein VP1, major protein NS1 (Parvovirus B19, Erythema infectiosum (fifth disease)); pp65 antigen, glycoprotein 105, major capsid protein, envelope glycoprotein H, protein U51 (Human herpesvirus 6 (HHV-6) and Human herpesvirus 7 (HHV-7), Exanthem subitum);Thioredoxin-glutathione reductase TGR, cathepsins L1 and L2, Kunitz-type protein KTM, leucine aminopeptidase LAP, cysteine ​​protease Fast, saposin-like protein-2 SAP-2, thioredoxin peroxidase TPx, Prx-1, Prx-2, cathepsin I cysteine ​​protease CL3, cathepsin L protease CL1, phosphoglycerate kinase PGK, 27-kDa secretory protein, 60 kDa protein HSP35alpha, glutathione transferase GST, 28.5 kDa tegumental antigen 28.5 kDa TA, cathepsin B3 protease CatB3, type I cystatin stefin-1, cathepsin L5, cathepsin L1g, and cathepsin B, fatty acid-binding protein FABP, leucine aminopeptidase LAP (Fasciola hepatica and Fasciola gigantica, Fasciolosis); prion protein (FFI, Fatal familial insomnia (FFI));Venom allergen homolog-like protein VAL-1, abundant larval transcript ALT-1, abundant larval transcript ALT-2, thioredoxin peroxidase TPX, hornet allergen homolog VAH, thiordoxin peroxidase 2 TPX-2, antigenic protein SXP (peptides N, N1, N2, and N3), activation-associated protein-1 ASP-1, thioredoxin TRX, transglutaminase BmTGA, glutathione-S-transferase GST, myosin, hornet allergen homolog VAH, 175 kDa collagenase, glyceraldehyde-3-phosphate dehydrogenase GAPDH, cuticle collagen Col-4, secreted larval acidic proteins SLAPs, chitinase CHI-1, maltose-binding protein MBP, glycolytic enzyme fructose-1,6-bisphosphate aldolase Fba, tropomyosin TMY-1, nematode-specific gene product OvB20, onchocystatin CPI-2, Cox-2 (Filarioidea superfamily, Filariasis); phospholipase C PLC, heat-labile enterotoxin B, iota toxin component Ib, protein CPE1281 pyruvate ferredoxin oxidoreductase, elongation factor G EF-G, perfringolysin 0 Pfo, glyceraldehyde-3-phosphate dehydrogenase GapC, fructose-bisphosphate aldolase Alf2, Clostridium perfringens enterotoxin CPE, alpha toxin AT, alpha toxoid ATd, epsilon toxoid ETd, protein HP, large cytotoxin TpeL, endo-beta-N-acetylglucosaminidase Naglu, phosphoglyceromutase Pgm (Clostridium perfringens, food poisoning caused by Clostridium perfringens);Leukotoxin IktA, adhesion FadA, outer membrane protein RadD, high molecular weight arginine-binding protein (Fusobacterium genus, Fusobacterium infection); phospholipase C PLC, heat-labile enterotoxin B, iota toxin component Ib, protein CPE1281, pyruvate ferredoxin oxidoreductase, elongation factor G; EF-G, perfringolysin 0 Pfo; Glyceraldehyde-3-phosphate dehydrogenase GapC, fructose-bisphosphate aldolase Alf2, Clostridium perfringens enterotoxin CPE, alpha-toxin AT, alpha-toxoid ATd, epsilon-toxoid ETd, protein HP, large cell toxin TpeL, endo-beta-N-acetylglucosaminidase Naglu, phosphoglycerin mutase Pgm (usually Clostridium perfringens; other Clostridium species, gas gangrene (clostridial myonecrosis)); lipase A, lipase B, peroxidase Dec1 (Geotrichum candidum, geotrichosis); prion protein (GSS) Prion, Gerstmann-Straussler-Scheinker syndrome (GSS); cyst wall proteins CWP1, CWP2, CWP3; variant surface proteins VSP, VSP1, VSP2, VSP3, VSP4, VSP5, VSP6; 56 kDa antigen; pyruvate ferredoxin oxidoreductase PFOR, alcohol dehydrogenase E ADHE, alpha-giardin, alpha8-giardin, alpha1-giardin, beta-giardin; cysteine ​​protease; glutathione S-transferase GST, arginine deiminase ADI, fructose-1,6-bisphosphate aldolase FBA, Giardia trophozoite antigen GTA (GTA1, GTA2), ornithine carboxyl transferase OCT, striated fiber-asseblin-like protein SALP, uridine phosphoryl-like protein UPL, alpha-tubulin, beta-tubulin (Giardiaintestinalis, Giardiasis); ABC transporter family members (LoIC, OppA, and PotF), putative lipoprotein release system transmembrane protein LoIC / E, flagellin FliC, Burkholderia intracellular motility A BimA, bacterial elongation factor-Tu EF-Tu, 17 kDa OmpA-like protein, boaA coding protein (Burkholderia mallei, Glanders); cyclophilin CyP, 24 kDa third stage larval protein GS24, excretory-secretory products ESPs (40, 80, 120, and 208 kDa) (Gnathostoma spinigerum and Gnathostoma hispidum, Gnathostomiasis); Pilin protein, minor pilin-related subunit pilC, major pilin subunit and variant pilE, pilS, phase variant protein porA, porin B PorB, protein TraD, Neisseria outer membrane antigen H.8, 70 kDa antigen, major outer membrane protein PI, outer membrane proteins PIA and PIB, W antigen, surface protein A NspA, transferrin-binding protein TbpA, transferrin-binding protein TbpB PBP2, mtrR coding protein, ponA coding protein, membrane permease FbpBC, FbpABC protein system, LbpAB protein, outer membrane protein Opa, outer membrane transporter FetA, iron repressible regulator MpeR (Neisseria gonorrhoeae, Gonorrhea); outer membrane protein A OmpA, outer membrane protein C OmpC, outer membrane protein K17 OmpK17 (Klebsiella granulomatis, Granuloma inguinale (Donovanosis)); fibronectin-binding proteinSfb, fibronectin / fibrinogen-binding protein FBP54, fibronectin-binding protein FbaA, M protein type 1 Emml, M protein type 6 Emm6, immunoglobulin-binding protein 35 Sib35, surface protein R28 Spr28, superoxide dismutase SOD, C5a peptidase ScpA, antigen I / II AgI / II, adhesin AspA, G-related alpha2-macroglobulin-binding protein GRAB, surface fibrous protein M5 (Streptococcus pyogenes, Group A streptococcal infection); C protein β antigen, arginine deiminase protein, adhesin BibA, 105 kDA protein BPS, surface antigen c, surface antigen R, surface antigen X, trypsin-resistant protein R1, trypsin-resistant protein R3, trypsin-resistant protein R4, surface immunogenic protein Sip, surface protein Rib, leucine-rich repeat protein LrrG, serine-rich repeat protein Srr-2, C protein alpha-antigen Bca, beta antigen Bag, surface antigen epsilon, alpha-like protein ALP1, alpha-like protein ALP5 surface antigen delta, alpha-like protein ALP2, alpha-like protein ALP3, alpha-like protein ALP4, C beta protein Bac (Streptococcus agalactiae, Group B streptococcal infection); transferrin-binding protein 2 Tbp2, phosphatase P4, outer membrane protein P6, peptidoglycan-associated lipoprotein Pal, protein D, protein E, adhesion and invasion protein Hap, outer membrane protein 26 Omp26, outer membrane protein P5 (fimbrin), outer membrane protein D15, outer membrane protein OmpP2, 5′-nucleotidase NucA, outer membrane protein P1, outer membrane protein P2, outer membrane lipoprotein Pcp, lipoproteinE, outer membrane protein P4, fucokine kinase FucK, [Cu,Zn]-superoxide dismutase SodC, protease HtrA, protein O145, alpha-galactosylceramide (Haemophilus influenzae, Haemophilus influenzae infection); polymerase 3D, viral capsid protein VP1, viral capsid protein VP2, viral capsid protein VP3, viral capsid protein VP4, protease 2A, protease 3C (enteroviruses, mainly Coxsackie A virus and enterovirus 71 (EV71), hand, foot, and mouth disease (HFMD)); RNA polymerase L, protein L, glycoprotein Gn, glycoprotein Gc, nucleocapsid protein 5, envelope glycoprotein G1, nucleoprotein NP, protein N, polyprotein M (Sin Nombre virus, Hantavirus, Hantavirus Pulmonary Syndrome (HPS)); heat shock protein HspA, heat shock protein HspB, citrate synthase GItA, protein UreB, heat shock protein Hsp60, neutrophil-activating protein NAP, catalase KatA, vacuolating cytotoxin VacA, urease alpha UreA, urease beta Ureb, protein Cpn10, protein groES, heat shock protein Hsp10, protein MopB, cytotoxicity-associated 10 kDa protein CAG, 36 kDa antigen, beta-lactamase HcpA, beta-lactamase HcpB (Helicobacter pylori, Helicobacter pylori infection) infection); integral membrane protein, aggregation-prone proteinprotein), O-antigen, toxin-antigen Stx2B, toxin-antigen Stx1B, adhesion-antigen fragment Int28, protein EspA, protein EspB, intimin, protein Tir, protein IntC300, protein Eae (Escherichia coli O157:H7, O111, and O104:H4, hemolytic-uremic syndrome (HUS)); RNA polymerase L, protein L, glycoprotein Gn, glycoprotein Gc, nucleocapsid protein 5, envelope glycoprotein G1, nucleoprotein NP, protein N, polyprotein M (Bunyaviridae family, hemorrhagic fever with renal syndrome (HFRS)); glycoprotein G, matrix protein M, nucleoprotein N, fusion protein F, polymerase L, protein W, protein C, phosphoprotein p, non-structural protein V (Henipavirus (Hendra virus, Nipah virus), Henipavirus infection); polyprotein, glycoprotein Gp2, hepatitis A surface antigen HBAg, protein 2A, viral protein VP1, viral protein VP2, viral protein VP3, viral protein VP4, protein P1B, protein P2A, protein P3AB, protein P3D (hepatitis A virus, Hepatitis A); hepatitis B surface antigen HBsAg, hepatitis B core antigen HbcAg, polymerase, protein Hbx, preS2 middle surface protein, surface protein L, large S protein, viral protein VP1, viral protein VP2, viral protein VP3, viral protein VP4 (hepatitis B virus (HBV), Hepatitis B); envelope glycoprotein E1 gp32 gp35, envelope glycoprotein E2 NS1 gp68 gp70, capsid protein C, core protein Core, polyprotein, viral protein VP1, viral proteinVP2, viral protein VP3, viral protein VP4, antigen G, protein NS3, protein NSSA (hepatitis C virus, hepatitis C); viral protein VP1, viral protein VP2, viral protein VP3, viral protein VP4, large hepatitis delta antigen, small hepatitis delta antigen (hepatitis D virus, hepatitis D); viral protein VP1, viral protein VP2, viral protein VP3, viral protein VP4, capsid protein E2 (hepatitis E virus, hepatitis E); glycoprotein L UL1, uracil-DNA glycosylase UL2, protein UL3, protein UL4, DNA replication protein UL5, portal protein UL6, virion maturation protein UL7, DNA helicase UL8, origin-binding protein UL9, glycoprotein M UL10, protein UL11, alkaline exonuclease UL12, serine-threonine protein kinase; UL13, tegument protein; UL14, terminase; UL15, tegument protein; UL16, protein; UL17, capsid protein VP23; UL18, major capsid protein VP5; UL19, membrane protein; UL20, tegument protein; UL21, glycoprotein H (UL22), thymidine kinase; UL23, protein; UL24, protein; UL25, capsid protein; P40 (UL26, VP24, VP22A), glycoprotein B (UL27), ICP18.5 protein (UL28), major DNA-binding protein; ICP8 (UL29), DNA polymerase; UL30, nuclear matrix protein; UL31, envelope glycoprotein; UL32, protein; UL33, inner nuclear membrane protein; UL34, capsid protein. VP26 (UL35), large tegument protein UL36, capsid assembly protein UL37, VP19C protein (UL38), ribonucleotide reductase (large subunit) UL39, ribonucleotide reductase (small subunit) UL40, tegument protein / virion host shutoff (virionhost shutoff) VHS protein (UL41), DNA polymerase processivity factor UL42, membrane protein UL43, glycoprotein C (UL44), membrane protein UL45, tegument protein VP11 / 12 (UL46), tegument protein VP13 / 14 (UL47), virion maturation protein VP16 (UL48, alpha-TIF), envelope protein UL49, dUTP diphosphatase UL50, tegument protein UL51, DNA helicase / primase complex protein UL52, glycoprotein K (UL53), transcriptional regulatory protein 1E63 (ICP27, UL54), protein UL55, protein UL56, viral replication protein ICP22 (1E68, US1), protein U52, serine / threonine-protein kinase U53, glycoprotein G (U54), glycoprotein J (U55), glycoprotein D (U56), glycoprotein I (U57), glycoprotein E (U58), tegument protein U59, capsid / tegument protein US10, Vmw21 protein (US11), ICP47 protein (IE12, US12), major transcription activator ICP4 (1E175, RS1), E3 ubiquitin ligase ICPO (IE110), Latency-associated protein 1 LRP1, latency-associated protein 2 LRP2, neurovirulence factor RL1 (ICP34.5), latency-associated transcript LAT (Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), Herpes simplex); heat shock protein Hsp60, cell surface protein H1C, dipeptidyl peptidase type IV DppIV, M antigen, 70 kDa protein, 17 kDa histone-like protein (Histoplasma capsulatum, Histoplasmosis); fatty acid and retinol binding protein-1 FAR-1, tissue inhibitor of metalloproteinase TIMP (TMP), cysteine ​​protease ACEY-1, cysteine ​​protease ACCP-1, surface antigen Ac-16, secreted protein 2 ASP-2, metalloprotease 1; MTP-1, aspartyl protease inhibitor; API-1, surface-associated antigen; SAA-1, surface-associated antigen; SAA-2, adult-specific secretory factor Xa, serine protease inhibitor anticoagulant; AP, cathepsin D-like aspartic protease; ARR-1, 5-transferase; GST, aspartic protease; APR-1, acetylcholinesterase; AChE (Ancylostoma duodena le and Necator americanus, hookworm infection); NS1, NP1, VP1, VP2, and VP3 proteins (human bocavirus (HBoV), human bocavirus infection);Major surface protein 2 MSP2, major surface protein 4 MSP4, MSP variant SGV1, MSP variant SGV2, outer membrane protein OMP, outer membrane protein 19 OMP-19, major antigenic protein MAP1, major antigenic protein MAP1-2, major antigenic protein MAP1B, major antigenic protein MAP1-3, Erum2510 coding protein, protein GroEL, protein GroES, 30-kDA major outer membrane protein, GE 100-kDa protein, GE 130-kDa protein, GE 160-kDa protein (Ehrlichia ewingii; Human ewingii ehrlichiosis); major surface proteins 1-5 (MSP1a, MSP1b, MSP2, MSP3, MSP4, MSP5), type IV secretion system proteins VirB2, VirB7, VirB11, VirD4 (Anaplasma phagocytophilum, human granulocytic anaplasmosis (HGA)); protein NS1, small hydrophobic protein N52, SH protein, fusion protein F, glycoprotein G, matrix protein M, matrix protein M2-1, matrix protein M2-2, phosphoprotein P, nucleoprotein N, polymerase L (human metapneumovirus (hMPV), human metapneumovirus infection); major surface protein 2 MSP2, major surface protein 4 MSP4, MSP variants SGV1, MSP variant SGV2, outer membrane protein OMP, outer membrane protein 19 OMP-19, major antigenic protein MAP1, major antigenic protein MAP1-2, major antigenic protein MAP1B, major antigenic protein MAP1-3, coding protein Erum2510, protein GroEL, protein GroES, 30-kDA major outer membrane protein, GE 100-kDa protein, GE 130-kDa protein, GE 160-kDa protein (Ehrlichia chaffeensis, human monocytic ehrlichiosis); replication protein E1, regulatory protein E2, protein E3, protein E4, protein ES, protein E6, protein E7, protein E8, major capsid protein L1, minor capsid protein L2 (human papillomavirus (HPV), human papillomavirus (HPV) infection);Fusion protein F, hemagglutinin-neuraminidase HN, glycoprotein G, matrix protein M, phosphoprotein P, nucleoprotein N, polymerase L (human parainfluenza virus (HPIV), human parainfluenza virus infection); hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), M1 protein, M2 protein, NS1 protein, NS2 protein (NEP protein: nuclear export protein), PA protein, PB1 protein (polymerase basic 1 protein), PB1-F2 protein, and PB2 protein (Orthomyxoviridae family, influenza virus (influenza)); genome polyprotein, protein E, protein M, capsid protein C (Japanese encephalitis virus, Japanese encephalitis); RTX toxin, type IV pilus, major pilus subunit, PilA, regulatory transcription factor PilS and PilR, protein sigma 54, outer membrane protein (Kingella kingae, Kingella kingae infection); prion protein (Kuru prion, kuru); nucleoprotein N, polymerase L, matrix protein Z, glycoprotein GP (Lassa virus, Lassa fever); peptidoglycan-associated lipoprotein PAL, 60 kDa chaperonin Cpn60 (groEL, HspB), type IV pilin PilE, outer membrane protein MIP, major outer membrane protein MompS, zinc metalloprotease MSP (Legionella pneumophila, Legionnaires' disease, Pontiac fever);P4 nuclease, protein WD, ribonucleotide reductase M2, surface membrane glycoprotein Pg46, cysteine ​​protease CP, glucose-regulated protein 78 GRP-78, stage-specific S antigen-like protein A2, ATPase F1, beta-tubulin, heat shock protein 70 Hsp70, KMP-11, glycoprotein GP63, protein BT1, nucleoside hydrolase NH, cell surface protein B1, ribosomal protein P1-like protein P1, sterol 24-c-methyltransferase SMT, LACK protein, histone H1, SPB1 protein, thiol-specific antioxidant TSA, protein antigen STI1, signal peptidase SP, histone H2B, surface antigen PSA-2, cysteine ​​protease b Cpb (Leishmania genus, leishmaniasis); major membrane protein I, serine-rich antigen-45 kDa, 10 kDa chaperonin GroES, HSP kDa antigen, amino-oxononanoic acid synthase AONS, protein recombinase A RecA, acetyl- / propionyl-coenzyme A carboxylase alpha, alanine racemase, 60 kDa chaperonin 2, ESAT-6-like protein EcxB (L-ESAT-6), protein Lsr2, protein ML0276, heparin-binding hemagglutinin HBHA, heat shock protein 65 Hsp65, mycP1 or ML0041 coding protein htrA2 or ML0176 coding protein htrA4 or ML2659 coding protein gcp or ML0379 coding protein clpC or ML0235 coding protein (Mycobacterium leprae and Mycobacterium lepromatosis, leprosy);Outer membrane protein LipL32, membrane protein LIC10258, membrane protein LP30, membrane protein LIC12238, Ompa-like protein Lsa66, surface protein LigA, surface protein LigB, major outer membrane protein OmpL1, outer membrane protein LipL41, protein LigAni, surface protein LcpA, adhesion protein LipL53, outer membrane protein UpL32, surface protein Lsa63, flagellin FlaB1, membrane lipoprotein LipL21, membrane protein pL40, Leptospiral surface adhesin Lsa27, outer membrane protein OmpL36, outer membrane protein OmpL37, outer membrane protein OmpL47, outer membrane protein OmpL54, acyltransferase LpxA (Leptospira genus, leptospirosis); listeriolysin 0 precursor Hly (LL0), invasion-associated protein Iap (P60), listeriolysin regulatory protein PrfA, zinc metalloprotease Mpl, phosphatidylinositol-specific phospholipase C PLC (PIcA, PlcB), O-acetyltransferase Oat, ABC-transporter permease Im.G_1771, adhesion protein LAP, LAP receptor Hsp60, adhesin LapB, hemolysin listeriolysin O LLO, protein ActA, internalin A InIA, protein InIB (Listeria monocytogenes, Listeriosis); outer surface protein OspA, outer surface protein OspB, outer surface protein OspC, decorin-binding protein A DbpA, decorin-binding protein B DbpB, flagellar filament 41 kDa core protein Fla, basement membrane protein A BmpA (immunodominant antigen P39), outer surface 22 kDa lipoprotein precursor (antigen IPLA7), variable surface lipoprotein vlsE (usually Borrelia burgdorferi and other Borrelia species, Lyme disease (Lyme borreliosis));Venom allergen homolog-like protein VAL-1, abundant larval transcript ALT-1, abundant larval transcript ALT-2, thioredoxin peroxidase TPX, vespid allergen homolog VAH, thioredoxin peroxidase 2 TPX-2, antigenic protein SXP (peptides N, N1, N2, and N3), activation-associated protein-1 ASP-1, thioredoxin TRX, transglutaminase BmTGA, glutathione-S-transferase GST, myosin, vespid allergen homolog VAH, 175 kDa collagenase, glyceraldehyde-3-phosphate dehydrogenase GAPDH, cuticle collagen Col-4, secretory larval acidic proteins SLAPs, chitinase CHI-1, maltose-binding protein MBP, glycolytic enzyme fructose-1,6-bisphosphate aldolase Fba, tropomyosin TMY-1, nematode-specific gene product OvB20, onchocystatin CPI-2, protein Cox-2 (Wuchereria bancrofti and Brugia malayi, lymphatic filariasis (elephantiasis)); glycoprotein GP, ​​matrix protein polymerase L, nucleoprotein N (Lymphocytic choriomeningitis virus (LCMV), lymphocytic choriomeningitis);Thrombospondin-related anonymous protein TRAP, SSP2 Sporozoite surface protein 2, apical membrane antigen 1 AMA1, rhoptry membrane antigen RMA1, acidic-basic repeat antigen ABRA, cell-traversing protein PF, protein Pvs25, merozoite surface protein 1 MSP-1, merozoite surface protein 2 MSP-2, ring body-infected erythrocyte surface antigen RESALiver stage antigen 3 LSA-3, protein Eba-175, serine repeat antigen 5 SERA-5, circumsporozoite protein CS, merozoite surface protein 3 MSP3, merozoite surface protein 8 MSP5, enolase PF10, hepatocyte erythrocyte protein 17 kDa HEP17, erythrocyte membrane protein 1 EMP1, protein K beta merozoite surface protein 4 / 5 MSP 4 / 5, heat shock protein Hsp90, glutamic acid-rich protein GLURP, merozoite surface protein 4 MSP-4, protein STARP, circumsporozoite protein-related antigen precursor CRA (Plasmodium genus, malaria); nucleoprotein N, membrane-associated protein VP24, minor nucleoprotein VP30, polymerase cofactor VP35, polymerase L, matrix protein VP40, envelope glycoprotein GP (Marburg virus, Marburg hemorrhagic fever (MHF)); protein C, matrix protein M, phosphoprotein P, non-structural protein V, hemagglutinin glycoprotein H, polymerase L, nucleoprotein N, fusion protein F (Measles virus, measles);Members of the ABC transporter family (LoIC, OppA, and PotF), putative lipoprotein release system transmembrane protein LoIC / E, flagellin FliC, Burkholderia intracellular motility A BimA, bacterial elongation factor-Tu EF-Tu, 17 kDa OmpA-like protein, boaA coding protein, boaB coding protein (Burkholderia pseudomallei, melioidosis (Whitmore's disease)); Pilin protein, minor pilin-related subunit pilC, major pilin subunit and variants pilE, pilS, phase variant protein porA, porin B PorB, protein TraD, Neisserial outer membrane antigen H.8, 70 kDa antigen, major outer membrane protein PI, outer membrane proteins PIA and PIB, W antigen, surface protein A NspA, transferrin-binding protein TbpA, transferrin-binding protein TbpB PBP2, mtrR coding protein, ponA coding protein, membrane permease FbpBC, FbpABC protein system, LbpAB protein, outer membrane protein Opa, outer membrane transporter FetA, iron-repressible regulator MpeR, factor H-binding protein fHbp, adhesin NadA, protein NhbA, repressor FarR (Neisseria meningitidis, meningococcal disease); 66 kDa protein, 22 kDa protein (usually Metagonimus yokagawai, Metagonimiasis); polar tube proteins (34, 75, and 170 kDa in Glugea, 35, 55, and 150 kDa in Encephalitozoon), kinesin-related proteins, RNA polymerase II largest subunit, integral membrane protein analog YIPA, anti-silencing protein 1, heat shock transcription factor HSF, protein kinase, thymidine kinase, NOP-2-like nucleolar protein (Microsporidia phylum, Microsporidiosis);CASP8 and FADD-like apoptosis regulator, glutathione peroxidase GPX1, RNA helicase NPH-II NPH2, poly(A) polymerase catalytic subunit PAPL, major envelope protein P43K, early transcription factor 70 kDa subunit VETFS, early transcription factor 82 kDa subunit VETFL, metalloendopeptidase G1-type, nucleoside triphosphatase I NPH1, replication protein A28-like MC134L, RNA polymerase 7 kDa subunit RPO7 (Molluscum contagiosum virus (MCV)), Molluscum contagiosum (MC)); matrix protein M, phosphoprotein P / V, small hydrophobic protein SH, nucleoprotein N, protein V, fusion glycoprotein hemagglutinin-neuraminidase HN, RNA polymerase L (Mumps virus, Mumps); outer membrane protein OM, cell surface antigen OmpA, cell surface antigen OmpB (sca5), cell surface protein SCA4, cell surface protein SCA1, cytoplasmic protein D, crystalline surface layer protein SLP, protective surface protein antigen SPA (Rickettsia typhi, Murine typhus (Endemic typhus)); adhesin P1, adhesion P30, protein p116, protein P40, cytoskeletal protein HMW1, cytoskeletal protein HMW2, cytoskeletal protein HMW3, MPN152 coding protein, MPN426 coding protein, MPN456 coding protein, MPN-500 coding protein (Mycoplasma pneumoniae) pneumoniae), Mycoplasma pneumonia;NocA, iron-dependent regulatory protein; VapA, VapD, VapF, VapG, caseinolytic proteases; filament tip-associated 43-kDa protein; protein P24; protein P61; 15-kDa protein; 56-kDa protein (typically from Nocardia asteroides and other Nocardia species, nocardiosis); venom allergen homolog-like protein VAL-1; abundant larval transcript ALT-1; abundant larval transcript ALT-2; thioredoxin peroxidase TPX; hornet allergen homolog VAH; thioredoxin peroxidase 2 TPX-2; antigenic protein SXP (peptides N, N1, N2, and N3); activation-associated protein-1 ASP-1; thioredoxin TRX; transglutaminase BmTGA, glutathione-S-transferase; GST, myosin; vespid allergen homolog; VAH, 175 kDa collagenase; glyceraldehyde-3-phosphate dehydrogenase; GAPDH, cuticle collagen; Col-4, secreted larval acidic protein; SLAPs, chitinase; CHI-1, maltose-binding protein; MBP, glycolytic enzyme; fructose-1,6-bisphosphate aldolase; Fba, tropomyosin; TMY-1, nematode-specific gene product; OvB20, onchocystatin; CPI-2, Cox-2 (Onchocerca volvulus, onchocerciasis (river blindness));43 kDa secreted glycoprotein, glycoprotein gp0, glycoprotein gp75, antigen Pb27, antigen Pb40, heat shock protein Hsp65, heat shock protein Hsp70, heat shock protein Hsp90, protein P10, triosephosphate isomerase TPI, N-acetyl-glucosamine-binding lectin paracoccin, 28 kDa protein Pb28 (Paracoccidioides brasiliensis, Paracoccidioidomycosis (South American blastomycosis)); 28-kDa cruzipain-like cysteine ​​protease Pw28CCP (typically Paragonimus westermani) and other Paragonimus species, Paragonimiasis); outer membrane protein OmpH, outer membrane protein Omp28, protein PM1539, protein PM0355, protein PM1417, repair protein MutL, protein BcbC, protein (prtein) PM0305, formate dehydrogenase-N, protein PM0698, protein PM1422, DNA gyrase, lipoprotein PIpE, adhesion protein Cp39, heme acquisition system receptor HasR, 39 kDa coat protein, iron-regulated OMP IROMP, outer membrane protein OmpA87, fimbrial protein Ptf, fimbrial subunit protein PtfA, transferrin-binding protein Tbpl, esterase enzyme MesA, Pasteurella multocida toxin PMT, adhesion protein Cp39 (Pasteurella genus), Pasteurellosis);"Filamentous hemagglutinin FhaB, adenylate cyclase CyaA, pertussis toxin subunit 4 precursor PtxD, pertactin precursor Prn, toxin subunit 1 PtxA, protein Cpn60, protein brkA, pertussis toxin subunit 2 precursor PtxB, pertussis toxin subunit 3 precursor PtxC, pertussis toxin subunit 5 precursor PtxE, pertactin Pm, protein Fim2, protein Fim3" (Bordetella pertussis, Pertussis (Whooping cough)); "F1 capsule antigen, virulence-associated V antigen, secreted effector protein LcrV, V antigen, outer membrane protease Pla, secreted effector protein YopD, putative secreted protein-tyrosine phosphatase YopH, major subunit of needle complex YscF, protein kinase; YopO, putative autotransporter protein; YapF, inner membrane ABC-transporter; YbtQ (Irp7), putative carbohydrate-binding protein; YP00612, heat shock protein 90; HtpG, putative sulfatase protein; YdeN, outer membrane lipoprotein carrier protein; LoIA, secretion chaperone; YerA, putative lipoprotein; YP00420, hemolysin activator protein; HpmB, pesticin / yersiniabactin outer membrane receptor; Psn, secreted effector protein; YopE, secreted effector protein; YopF, secreted effector protein; YopK, outer membrane protein; YopN, outer membrane protein; YopM, coagulase / fibrinolysin precursor; Pla; (Yersinia pestis, Plague);Proteins PhpA, surface adhesin; PsaA, pneumolysin; Ply, ATP-dependent protease; CIp, lipoic acid-protein ligase; LpIA, cell wall surface anchor protein; psrP, sortase; SrtA, glutamyl-tRNA synthetase; GItX, choline-binding protein A; CbpA, pneumococcal surface protein A; PspA, pneumococcal surface protein C; PspC, 6-phosphogluconate dehydrogenase; Gnd, iron-binding protein; PiaA, murein hydrolase; LytB, protein; LytC, protease A1 (Streptococcus pneumoniae, pneumococcal infection); major surface protein B, kexin-like protease; KEX1; protein A12, 55 kDa antigen; P55, major surface glycoprotein; Msg (Pneumocystis jirovecii) jirovecii, Pneumocystis pneumonia (PCP); genome polyprotein, polymerase 3D, viral capsid protein VP1, viral capsid protein VP2, viral capsid protein VP3, viral capsid protein VP4, protease 2A, protease 3C (Poliovirus, Poliomyelitis); protein Nfa1, exendin-3, secretory lipase, cathepsin B-like protease, cysteine ​​protease, cathepsin, peroxiredoxin, protein CrylAc (typically Naegleria fowleri, primary amoebic meningoencephalitis (PAM)); agnoprotein, large T antigens, small T antigen, major capsid protein VP1, minor capsid protein Vp2 (JC virus, Progressive multifocal leukoencephalopathy);Low calcium response protein E LCrE, chlamydial outer protein N CopN, serine / threonine-protein kinase PknD, acyl-carrier protein S-malonyltransferase FabD, single-stranded DNA-binding protein Ssb, major outer membrane protein MOMP, outer membrane protein 2 Omp2, polymorphic membrane protein family (Pmp1, Pmp2, Pmp3, Pmp4, Pmp5, Pmp6, Pmp7, Pmp8, Pmp9, Pmp10, Pmp11, Pmp12, Pmp13, Pmp14, Pmp15, Pmp16, Pmp17, Pmp18, Pmp19, Pmp20, Pmp21) (Chlamydophila psittaci, Psittacosis); outer membrane protein P1, heat shock protein B HspB, peptide ABC Transporter, GTP-binding protein, protein IcmB, ribonuclease R, phosphatase SixA, protein DsbD, outer membrane protein ToIC, DNA-binding protein PhoB, ATPase DotB, heat shock protein B HspB, membrane protein ComI, 28 kDa protein, DNA-3-methyladenine glycosidase I, outer membrane protein OmpH, outer membrane protein AdaA, glycine cleavage system T-protein (Coxiella burnetii, Q fever); nucleoprotein N, large structural protein L, phosphoprotein P, matrix protein M, glycoprotein G (rabies virus, Rabies);Fusion protein F, nucleoprotein N, matrix protein M, matrix protein M2-1, matrix protein M2-2, phosphoprotein P, small hydrophobic protein SH, major surface glycoprotein G, polymerase L, non-structural protein 1 NS1, non-structural protein 2 NS2 (respiratory syncytial virus (RSV), respiratory syncytial virus infection); genome polyprotein, polymerase 3D, viral capsid protein VP1, viral capsid protein VP2, viral capsid protein VP3, viral capsid protein VP4, protease 2A, protease 3C (rhinovirus, rhinovirus infection); outer membrane protein OM, cell surface antigen OmpA, cell surface antigen OmpB (sca5), cell surface protein SCA4, cell surface protein SCA1, protein PS120, cytoplasmic protein D, protective surface protein antigen SPA (Rickettsia genus, Rickettsial infection); outer membrane protein OM, cell surface antigen OmpA, cell surface antigen OmpB (sca5), cell surface protein SCA4, cell surface protein SCA1, cytoplasmic protein D (Rickettsia akari, Rickettsialpox); Envelope glycoprotein GP, ​​polymerase L, nucleoprotein N, non-structural protein NSS (Rift Valley fever virus, Rift Valley fever (RVF)); outer membrane protein OM, cell surface antigen OmpA, cell surface antigen OmpB (sca5), cell surface protein SCA4, cell surface protein SCA1, cytoplasmic protein D (Rickettsia rickettsii, Rocky Mountain spotted fever (RMSF)); non-structural protein 6 N56, non-structural protein 2 N52, middle capsid protein VP6, inner capsid protein VP2, non-structural protein 3 NS3, RNA-directed RNA polymerase L, protein VP3, non-structural protein 1 NS1, non-structural protein 5 N55, outer capsid glycoprotein VP7, non-structural glycoprotein 4 N54, outer capsid protein VP4; (Rotavirus, Rotavirus infection); polyprotein P200, glycoprotein E1, glycoprotein E2, protein N52, capsid protein C (Rubella virus, Rubella); chaperonin GroEL (MopA), inositol phosphate phosphatase SopB, heat shock protein HslU, chaperone protein DnaJ, protein TviB, protein IroN, flagellin FliC, invasion protein SipC, glycoprotein gp43, outer membrane protein LamB, outer membrane protein PagC, outer membrane protein ToIC, outer membrane protein NmpC, outer membrane protein FadL, transport protein SadA, transferase WgaP, effector proteins SifA, SteC, SseL, SseJ, and SseF (Salmonella genus), Salmonellosis);Protein 14, non-structural protein NS7b, non-structural protein NS8a, protein 9b, protein 3a, nucleoprotein N, non-structural protein NS3b, non-structural protein N56, protein 7a, non-structural protein NS8b, membrane protein M, small envelope membrane protein EsM, replicase polyprotein 1a, spike glycoprotein S, replicase polyprotein lab; SARS coronavirus, SARS (Severe Acute Respiratory Syndrome); serine protease, atypical Sarcoptes antigen 1 ASAI, glutathione 5-transferase GST, cysteine ​​protease, serine protease, apolipoprotein (Sarcoptes scabiei, Scabies); glutathione 5-transferase GST, paramyosin, hemoglubinase SM32, major egg antigen, 14 kDa fatty acid-binding protein Sm14, major larval surface antigen P37, 22.6 kDa tegument antigen, calpain CANP, triphospate isomerase Tim, surface protein 9B, outer capsid protein VP2, 23 kDa integral membrane protein Sm23, Cu / Zn-superoxide dismutase, glycoprotein Gp, myosin (Schistosoma genus, Schistosomiasis (Bilharziosis)); 60 kDa chaperonin, 56 kDa type-specific antigen, pyruvate phosphate dikinase, 4-hydroxybenzoate octaprenyltransferase (Orientia tsutsugamushi, Scrub typhus);Dehydrogenase GuaB, invasion protein Spa32, invasin IpaA, invasin IpaB, invasin IpaC, invasin IpaD, invasin IpaH, invasin IpaJ (Shigella genus, Shigellosis (bacillary dysentery)); protein P53, virion protein US10 homolog, transcriptional regulator 1E63, transcriptional transactivator 1E62, protease P33, alpha trans-inducer 74 kDa protein, deoxyuridine 5′-triphosphate nucleotidyl hydrolase, transcriptional transactivator 1E4, membrane protein UL43 homolog, nuclear phosphoprotein UL3 homolog, nuclear protein UL4 homolog, origin-binding protein, membrane protein 2, phosphoprotein 32, protein 57, DNA Polymerase processivity factor, portal protein 54, DNA primase, tegument protein UL14 homolog, tegument protein UL21 homolog, tegument protein UL55 homolog, tripartite terminase subunit UL33 homolog, tripartite terminase subunit UL15 homolog, capsid-associated protein 44, virion-packaging protein 43 (Varicella zoster virus (VZV), Shingles (Herpes zoster));Truncated 3-beta-hydroxy-5-ene steroid dehydrogenase homolog, virion membrane protein A13, protein A19, protein A31, truncated protein A35 homolog, protein A37.5 homolog, protein A47, protein A49, protein A51, semaphorin-like protein A43, serine protease inhibitor 1, serine protease inhibitor 2, serine protease inhibitor 3, protein A6, protein B15, protein C1, protein C5, protein C6, protein F7, protein F8, protein F9, protein F11, protein F14, protein F15, protein F16 (Variola major or Variola minor, Smallpox (Variola)); adhesin / glycoprotein gp70, protease (Sporothrix schenckii, Sporotrichosis); heme-iron-binding protein IsdB, collagen adhesin Cna, clumping factor A CIfA, protein MecA, fibronectin-binding protein A FnbA, enterotoxin type A EntA, enterotoxin type B EntB, enterotoxin type C EntC1, enterotoxin type C EntC2, enterotoxin type D EntD, enterotoxin type E EntE, toxic shock syndrome toxin-1 TSST-1, staphylokinase, penicillin-binding protein 2a PBP2a (MecA), secretory antigen SssA (Staphylococcus genus, Staphylococcal food poisoning);Heme-iron binding protein IsdB, collagen adhesin Cna, clumping factor A CIfA, protein MecA, fibronectin-binding protein A FnbA, enterotoxin type A EntA, enterotoxin type B EntB, enterotoxin type C EntC1, enterotoxin type C EntC2, enterotoxin type D EntD, enterotoxin type E EntE, toxic shock syndrome toxin-1 TSST-1, staphylokinase, penicillin-binding protein 2a PBP2a (MecA), secretory antigen SssA (Staphylococcus genus, e.g., Staphylococcus aureus, Staphylococcal infection); antigen Ss-IR, antigen NIE, strongylastacin, Na+-K+ ATPase Sseat-6, tropomyosin SsTmy-1, protein LEC-5, 41 kDa antigen P5, 41-kDa larval protein, 31-kDa larval protein, 28-kDa larval protein (Strongyloides stercoralis, Strongyloidiasis); glycerophosphodiesterase GlpQ (Gpd), outer membrane protein TmpB, protein Tp92, antigen TpF1, repeat protein Tpr, repeat protein F TprF, repeat protein G TprG, repeat protein I Tprl, repeat protein J TprJ, repeat protein KTprK, treponemal membrane protein A TmpA, lipoprotein, 15 kDa Tpp15, 47 kDa membrane antigen, miniferritin TpF1, adhesin Tp0751, lipoprotein TP0136, protein TpN17, protein TpN47, outer membrane protein TP0136, outer membrane protein TP0155, outer membrane protein TP0326, outer membrane protein TP0483, outer membrane protein TP0956 (Treponema pallidum, Syphilis);Cathepsin L-like protease, 53 / 25-kDa antigen, 8 kDa family member, cysticercus protein with a marginal trypsin-like activity TsAg5, oncocyst protein TSOL18, oncocyst protein TSOL45-1A, lactate dehydrogenase A LDHA, lactate dehydrogenase B LDHB (Taenia genus, Taeniasis); tetanus toxin TetX, tetanus toxin C TTC, 140 kDa S-layer protein, flavoprotein beta-subunit CT3, phospholipase (lecithinase), phosphocarrier protein HPr (Clostridium tetani, Tetanus (Lockjaw)); genomic polyprotein, protein E, protein M, capsid protein C (Tick-borne encephalitis virus (TBEV)); 58-kDa antigen, 68-kDa antigen, Toxocara larva excretory-secretory antigen; TES, 32-kDa glycoprotein; glycoprotein TES-70; glycoprotein GP31; excretory-secretory antigen; TcES-57, periintestinal fluid antigen; Pe, soluble extractable antigen; Ex, excretory / secretory larval antigen; ES, antigen TES-120, polyprotein allergen; TBA-1, cathepsin L-like cysteine ​​protease c-cpl-1, 26-kDa protein (Toxocara canis or Toxocara cati); cati), Toxocariasis (Ocular Larva Migrans (OLM) and Visceral Larva Migrans (VLM));Microneme proteins (MIC1, MIC2, MIC3, MIC4, MIC5, MICE, MIC7, MICE), rhoptry protein Rop2, rhoptry proteins (Rop1, Rop2, Rop3, Rop4, Rop5, Rop6, Rop7, Rop16, Rjop17), protein SR1, surface antigen P22, major antigen p24, major surface antigen p30, dense granule proteins (GRA1, GRA2, GRA3, GRA4, GRA5, GRA6, GRA7, GRAB, GRA9, GRA10), 28 kDa antigen, surface antigen SAG1, SAG2-related antigen, nucleoside-triphosphatase 1, nucleoside-triphosphatase 2, protein Stt3, HesB-like domain-containing protein, rhomboid-like protease 5, toxomepsin 1 (Toxoplasma gondii, Toxoplasmosis); 43-kDa secreted glycoprotein, 53-kDa secreted glycoprotein, paramyosin, antigen Ts21, antigen Ts87, antigen p46000, TSL-1 antigen, caveolin-1 (CAV-1), 49-kDa neonatal larval antigen, prosaposin homolog, serine protease, serine protease inhibitor, 45-kDa glycoprotein Gp45 (Trichinella spiralis, Trichinellosis); Myb-like transcription factors (Mybl, Myb2, Myb3), adhesion protein AP23, adhesion protein AP33, adhesin protein AP33-3, adhesin AP51, adhesin AP65, adhesion protein AP65-1, alpha-actinin, kinesin-related protein, teneurin, 62 kDa protease, subtilisin-like serine protease SUB1, cysteine ​​protease gene 3 CP3, alpha-enolase Enol, cysteine ​​protease CP30, heat shock protein (Hsp70, Hsp60) immunogenic protein P270, (Trichomonas vaginalis, Trichomoniasis);beta-tubulin, 47-kDa protein, secretory leukocyte-like protease-1 SLP-1, 50-kDa protein TT50, 17 kDa antigen, 43 / 47 kDa protein (Trichuris trichiura, Trichuriasis (Whipworm infection))); protein ESAT-6 (EsxA), 10 kDa filtrate antigen EsxB, secretory antigen 85-B FBPB, fibronectin-binding protein A FbpA (Ag85A), serine protease PepA, PPE family protein PPE18, fibronectin-binding protein D FbpD, immunogenic protein MPT64, secretory protein MPT51, catalase-peroxidase-peroxynitritase T KATG, periplasmic phosphate-binding lipoprotein PSTS3 (PBP-3, Phos-1), iron-regulated heparin-binding hemagglutinin Hbha, PPE family·Ta; Protein PPE14, PPE family protein PPE68, protein Mtb72F, protein Apa, immunogenic protein MPT63, periplasmic phosphate-binding lipoprotein PSTS1 (PBP-1), molecular chaperone DnaK, cell surface lipoprotein Mpt83, lipoprotein P23, phosphate transport system permease protein pstA, 14 kDa antigen, fibronectin-binding protein C FbpC1, alanine dehydrogenase TB43, glutamine synthetase 1, ESX-1 protein, protein CFP10, TB10.4 protein, protein MPT83, protein MTB12, protein MTBE, Rpf-like protein, protein MTB32, protein MTB39, crystallin, heat shock protein HSP65, protein PST-S (typically associated with Mycobacterium tuberculosis, tuberculosis); outer membrane protein FobA, outer membrane protein FobB, intracellular growth locus IgIC1, intracellular growth locus IgIC2, aminotransferase Wbt1, chaperonin GroEL, 17 kDa major membrane protein TUL4, lipoprotein LpnA, chitinase family 18 protein, isocitrate dehydrogenase, Nif3 family protein, type IV pilin glycosylation protein, outer membrane protein toIC, FAD-binding family protein, type IV pilin multimeric outer membrane protein, two-component sensor protein KdpD, chaperone protein DnaK, protein TolQ (Francisella tularensis, Tularemia); "MB antigen," urease, protein GyrA, protein GyrB, protein ParC, protein ParE, lipid-associated membrane protein LAMP, thymidine kinase TK, phospholipase PL-A1, phospholipase PL-A2, phospholipase PL-C, surface-expressed 96-kDa antigen;(Ureaplasma urealyticum, Ureaplasma urealyticum infection); non-structural polyprotein, structural polyprotein, capsid protein CP, protein E1, protein E2, protein E3, protease Pb, protease P2, protease P3 (Venezuelan equine encephalitis virus, Venezuelan equine encephalitis); glycoprotein GP, ​​matrix protein Z, polymerase L, nucleoprotein N (Guanarito virus, Venezuelan hemorrhagic fever); polyprotein, protein E, protein M, capsid protein C, protease NS3, protein NS1, protein NS2A, protein AS2B, brotein NS4A, NS4B, and NS5 proteins (West Nile virus, West Nile fever); capsid protein CP, E1, E2, E3, and P2 protease (Western equine encephalitis virus, Western equine encephalitis); genome polyprotein, E protein, M protein, capsid protein C, and NS3 protease, NS1, NS2A, AS2B, NS4A, NS4B, and NS5 proteins (Yellow fever virus, Yellow fever);Putative Yop targeting protein YobB, effector protein YopD, effector protein YopE, protein YopH, effector protein YopJ, protein translocation protein YopK, effector protein YopT, protein YpkA, flagellar biogenesis protein FIhA, peptidase M48, potassium efflux system KefA, transcriptional regulator RovA, adhesin Ifp, translocator protein LcrV, protein PcrV, invasin Inv, outer membrane protein OmpF-like porin, adhesin YadA, protein kinase C, phospholipase C1, protein PsaA, mannosyltransferase-like protein WbyK, protein YscU, antigen YPMa (Yersinia pseudotuberculosis, Yersinia pseudotuberculosis infection); and effector protein YopB, 60 kDa chaperonin, protein WbcP, tyrosine-protein phosphatase YopH, protein YopQ, enterotoxin, galactoside permease, reductase NrdE, protein YasN, invasin Inv, adhesin YadA, outer membrane porin F OmpF, protein UspA1, protein EibA, protein Hia, cell surface protein Ail, chaperones SycD, protein LcrD, protein LcrG, protein LcrV, protein SycE, protein YopE, regulator protein TyeA, protein YopM, protein YopN, protein YopO, protein YopT, protein YopD, protease CIpP, protein MyfA, protein FilA, and protein PsaA (Yersinia enterocolitica, Yersiniosis);

[0096] The infectious agent may be a bacterium, a fungus, a virus, or a protozoan. The infectious agent may be a coronavirus (CoV) (e.g., an alphacoronavirus, a betacoronavirus, a gammacoronavirus, or a deltacoronavirus). Infectious disease agents include Acinetobacter baumannii, Anaplasma genus, Anaplasma phagocytophilum, Ancylostoma braziliense, Ancylostoma duodenale, Arcanobacterium haemolyticum, Ascaris lumbricoides, Aspergillus genus, Astroviridae, Babesia genus, Bacillus anthracis, Bacillus cereus, Bartonella henselae, and BK virus. virus, Blastocystis hominis, Blastomyces dermatitidis, Bordetella pertussis, Borrelia burgdorferi, Borrelia genus, Borrelia spp, Brucella genus, Brugia malayi, Bunyaviridae family, Burkholderia cepacia and other Burkholderia spp, Burkholderia mallei, Burkholderia pseudomallei, Caliciviridae family, Campylobactergenus, Candida albicans, Candida spp, Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, CJD prion, Clonorchis sinensis, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium perfringens, Clostridium spp, Clostridium tetani tetani, Coccidioides spp., coronaviruses, Corynebacterium diphtheriae, Coxiella burnetii, Crimean-Congo hemorrhagic fever virus, Cryptococcus neoformans, Cryptosporidium genus, Cytomegalovirus (CMV), Dengue viruses (DEN-1, DEN-2, DEN-3 and DEN-4), Dientamoeba fragilis, Ebola virus (EBOV), Echinococcus genus, Ehrlichia chaffeensis chaffeensis, Ehrlichia ewingii, Ehrlichia genus, Entamoeba histolytica, Enterococcus faecalisgenus, Enterovirus genus, Enteroviruses, mainly Coxsackie A virus and Enterovirus 71 (EV71), Epidermophyton spp, Epstein-Barr Virus (EBV), Escherichia coli O157:H7, O111, and O104:H4, Fasciola hepatica and Fasciola gigantica, FFI prion, Filarioidea superfamily, Filoviruses, Flaviviruses, Francisella tularensis, Fusobacterium genus, Geotrichum candidum, Giardia intestinalis, Gnathostoma spp, GSS prion, Guanarito virus, Haemophilus ducreyi, Haemophilus influenzae, Helicobacter pylori, Henipavirus (Hendra virus, Nipah virus), Hepatitis A virus, Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus, Hepatitis E virus, Herpes simplex virus 1 and 2 (HSV-1 and 2) HSV-2, Histoplasma capsulatum, HIV (human immunodeficiency virus), Hortaea werneckii, Human bocavirus (HBoV), Human herpesvirus 6(HHV-6) and human herpesvirus 7 (HHV-7), human metapneumovirus (hMPV), human papillomavirus (HPV), human parainfluenza viruses (HPIV), Japanese encephalitis virus, JC virus, Junin virus, Kingella kingae, Klebsiella granulomatis, Kuru prion, Lassa virus, Legionella pneumophila, Leishmania genus, Leptospira genus genus, Listeria monocytogenes, Lymphocytic choriomeningitis virus (LCMV), Machupo virus, Malassezia spp., Marburg virus, Measles virus, Metagonimus yokagawai, Microsporidia phylum, Molluscum contagiosum virus (MCV), Mumps virus, Mycobacterium leprae and Mycobacterium lepromatosis, Mycobacterium tuberculosis tuberculosis, Mycobacterium ulcerans, Mycoplasma pneumoniae, Naegleria fowlerifowleri, Necator americanus, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Nocardia spp, Onchocerca volvulus, Orientia tsutsugamushi, Orthomyxoviridae family (Influenza), Paracoccidioides brasiliensis, Paragonimus spp, Paragonimus westermani, Parvovirus B19, Pasteurella genus, Plasmodium spp. genus, Pneumocystis jirovecii, poliovirus, rabies virus, respiratory syncytial virus (RSV), rhinovirus, rhinoviruses, Rickettsia akari, Rickettsia genus, Rickettsia prowazekii, Rickettsia rickettsii, Rickettsia typhi, Rift Valley fever virus, rotavirus, Rubella virus, Sabia virus, Salmonella genus, Sarcoptes scabiei, SARS coronavirus, Schistosoma genus, Shigella genus, Sin Nombre virus, Hantavirus, Sporothrix schenkiischenckii, Staphylococcus genus, Staphylococcus genus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Strongyloides stercoralis, Taenia genus, Taenia solium, Tick-borne encephalitis virus (TBEV), Toxocara canis or Toxocara cati, Toxoplasma gondii, Treponema pallidum, Trichinella spiralis spiralis, Trichomonas vaginalis, Trichophyton spp, Trichuris trichiura, Trypanosoma brucei, Trypanosoma cruzi, Ureaplasma urealyticum, Varicella zoster virus (VZV), Variola major or Variola minor, vCJD prion, Venezuelan equine encephalitis virus, Vibrio cholerae, West Nile virus, Western equine encephalitis virus virus, Wuchereria bancrofti, Yellow fever virus, Yersinia enterocolitica, YersiniaThe bacterium may be selected from the group including: Mycobacterium pestis, and Yersinia pseudotuberculosis.

[0097] The AP may comprise or be derived from a full-length surface protein of a coronavirus. The disease or disorder may be an infectious disease or disorder caused by a coronavirus (CoV), and the AP may comprise or be derived from an antigenic protein of a coronavirus. As used in this application, the term "coronavirus" refers to viruses of the family Coronaviridae, which in turn are classified in the order Nidovirales. The coronaviruses are large, enveloped, positive-stranded RNA viruses. They have the largest genomes of any RNA virus known in the art and replicate by a unique mechanism that results in frequent recombination. The coronaviruses include antigenic groups I, II, and III. Non-limiting examples of coronaviruses include SARS coronaviruses (e.g., SARS-CoV and SARS-CoV-2), MERS coronavirus, transmissible gastroenteritis virus (TGEV), human respiratory coronavirus, porcine respiratory coronavirus, canine coronavirus, feline enteric coronavirus, feline infectious peritonitis virus, rabbit coronavirus, mouse hepatitis virus, These include sialodacryoadenitis virus, porcine hemagglutinating encephalomyelitis virus, bovine coronavirus, avian infectious bronchitis virus, and turkey coronavirus, as well as chimeras thereof. Further information on coronaviruses, including classification, virion structure, genome structure, genetics, and pathology, can be found, for example, in K. V. Holmes, Encyclopedia of Virology, 1999: 291-298, the contents of which are incorporated herein by reference.

[0098] In some embodiments, the coronaviruses described herein are in the genus Alpha-coronavirus, and the coronavirus antigens can be antigens of any species or strain, or can be derived from any species or strain, in the genus Alpha-coronavirus. In some embodiments, the coronaviruses described herein are in the genus Beta-coronavirus, and the coronavirus antigens can be antigens of any species or strain, or can be derived from any species or strain, in the genus Beta-coronavirus. Member viruses of the Alpha-coronavirus and Beta-coronavirus genera are enveloped, positive-strand RNA viruses that can infect mammals.

[0099] The coronaviruses described herein can be coronaviruses of any subgenus of the Alpha-coronavirus genus, including, but not limited to, Colacovirus (e.g., bat coronavirus CDPHE15), Decacovirus (e.g., bat coronavirus HKU10, and Rhinolophus ferrumequinum alphacoronavirus HuB-2013), Duvinacovirus (human coronavirus 229E), Luchacovirus (e.g., Lucheng Rn rat coronavirus), Minacovirus (e.g., mink coronavirus 1), Minunacovirus (e.g., Miniopterus bat coronavirus 1, and Miniopterus bat coronavirus HKU8). HKU8), Myotacovirus (e.g., Myotis ricketti alphacoronavirus Sax-2011), Nyctacovirus (e.g., Nyctalus velutinus alphacoronavirus SC-2013 and Pipistrellus kuhlii coronavirusu3398), Pedacovirus (e.g., porcine epidemic diarrhea virus and Scotophilus bat coronavirus512), Rhinacovirus (e.g., Rhinolophus bat coronavirus HKU2), Setracovirus (e.g., human coronavirusNL63, and the NL63-related bat coronavirus strain BtKYNL63-9b), Soracoviruses (e.g., Sorex araneus coronavirus T14), Sunacoviruses (e.g., Suncus murinus coronavirus X74), and Tegacoviruses (e.g., Alphacoronavirus 1).

[0100] Within the genus Beta-coronavirus, five subgenera or lineages are recognized, including, for example, Embecovirus (lineage A), Sarbecovirus (lineage B), Merbecovirus (lineage C), Nobecovirus (lineage D), and Hibecovirus. Thus, in some embodiments, the coronaviruses described in this application can be any strain or species within any of the Beta-coronavirus subgenera or lineages.

[0101] For example, coronavirus antigens can be antigens of any species or strain of, or can be derived from, any species or strain within the subgenus Embecovirus, including, but not limited to, Beta-coronavirus 1 (e.g., bovine coronavirus and human coronavirus OC43), Chinese rat coronavirus HKU24, human coronavirus HKU1, murine coronavirus (e.g., mouse hepatitis virus), and Myodes coronavirus 2JL14. Coronavirus antigens can be antigens of any species or strain of, or can be derived from, any species or strain within the subgenus Sarbecovirus. Examples of the subgenus of Sarbecovirus include, but are not limited to, SARS-CoV, SARS-CoV2, 16BO133, bat SARS-CoV Rf1, bat coronavirus HKU3 (BtCoV HKU3), LYRa11, bat SARS-CoV / Rp3, bat SL-CoV YNLF_31C, bat SL-CoV YNLF_34C, SHC014-CoV, WIV1, WIV16, civet cat SARS-CoV, Rc-o319, SL-ZXC21, SL-ZC45, pangolin SARSr-COV-GX, pangolin SARSr-COV-GD, RshSTT182, RshSTT200, RacCS203, RmYN02, RpYN06, Examples of coronavirus antigens include bat CoV RaTG13, bat CoV BtKY72, and bat CoV BM48-31. The coronavirus antigen may be of any species or strain in the subgenus Merbecovirus, or may be derived from any species or strain.Examples of the Merbecovirus subgenus include, but are not limited to, Hedgehog coronavirus 1, MERS-CoV, Pipistrellus bat coronavirus HKU5, and Tylonycteris bat coronavirus HKU4. The coronavirus antigen can be from or derived from any species or strain within the Nobecovirus subgenus. Examples of the Nobecovirus subgenus include, but are not limited to, Eidolon bat coronavirus C704, Rousettus bat coronavirus GCCDC1, and Rousettus bat coronavirus HKU9. The coronavirus antigen may be or may be derived from any species or strain in the subgenus Hibecovirus, including, but not limited to, Bat Hp-Betacoronavirus Zhejiang 2013.

[0102] The coronaviruses described herein can be phylogenetically clustered, for example, into functionally distinct clades. For example, coronaviruses of lineage B beta-coronaviruses (Sarbecoviruses) can be clustered into clade 1, clade 2, clade 1 / 2, or clade 3 using the nucleotide sequences of the nonstructural protein genes ORF1a and ORF1b (see, e.g., Hu et al., PLoS Pathog 13(11): e1006698). Thus, the coronavirus antigen can be any species antigen or strain antigen in any one of these clades, or can be derived from any species or strain. For example, the coronavirus antigen can be any species antigen or strain antigen in clade 1, including, but not limited to, SARS-CoV, WIV1, LYRa11, Rs7327, Rs4231, Rs4084, and SHC014. The coronavirus antigen can be any species antigen or any strain antigen in clade 2, including, but not limited to, As6526, Yunnan 2011, Shaanxi 2011, 279-2005, Rs4237, Rs4081, Rp3, Rs4247, HKU3-8, HKU3-13, GX2013, Longquan-140, YN2013, Rf4092, ZXC21, ZC45, JL2012, HuB2013, Rf1, HeB2013, and 273-2005. The coronavirus antigen can be any species antigen or any strain antigen in clade 1 / 2, including, but not limited to, SARS-CoV2. The coronavirus antigen can be an antigen of any species or any strain in clade 3, including, but not limited to, BM48-31. The coronavirus antigens described in this application can be antigens of coronaviruses (e.g., SARS, SARS-2, WIV1, SHC014, Rf1, RmYN02, pang17, RaTG13, and Rs4081).

[0103] As exemplified herein, SARS viruses (e.g., SARS-CoV and SARS-CoV-2) are enveloped coronaviruses possessing a single-stranded, positive-sense RNA genome (~30 kb) belonging to the genus Betacoronavirus from the family Coronaviridae. The viral RNA encodes four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, 16 non-structural proteins, and nine accessory proteins. The S glycoprotein contains an ectodomain, a transmembrane domain, and an intracellular domain that can be processed into S1 and S2 subunits. Both SARS-CoV and SARS-CoV-2 bind to human ACE2 via the receptor-binding domain in the S1 subunit, facilitating entry into host cells, followed by membrane fusion mediated by the S2 subunit.

[0104] Coronavirus antigens of the coronaviruses described herein can be any of a variety of coronavirus proteins capable of inducing an immune response against coronaviruses. Suitable coronavirus antigens are those capable of eliciting a protective immune response (e.g., generating broadly neutralizing antibodies). For example, the coronavirus antigen can include coronavirus spike (S) protein, spike receptor-binding domain (RBD), S1 subunit, S2 subunit, spike complete extracellular domain protein, papain-like protease, 3CL protease, nucleocapsid protein, envelope protein, membrane protein, or any structural, non-structural, or accessory protein that forms a coronavirus.

[0105] In some embodiments, coronavirus antigens used in the present application comprise spike (S) protein, or a portion thereof. S protein is one of four major structural proteins that coat the surface of each virion. S protein, comprising the S1 and S2 subunits, is a highly glycosylated type I transmembrane protein that can bind to host cell receptors and mediate viral entry. The S protein contains a domain called the RBD, which interacts with host cell receptors and mediates entry into the host cell after one or more RBDs assume an "up" position and bind to the host receptor. It is believed that after binding to the receptor, the spikes are cleaved by nearby host proteases, thereby releasing the spike fusion peptide and facilitating viral entry. Known host receptors for coronaviruses (e.g., beta-coronaviruses) include angiotensin-converting enzyme 2 (ACE2), dipeptidyl peptidase-4 (DPP4), or sialic acid. For example, the RBDs of the human coronaviruses SARS-CoV-2, SARS-CoV, HCoV-NL63, and related animal coronaviruses (WIV1 and SCH014) use ACE2 as their host receptor, whereas MERS-CoV uses DPP4 as its host receptor.

[0106] Coronavirus antigens used in the present application may include, for example, the coronavirus nucleocapsid protein (N protein), or portions thereof. The N protein is a multifunctional RNA-binding protein required for viral RNA transcription, replication, and packaging. The N protein consists of three domains: an N-terminal RNA-binding domain, a central intrinsically disordered region, followed by a C-terminal dimerization domain. The RNA-binding domain contains multiple positively charged binding surfaces that form charge interactions with RNA, promoting its helical configuration. Coronavirus antigens used in the present application may include any of these N protein regions, or portions thereof.

[0107] In some embodiments, the coronavirus antigens used in this application comprise the coronavirus membrane protein (M protein), or a portion thereof. The M protein is the most abundant structural protein and defines the shape of the viral envelope. The M protein is considered a central organizer of viral assembly and interacts with other major coronavirus structural proteins.

[0108] In some embodiments, the coronavirus antigens used in the present application include coronavirus envelope protein (E protein), or portions thereof. The E protein is a small membrane protein and a minor component of the viral particle. Without being bound by any theory, the E protein is thought to play a role in virion organization and morphogenesis, host cell membrane modification, and virus-host cell interactions.

[0109] In some embodiments, coronavirus antigens used in the present application include coronavirus hemagglutinin-esterase protein (HE protein), or a portion thereof, which is another envelope protein that mediates reversible binding to O-acetylated sialic acid by acting as both a lectin and a receptor-destroying enzyme.

[0110] In some embodiments, the coronavirus antigen used in the present application comprises a coronavirus papain-like protease, or a portion thereof. The coronavirus papain-like protease is one of several nonstructural proteins and is responsible for processing viral proteins into functional mature subunits during maturation. For example, the coronavirus papain-like protease can cleave a site at the amino-terminus of the viral replicase domain. In addition to its role in viral protein maturation, papain-like protease exhibits both deubiquitinating and de-ISG15-deconjugating activities. In vivo, this protease antagonizes innate immunity by affecting the IFN-beta and NF-κB signaling pathways.

[0111] In some embodiments, coronavirus antigens used herein comprise a coronavirus 3CL protease, or a portion thereof. The 3CL protease is another major protease in addition to the papain-like protease and is required for processing viral polypeptides into distinct, functional proteins. In some embodiments, the 3CL protease is the SARS-CoV-2 3CL protease, which is a C30-type cysteine ​​protease located within the non-structural protein 3 (NS3) region of the viral polypeptide. Analysis of the coronavirus genome reveals at least 11 cleavage sites for the 3CL protease, many of which contain the amino acid sequence LQ[S / A / G].

[0112] Coronavirus antigens disclosed in the present application may, in some embodiments, include an S protein or a portion thereof, an N protein or a portion thereof, an HE protein or a portion thereof, a papain-like protease or a portion thereof, a coronavirus 3CL protease or a portion thereof, an M protein or a portion thereof, or a combination thereof.

[0113] In some embodiments, the coronavirus antigen can be an immunogenic portion of a coronavirus protein described herein. Those skilled in the art will appreciate that the immunogenic portion of a coronavirus antigen can be a fragment of an S protein (e.g., spike protein RBD), an N protein, an HE protein, a papain-like protease, a 3CL protease, or an M protein that can elicit an immune response against one or more coronaviruses. The immunogenic portion can include about, at least about, at most about, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, or a number or range between any two of these values, of consecutive amino acid residues from the coronavirus protein. In some embodiments, the immunogenic portion comprises the S protein RBD, or a portion thereof, which may comprise a receptor binding motif of the S protein RBD.

[0114] One or more of the plurality of CoV antigens may be antigens of a CoV in the genus Alpha-CoV and / or Beta-CoV, and optionally each of the plurality of CoV antigens may be an antigen of a CoV in the genus Beta-CoV. The plurality of CoV antigens may be antigens of a CoV in the subgenus Sarbecovirus. The first CoV and the second CoV may be of the genus Beta-CoV, optionally of the subgenus Sarbecovirus. The multiple CoV antigens can be antigens of a CoV selected from the group consisting of: SARS-CoV, SARS-CoV-2, WIV1, SHC014, Rf1, RmYN02, pang17, RaTG13, Rs4081, LYRa11, HKU3, Yunnan2011, BtKY72, BM48-31, WIV16, Khosta-1, and Khosta-2. The first CoV, the second CoV, or both may be selected from the group consisting of: SARS-CoV, SARS-CoV-2, WIV1, SHC014, Rf1, RmYN02, pang17, RaTG13, Rs4081, LYRa11, HKU3, Yunnan2011, BtKY72, BM48-31, WIV16, Khosta-1, and Khosta-2. The CoV may be selected from species or subspecies of SARS-CoV, SARS-CoV-1, SARS-CoV-2, MERS-CoV, SL-CoV-WIVl, HKU4, HKU5, HCoV-OC43, HCoV-HKUl, HKU9, HKU3, HKU8, HKU24, NL63, SHC014, 229E and / or SARS-CoV-2 variants B.1.351, B.1.1.7, P.1, B.1.617.2, B.1.1.529, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and other descendant lineages.

[0115] The CoV may be selected from a species or subspecies of Embecovirus, Sarbecovirus, Merbecovirus, Nobevovirus, Hibecovirus, SARSr-CoV, MERS-CoV, or any combination thereof. The CoV may be selected from a beta-CoV from the sarbe-, embeco-, merbeco-, and / or nobecovirus lineages. The CoV may be selected from a sarbecovirus strain, optionally SARS, LYRa11, Rf1, Rs4081, BtKY72, and / or BM48-31. The CoV may be selected from a merbecovirus strain, optionally HKU4, HKU5, HKU25, BtCoV-Vs-CoV1, MERS-associated NL13845, MERS-associated NL140422. The CoV may be selected from an embecovirus strain, optionally HKU1, Rat CoV Parker, PHEV, Equine CoV, Rodent CoV, Longquan Rat CoV.

[0116] Tumor-associated antigens, autoimmune antigens, and allergic antigens The disease or disorder may be a disease associated with expression of a tumor-associated antigen, and the antigenic protein may be a tumor-associated antigen. The tumor-associated antigen may be a tumor-specific antigen. In some embodiments, the tumor-associated antigen is selected from the group comprising: 1A01_HLA-A / m (UniProtKB: P30443); 1A02 (UniProtKB: P01892); 5T4 (UniProtKB: Q13641); ACRBP (UniProtKB: Q8NEB7); AFP (UniProtKB: P02771); AKAP4 (UniProtKB: Q5JQC9); alpha-actinin-_4 / m (UniProtKB: B4DSX0); alpha-actinin-_4 / m (UniProtKB: B4E337); alpha-actinin-_4 / m (UniProtKB: 043707); alpha-methylacyl-coenzyme_A_racemase (UniProtKB: A0A024RE16); alpha-methylacyl-coenzyme_A_racemase. (UniProtKB: A8KAC3); ANDR (UniProtKB: P10275); ART-4 (UniProtKB: Q9ULX3); ARTC1 / m (UniProtKB: P52961); AURKB (UniProtKB: Q96GD4); B2MG (UniProtKB: P61769); B3GN5 (UniProtKB: Q9BYGO); B4GN1 (UniProtKB: Q00973); B7H4 (UniProtKB: Q7Z7D3); BAGE-1 (UniProtKB: Q13072); BASI (UniProtKB: P35613); BCL-2 (UniProtKB: A9QXG9); bcr / abl (UniProtKB: A9UEZ4); bcr / abl (UniProtKB: A9UEZ7); bcr / abl (UniProtKB: A9UEZ8); bcr / abl (UniProtKB: A9UEZ9); bcr / abl (UniProtKB: A9UF00); bcr / abl (UniProtKB: A9UF01); bcr / abl (UniProtKB: A9UF03);bcr / abl (UniProtKB: A9UF04); bcr / abl (UniProtKB: A9UF05); bcr / abl (UniProtKB: A9UF06); bcr / abl (UniProtKB: A9UF08); beta-catenin / m (UniProtKB: P35222); beta-catenin / m (UniProtKB: Q8WYA6); BING-4 (UniProtKB: 015213); BIRC7 (UniProtKB: Q96CA5); BRCA1 / m (UniProtKB: A0A024R1V0); BRCA1 / m (UniProtKB: A0A024R1V7); BRCA1 / m (UniProtKB: A0A024R1Z8); BRCA1 / m (UniProtKB: A0A068BFX7); BRCA1 / m (UniProtKB: C6YB45); BRCA1 / m (UniProtKB: C6YB47); BRCA1 / m (UniProtKB: G3XAC3); BY55 (UniProtKB: 095971); calreticulin (UniProtKB: B4DHR1); calreticulin (UniProtKB: B4E2Y9); calreticulin (UniProtKB: P27797); calreticulin (UniProtKB: Q96L12); CAMEL (UniProtKB: 095987); CASP-8 / m (UniProtKB: Q14790); CASPA (UniProtKB: Q92851-4); cathepsin_B (UniProtKB: A0A024R374); cathepsin_B (UniProtKB: P07858); cathepsin_L (UniProtKB: A0A024R276); Cathepsin_L (UniProtKB: P07711); Cathepsin_L (UniProtKB: Q9HBQ7); CD1A (UniProtKB: P06126); CD1B (UniProtKB: P29016); CD1C (UniProtKB: P29017); CD1D (UniProtKB: P15813); CD1E (UniProtKB: P15812); CD20 (UniProtKB: P11836);CD22 (UniProtKB: 060926); CD22 (UniProtKB: P20273); CD22 (UniProtKB: QOEAF5); CD276 (UniProtKB: Q5ZPR3); CD33 (UniProtKB: B4DF51); CD33 (UniProtKB: P20138); CD33 (UniProtKB: Q546G0); CD3E (UniProtKB: P07766); CD3Z (UniProtKB: P20963); CD44_アイソフォーム_1 (UniProtKB: P16070); CD44_アイソフォーム_6 (UniProtKB: P16070-6); CD4 (UniProtKB: P01730); CD52 (UniProtKB: P31358); CD52 (UniProtKB: Q6IBDO); CD52 (UniProtKB: V9HWN9); CD55 (UniProtKB: B1AP15); CD55 (UniProtKB: D3DT85); CD55 (UniProtKB: D3DT86); CD55 (UniProtKB: P08174); CD56 (UniProtKB: P13591); CD80 (UniProtKB: AONOP2); CD80 (UniProtKB: P33681); CD86 (UniProtKB: P42081); CD8A (UniProtKB: P01732); CDCl27 / m (UniProtKB: G5EA36); CDCl27 / m (UniProtKB: P30260); CDE30 (UniProtKB: P28908); CDK4 / m (UniProtKB: A0A024RBB6); CDK4 / m (UniProtKB: P11802); CDK4 / m (UniProtKB: Q6LC83); CDK4 / m (UniProtKB: Q96BE9); CDKN2A / m (UniProtKB: D1LYX3); CDKN2A / m (UniProtKB: G3XAG3); CDKN2A / m (UniProtKB: K7PML8); CDKN2A / m (UniProtKB: L8E941); CDKN2A / m (UniProtKB: Q8N726);CEA (RefSeq: NP_004354); CEAM6 (UniProtKB: P40199); CH3L2 (UniProtKB: Q15782); CLCA2 (UniProtKB: Q9UQC9); CML28 (UniProtKB: Q9NQT4); CML66 (UniProtKB: Q96RS6); COA-1 / m (UniProtKB: Q5T124); coactosin-like protein (UniProtKB: Q14019); collagen_XXIII (UniProtKB: L8EAS4); collagen_XXIII (UniProtKB: Q86Y22); COX-2 (UniProtKB: Q6ZYK7); CP1B1 (UniProtKB: Q16678); CSAG2 (UniProtKB: Q9Y5P2-2); CSAG2 (UniProtKB: Q9Y5P2); CT45A1 (UniProtKB: Q5HYN5); CT55 (UniProtKB: Q8WUE5); CT-_9 / BRD6 (UniProtKB: Q58F21); CTAG2_isoform_LAGE-1A (UniProtKB: 075638-2); CTAG2_isoform_LAGE-1B (UniProtKB: 075638); CTCFL (UniProtKB: Q8NI51); Cten (UniProtKB: Q8IZW8); cyclin_B1 (UniProtKB: P14635); cyclin_D1 (UniProtKB: P24385); cyp-B (UniProtKB: P23284); DAM-10 (UniProtKB: P43366); DEP1A (UniProtKB: Q5TB30); E7 (UniProtKB: P03129); E7 (UniProtKB: P06788); E7 (UniProtKB: P17387); E7 (UniProtKB: P06429); E7 (UniProtKB: P27230); E7 (UniProtKB: P24837); E7 (UniProtKB: P21736); (UniProtKB: P26558);E7 (UniProtKB: P36831); E7 (UniProtKB: P36833); E7 (UniProtKB: Q9QCZ1); E7 (UniProtKB: Q81965); E7 (UniProtKB: Q80956); EF1A2 (UniProtKB: Q05639); EFTUD2 / m (UniProtKB: Q15029); EGFR (UniProtKB: A0A0B4J1Y5); EGFR (UniProtKB: E7BSVO); EGFR (UniProtKB: LOR6G1); EGFR (UniProtKB: P00533-2); EGFR (UniProtKB: P00533); EGFR (UniProtKB: Q147T7); EGFR (UniProtKB: Q504U8); EGFR (UniProtKB: Q8NDU8); EGLN3 (UniProtKB: Q9H6Z9); ELF2 / m (UniProtKB: B7Z720); EMMPRIN (UniProtKB: Q54A51); EpCam (UniProtKB: P16422); EphA2 (UniProtKB: P29317); EphA3 (UniProtKB: P29320); EphA3 (UniProtKB: Q6P4R6); ErbB3 (UniProtKB: B3KWG5); ErbB3 (UniProtKB: B4DGQ7); ERBB4 (UniProtKB: Q15303); ERG (UniProtKB: P11308); ETV6 (UniProtKB: P41212); EWS (UniProtKB: Q01844); EZH2 (UniProtKB: F2YMM1); EZH2 (UniProtKB: G3XAL2); EZH2 (UniProtKB: LOR855); EZH2 (UniProtKB: Q15910); EZH2 (UniProtKB: S4S3R8); FABP7 (UniProtKB: 015540); FCGR3A_バージョン_1 (UniProtKB: P08637); FCGR3A_バージョン_2 (CCDS: CCDS1232.1); FGFS (UniProtKB: P12034);FGFS (UniProtKB: Q60518); FGFR2 (UniProtKB: P21802); Fibronectin (UniProtKB: A0A024R5I6); Fibronectin (UniProtKB: A0A024RB01); Fibronectin (UniProtKB: A0A024RDT9); Fibronectin (UniProtKB: A0A024RDV5); Fibronectin (UniProtKB: A6NH44); Fibronectin (UniProtKB: A8K6A5); Fibronectin (UniProtKB: B2R627); Fibronectin (UniProtKB: B3KXM5); Fibronectin (UniProtKB: B4DIC5); Fibronectin (UniProtKB: B4DN21); Fibronectin (UniProtKB: B4DS98); Fibronectin (UniProtKB: B4DTH2); fibronectin (UniProtKB: B4DTK1); fibronectin (UniProtKB: B4DU16); fibronectin (UniProtKB: B7Z3W5); fibronectin (UniProtKB: B7Z939); fibronectin (UniProtKB: G5E9X3); fibronectin (UniProtKB: Q9H382); FOS (UniProtKB: P01100); FOXP3 (UniProtKB: Q9BZS1); FUT1 (UniProtKB: P19526); G250 (UniProtKB: Q16790); GAGE-1 (Genbank: AAA82744); GAGE-2 (UniProtKB: Q6NT46); GAGE-3 (UniProtKB: Q13067); GAGE-4 (UniProtKB: GAGE-5 (UniProtKB: Q13069); GAGE-6 (UniProtKB: Q13070); GAGE7b (UniProtKB: 076087); GAGE-8_(GAGE-2D) (UniProtKB: Q9UEU5); GASR (UniProtKB: P32239); GnT-V (UniProtKB: Q09328);GPC3 (UniProtKB: I6QTG3); GPC3 (UniProtKB: P51654); GPC3 (UniProtKB: Q8IYG2); GPNMB / m (UniProtKB: A0A024RA55); GPNMB / m (UniProtKB: Q14956); GPNMB / m (UniProtKB: Q8IXJ5); GPNMB / m (UniProtKB: Q96F58); GRM3 (UniProtKB: Q14832); HAGE (UniProtKB: Q9NXZ2); ヘプシン (UniProtKB: B2ZDQ2); ヘプシン (UniProtKB: P05981); Her2 / neu (UniProtKB: B4DTR1); Her2 / neu (UniProtKB: L8E8G2); Her2 / neu (UniProtKB: P04626); Her2 / neu (UniProtKB: Q9UK79); HLA-A2 / m (UniProtKB: Q95387); HLA-A2 / m (UniProtKB: Q9MYF8); ホメオボックス_NKX3.1 (UniProtKB: Q99801); HOM-TES-85 (UniProtKB: B2RBQ6); HOM-TES-85 (UniProtKB: Q9P127); HPG1 (Pubmed: 12543784); HS71A (UniProtKB: PODMV8); HS71B (UniProtKB: PODMV9); HST-2 (UniProtKB: P10767); hTERT (UniProtKB: 094807); iCE (UniProtKB: 000748); IF2B3 (UniProtKB: 000425); IL10 (UniProtKB: P22301); IL-13Ra2 (UniProtKB: Q14627); IL2-RA (UniProtKB: P01589); IL2-RB (UniProtKB: P14784); IL2-RG (UniProtKB: P31785); IL-5 (UniProtKB: P05113); IMP3 (UniProtKB: Q9NV31); ITA5 (UniProtKB: P08648);ITB1 (UniProtKB: P05556); ITB6 (UniProtKB: P18564); kallikrein-2 (UniProtKB: A0A024R4J4); kallikrein-2 (UniProtKB: A0A024R4N3); kallikrein-2 (UniProtKB: BOAZU9); kallikrein-2 (UniProtKB: B4DU77); kallikrein-2 (UniProtKB: P20151); kallikrein-2 (UniProtKB: Q6T774); kallikrein-2 (UniProtKB: Q6T775); kallikrein-4 (UniProtKB: A0A0C4DFQ5); kallikrein-4 (UniProtKB: Q5BQA0); kallikrein-4 (UniProtKB: Q96PTO); kallikrein-4 (UniProtKB: Q96PT1); Kallikrein-4 (UniProtKB: Q9Y5K2); KI20A (UniProtKB: 095235); KIAA0205 (UniProtKB: Q92604); KIF2C (UniProtKB: Q99661); KK-LC-1 (UniProtKB: Q5H943); LDLR (UniProtKB: LGMN (UniProtKB: Q99538); LIRB2 (UniProtKB: Q8N423); LY6K (UniProtKB: Q17RY6); MAGAS (UniProtKB: P43359); MAGA8 (UniProtKB: P43361); MAGAB (UniProtKB: P43364); MAGE-A10 (UniProtKB: A0A024RC14); MAGE-A12 (UniProtKB: P43365); MAGE-A1 (UniProtKB: P43355); MAGE-A2 (UniProtKB: P43356); MAGE-A3 (UniProtKB: P43357); MAGE-A4 (UniProtKB: A0A024RC12); (UniProtKB: Q1RN33); MAGE-A6 (UniProtKB: A8K072);MAGE-A6 (UniProtKB: P43360); MAGE-A6 (UniProtKB: Q6FHI5); MAGE-A9 (UniProtKB: P43362); MAGE-B10 (UniProtKB: Q96LZ2); MAGE-B16 (UniProtKB: A2A368); MAGE-B17 (UniProtKB: A8MXT2); MAGE-_B1 (UniProtKB: Q96TG1); MAGE-B2 (UniProtKB: 015479); MAGE-B3 (UniProtKB: 015480); MAGE-B4 (UniProtKB: 015481); MAGE-B5 (UniProtKB: Q9BZ81); MAGE-B6 (UniProtKB: Q8N7X4); MAGE-C1 (UniProtKB: 060732); MAGE-C2 (UniProtKB: Q9UBF1); MAGE-C3 (UniProtKB: Q8TD91); MAGE-D1 (UniProtKB: Q9Y5V3); MAGE-D2 (UniProtKB: Q9UNF1); MAGE-D4 (UniProtKB: Q96JG8); MAGE-_E1 (UniProtKB: Q6IAI7); MAGE-E1_(MAGE1) (UniProtKB: Q9HCI5); MAGE-E2 (UniProtKB: Q8TD90); MAGE-F1 (UniProtKB: Q9HAY2); MAGE-H1 (UniProtKB: Q9H213); MAGEL2 (UniProtKB: Q9U355); マンマグロビン_A (UniProtKB: Q13296); マンマグロビン_A (UniProtKB: Q6NX70); MART-1 / メラン(melan)-A (UniProtKB: Q16655); MART-2 (UniProtKB: Q5VTY9); MC1_R (UniProtKB: Q01726); MC1_R (UniProtKB: Q1JUL4); MC1_R (UniProtKB: Q1JUL6); MC1_R (UniProtKB: Q1JUL8); MC1_R (UniProtKB: Q1JUL9); MC1_R (UniProtKB: Q1JUM0);MC1_R (UniProtKB: Q1JUM2); MC1_R (UniProtKB: Q1JUM3); MC1_R (UniProtKB: Q1JUM4); MC1_R (UniProtKB: Q1JUM5); MC1_R (UniProtKB: Q6UR92); MC1_R (UniProtKB: Q6UR94); MC1_R (UniProtKB: Q6UR95); MC1_R (UniProtKB: Q6UR96); MC1_R (UniProtKB: Q6UR97); MC1_R (UniProtKB: Q6UR98); MC1_R (UniProtKB: Q6UR99); MC1_R (UniProtKB: Q6URA0); MC1_R (UniProtKB: Q86YW1); MC1_R (UniProtKB: V9Q5S2); MC1_R (UniProtKB: V9Q671); MC1_R (UniProtKB: V9Q783); MC1_R (UniProtKB: V9Q7F1); MC1_R (UniProtKB: V9Q8N1); MC1_R (UniProtKB: V9Q977); MC1_R (UniProtKB: V9Q9P5); MC1_R (UniProtKB: V9Q9R8); MC1_R (UniProtKB: V9QAE0); MC1_R (UniProtKB: V9QAR2); MC1_R (UniProtKB: V9QAW3); MC1_R (UniProtKB: V9QB02); MC1_R (UniProtKB: V9QB58); MC1_R (UniProtKB: V9QBY6); MC1_R (UniProtKB: V9QC17); MC1_R (UniProtKB: V9QC66); MC1_R (UniProtKB: V9QCQ4); MC1_R (UniProtKB: V9QDF4); MC1_R (UniProtKB: V9QDN7); MC1_R (UniProtKB: V9QDQ6); M-CSF (UniProtKB: P09603); メソテリン (UniProtKB: Q13421); MITF (UniProtKB: 075030-8); MITF (UniProtKB: 075030-9); MITF (UniProtKB: 075030); MMP1_1 (UniProtKB: B3KQS8); MMP7 (UniProtKB: P09237); MUC-1 (Genbank: AAA60019); MUM-1 / m (RefSeq: NP_116242); MUM-2 / m (UniProtKB: Q9Y5R8); MYCN (UniProtKB: P04198); MY01A (UniProtKB: Q9UBC5); MY01B (UniProtKB: 043795); MY01C (UniProtKB: 000159); MYO1D (UniProtKB: 094832); MY01E (UniProtKB: Q12965); MY01F (UniProtKB: 000160); MY01G (UniProtKB: B0I1T2); MY01H (RefSeq: NP_001094891); NA17 (UniProtKB: Q3V5L5); NA88-A (Pubmed: 10790436); Neo-PAP (UniProtKB: Q9BWT3); NFYC / m (UniProtKB: Q13952); NGEP (UniProtKB: Q6IWH7); NPM (UniProtKB: P06748); NRCAM (UniProtKB: Q92823); NSE (UniProtKB: P09104); NUF2 (UniProtKB: Q9BZD4);NY-ESO-1 (UniProtKB: P78358); 0A1 (UniProtKB: P51810); OGT (UniProtKB: 015294); OS-9 (UniProtKB: B4DH11); OS-9 (UniProtKB: B4E321); OS-9 (UniProtKB: B7Z8E7); OS-9 (UniProtKB: Q13438); osteocalcin (UniProtKB: P02818); osteopontin (UniProtKB: A0A024RDE2); osteopontin (UniProtKB: A0A024RDE6); osteopontin (UniProtKB: A0A024RDJ0); osteopontin (UniProtKB: B7Z351); osteopontin (UniProtKB: F2YQ21); osteopontin (UniProtKB: P10451); p53 (UniProtKB: P04637); PAGE-4 (UniProtKB: 060829); PAI-1 (UniProtKB: P05121); PAI-2 (UniProtKB: P05120); PAP (UniProtKB: Q06141); PAP (UniProtKB: Q53S56); PATE (UniProtKB: Q8WXA2); PAX3 (UniProtKB: P23760); PAXS (UniProtKB: Q02548); PD1L1 (UniProtKB: Q9NZQ7); PDCD1 (UniProtKB: Q15116); PDEF (UniProtKB: 095238); PECA1 (UniProtKB: P16284); PGCB (UniProtKB: Q96GW7); PGFRB (UniProtKB: P09619); Pim-1_-kinase (UniProtKB: A0A024RD25); Pin-1 (UniProtKB: 015428); Pin-1 (UniProtKB: Q13526); Pin-1 (UniProtKB: Q49AR7); PLAC1 (UniProtKB: Q9HBJ0); PMEL (UniProtKB: P40967); PML (UniProtKB: P29590);POTEF (UniProtKB: A5A3E0); POTE (UniProtKB: Q86YR6); PRAME (UniProtKB: A0A024R1E6); PRAME (UniProtKB: P78395); PRDX5 / m (UniProtKB: P30044); PRM2 (UniProtKB: P04554); Prostein (UniProtKB: Q96JT2); Proteinase-3 (UniProtKB: D6CHE9); Proteinase-3 (UniProtKB: P24158); PSA (UniProtKB: P55786); PSB9 (UniProtKB: P28065); PSCA (UniProtKB: D3DWI6); PSCA (UniProtKB: 043653); PSGR (UniProtKB: Q9H255); PSM (UniProtKB: Q04609); PTPRC (RefSeq: NP_002829); RAB8A (UniProtKB: P61006); RAGE-1 (UniProtKB: Q9UQ07); RARA (UniProtKB: P10276); RASH (UniProtKB: P01112); RASK (UniProtKB: P01116); RASN (UniProtKB: P01111); RGSS (UniProtKB: 015539); RHAMM / CD168 (UniProtKB: 075330); RHOC (UniProtKB: P08134); RSSA (UniProtKB: P08865); RU1 (UniProtKB: Q9UHJ3); RU2 (UniProtKB: Q9UHG0); RUNX1 (UniProtKB: Q01196); S-100 (UniProtKB: V9HW39); SAGE (UniProtKB: Q9NXZ1); SART-_1 (UniProtKB: 043290); SART-2 (UniProtKB: Q9UL01); SART-3 (UniProtKB: Q15020); SEPR (UniProtKB: Q12884); SERPINBS (UniProtKB: P36952);SIA7F (UniProtKB: Q969X2); SIA8A (UniProtKB: Q92185); SIAT9 (UniProtKB: Q9UNP4); SIRT2 / m (UniProtKB: A0A024ROG8); SIRT2 / m (UniProtKB: Q8IXJ6); SOX10 (UniProtKB: P56693); SP17 (UniProtKB: Q15506); SPNXA (UniProtKB: Q9NS26); SPXN3 (UniProtKB: Q5MJ09); SSX-1 (UniProtKB: Q16384); SSX-2 (UniProtKB: Q16385); SSX3 (UniProtKB: Q99909); SSX-4 (UniProtKB: 060224); ST1A1 (UniProtKB: P50225); STAG2 (UniProtKB: Q8N3U4-2); STAMP-1 (UniProtKB: Q8NFT2); STEAP-1 (UniProtKB: A0A024RA63); STEAP-1 (UniProtKB: Q9UHE8); サバイビン-2B (UniProtKB: 015392-2); サバイビン (UniProtKB: 015392); SYCP1 (UniProtKB: A0A024R0I2); SYCP1 (UniProtKB: B7ZLS9); SYCP1 (UniProtKB: Q15431); SYCP1 (UniProtKB: Q3MHC4); SYT-SSX-1 (UniProtKB: A4PIV7); SYT-SSX-1 (UniProtKB: A4PIV8); SYT-SSX-2 (UniProtKB: A4PIV9); SYT-SSX-2 (UniProtKB: A4PIWO); TARP (UniProtKB: QOVGM3); TCRg (UniProtKB: A2JGV3); TF2AA (UniProtKB: P52655); TGFB1 (UniProtKB: P01137); TGFR2 (UniProtKB: P37173); TGM-4 (UniProtKB: B2R7D1); TIE2 (UniProtKB: Q02763);TKIL1 (UniProtKB: P51854); TPI / m (UniProtKB: P60174); TRGV11 (UniProtKB: Q99601); TRGV9 (UniProtKB: A4D1X2); TRGV9 (UniProtKB: Q99603); TRGV9 (UniProtKB: Q99604); TRPC1 (UniProtKB: P48995); TRP-p8 (UniProtKB: Q7Z2W7); TSG10 (UniProtKB: Q9BZW7); TSPY1 (UniProtKB: Q01534); TVC_(TRGV3) (Genbank: M13231.1); TX101 (UniProtKB: Q9BY14-2); tyrosinase (UniProtKB: A0A024DBG7); L8B082); tyrosinase (UniProtKB: L8B086); tyrosinase (UniProtKB: L8B0B9); tyrosinase (UniProtKB: 075767); tyrosinase (UniProtKB: P14679); tyrosinase (UniProtKB: U3M8N0); tyrosinase (UniProtKB: U3M9D5); tyrosinase (UniProtKB: U3M9J2); TYRP1 (UniProtKB: P17643); TYRP2 (UniProtKB: P40126); UPA (UniProtKB: Q96NZ9); VEGFR1 (UniProtKB: B5A924); WT1 (UniProtKB: A0A0H5AUY0); WT1 (UniProtKB: P19544); WT1 (UniProtKB: Q06250); and XAGE1 (UniProtKB: Q9HD64). ;

[0117] The disease or disorder may be an autoimmune disease or disorder, and the antigenic protein may be an autoimmune antigen, such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG), each associated with multiple sclerosis (MS); CD44, preproinsulin, proinsulin, insulin, glutamic acid decaroxylase (GAD65), tyrosine phosphatase-like insulinoma antigen 2 (IA2), zinc transporter (ZnT8), and heat shock protein 60 (HSP60), each associated with type 1 diabetes; or interphotoreceptor retinoid-binding protein (IRB), associated with autoimmune uveitis. (IRBP); acetylcholine receptor AchR, and insulin-like growth factor-1 receptor (IGF-1R), (each associated with myasthenia gravis); M-protein (pseudoautoantigen) from beta-hemolytic streptococci associated with rheumatic fever, or any combination thereof. The autoimmune antigen (antigen associated with an autoimmune disease or autoantigen) is selected from autoantigens associated with an autoimmune disease selected from the following: Addison's disease (autoimmune adrenalitis, Morbus Addison), alopecia areata, Addison's anemia (Morbus Biermer), autoimmune hemolytic anemia(AIHA), cold autoimmune hemolytic anemia (AIHA) (cold hemagglutinin disease), cold autoimmune hemolytic anemia (AIHA) (cold agglutinin disease), (CHAD), warm autoimmune hemolytic anemia (AIHA) (warm AIHA), warm autoimmune hemolytic anemia (AIHA), autoimmune hemolytic Donath-Landsteiner anemia (paroxysmal cold hemoglobinuria), antiphospholipid syndrome (APS), atherosclerosis, autoimmune arthritis, temporal arteritis, Takayasu's arteritis (Takayasu's disease, aortic arch disease), temporal arteritis / giant cell arteritis, autoimmune chronic gastritis, autoimmune infertility, autoimmune inner ear disease (AIED), Graves' disease (Morbus Basedow), Bechterew's disease (Morbus Bechterew), ankylosing spondylitis, spondylitis ankylosans, Behcet's syndrome (Morbus Behcet), intestinal diseases including autoimmune inflammatory bowel disease (including ulcerative colitis), cardiomyopathies, especially autoimmune cardiomyopathy, idiopathic dilated cardiomyopathy (DCM), celiac sprue dermatitis (gluten mediated enteropathia), chronic fatigue immune dysfunction syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy (CIDP), chronic polyarthritis, Churg-Strauss syndrome, cicatricial pemphigoid, Cogan syndromesyndrome), CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal motility disorder, sklerodaktylia and teleangiectasia), Crohn's disease (Morbus Crohn, ulcerative colitis), Dermatitis herpetiformis during Dühring, autoimmune skin diseases, dermatomyositis, diabetes, Diabetes mellitus Type 1 (type I diabetes, insulin-dependent diabetes), Diabetes mellitus Type 2 (type II diabetes) diabetes), essential mixed cryoglobulinemia, essential mixed cryoglobulinemia, fibromyalgia, fibromyositis, Goodpasture's syndrome (anti-GBM mediated glomerulonephritis), graft-versus-host disease, Guillain-Barré syndrome (GBM, Polyradikuloneuritis), blood autoimmune diseases, Hashimoto's thyroiditis, hemophilia, acquired hemophilia, hepatitis, autoimmune hepatitis, especially autoimmune chronic hepatitis, idiopathic pulmonary fibrosis (IPF), idiopathic thrombocytopenic purpura, immune-thrombocytopenic purpura (Morbus Werlhof disease, ITP), IgA nephropathy, infertility, autoimmune infertility, juvenile rheumatoid arthritis (Morbus Still, Still syndrome), Lambert-Eaton syndrome syndrome), lichen planus, lichen sclerosus, lupus erythematosus, systemic lupus erythematosus (SLE), lupus erythematosus (disc type), Lyme arthritis (Lyme disease, Borrelia arthritis), Meniere's disease (Morbus Meniere); mixed connective tissue disease (MCTD); multiple sclerosis (MS, disseminated encephalomyelitis)disseminate, Charcot's disease), myasthenia gravis (MG), myositis, polymyositis, neurological autoimmune diseases, neurodermatitis, pemphigus vulgaris, bullous pemphigoid, scar-forming pemphigoid; polyarteritis nodosa (periarteritis nodosa), polychondritis (panchondritis), polyglandular (autoimmune) syndrome (PGA syndrome, Schmidt's syndrome), polymyalgia rheumatica, primary agammaglobulinemia, primary biliary cirrhosis (PBC), primary autoimmune cholangitis, progressive systemic sclerosis sclerosis (PSS), psoriasis, plaque psoriasis, Raynaud's phenomenon, Reiter's syndrome (Morbus Reiter, urethroconjunctival synovial syndrome), rheumatoid arthritis (RA, chronic polyarthritis, rheumatic disease of the joints, rheumatic fever), sarcoidosis (Morbus Boeck, Besnier-Boeck-Schaumann disease), stiff-man syndrome, scleroderma, Sjogren's syndrome, sympathetic ophthalmia; transient gluten intolerance, transplant organ rejection, uveitis, autoimmune uveitis, vasculitis, vitiligo, (leucoderma, piebold skin), and Wegner's disease (Morbus Wegner, Wegener's granulomatosis).

[0118] The disease or disorder may be an allergic disease or disorder, and the antigenic protein may be an allergic antigen. In some embodiments, the allergenic antigen may be selected from the group comprising: Acarus spp. (Aca s 1, Aca s 10, Aca s 10.0101, Aca s 13, Aca s 13.0101, Aca s 2, Aca s 3, Aca s 7, Aca s 8), Acanthocybium spp. (Aca so 1), Acanthocheilonema spp. (Aca v 3, Aca v 3.0101), Acetes spp. (Ace ja 1), Actinidia spp. (Act a 1, Act c 1, Act c 10, Act c 10.0101, Act c 2, Act c 4, Act c 5, Act c 5.0101, Act c 8, Act c 8.0101, Act c chitinase, Act d 1, Act d 1.0101, Act d 10, Act d 10.0101, Act d 10.0201, Act d 11, Act d 11.0101, Act d 2, Act d 2.0101, Act d 3, Act d 3.0101, Act d 3.02, Act d 4, Act d 4.0101, Act d 5, Act d 5.0101, Act d 6, Act d 6.0101, Act d 7, Act d 7.0101, Act d 8, Act d 8.0101, Act d 9, Act d 9.0101, Act d chitinase, Act e 1, Act e 5), Acyrthosiphon spp (Acy pi 7, Acy pi 7.0101, Acy pi 7.0102), Adenia spp (Ade v RIP), Aedes spp (Aed a 1, Aed a 1.0101, Aed a 2, Aed a 2.0101, Aed a 3, Aed a 3.0101, Aed a 4, Aed a 7, Aed a 7.0101, Aed a 7.0102, Aed a 7.0103, Aed a 7.0104, Aed a 7.0105, Aed a 7.0106, Aed a 7.0107, Aed a 7.0108, Aed a 7.0109, Aed a 7.0110, Aed a 7.0111, Aed al 1, Aed al 3, Aed al 37 kD, Aed v 37 kD, Aed v 63 kD), Aegilops spp. (Aeg ta 28, Aeg ta alpha_gliadin, Aeg um 28, Aeg un 28), Aethaloperca spp. (Aet ro 1), Agropyron spp. (Agr c 7), Agrostis spp. (Agr ca 1, Agr ca 5, Agr g 1, Agr g 4, Agr s 5), Agrobacterium spp. (Agr sp CP4 EPSPS), Ailuropoda spp. (Ail me phosvitin, Ail me TCTP), Mandarin duck spp. (Aix ga 1, Aix sp 1), Aleuroglyphus spp. (Ale o 1, Ale o 10, Ale o 10.0101, Ale o 10.0102, Ale o 13, Ale o 14, Ale o 2, Ale o 20, Ale o 3, Ale o 5, Ale o 7, Ale o 8, Ale o 9), Allium spp. (All a 3, All a alliin lyase, All c 3, All c 30 kD, All c 4, All c alliin lyase, All p alliin lyase, All s alliin lyase), Alnus spp. (Aln g 1, Aln g 1.0101, Aln g 1 / Bet v 1 / Cor a 1 TPC7, Aln g 1 / Bet v 1 / Cor a 1 TPC9, Aln g 2, Aln g 4, Aln g 4.0101), Alopochen spp (Alo ae 1), Alopecurus spp (Alo p 1, Alo p 5), Alternaria spp (Alt a 1, Alt a 1.0101, Alt a 1.0102, Alt a 10, Alt a 10.0101, Alt a 12, Alt a 12.0101, Alt a 13, Alt a 13.0101, Alt a 2, Alt a 3, Alt a 3.0101, Alt a 4, Alt a 4.0101, Alt a 5, Alt a 5.0101, Alt a 6, Alt a 6.0101, Alt a 7, Alt a 7.0101, Alt a 70 kD, Alt a 8, Alt a 8.0101, Alt a 9, Alt a MnSOD, Alt a NTF2, Alt a TCTP, Alt ar 1, Alt arg 1, Alt b 1, Alt bl 1, Alt br 1, Alt c 1, Alt ca 1, Alt ce 1, Alt ch 1, Alt ci 1, Alt co 1, Alt cr 1, Alt ct 1, Alt cu 1, Alt cy 1, Alt d 1, Alt du 1, Alt e 1, Alt et 1, Alt eu 1, Alt ga 1, Alt gr 1, Alt j 1, Alt l 1, Alt lo 1, Alt m 1, Alt me 1, Alt mi 1, Alt mo 1, Alto 1, Alt p 1, Alt ph 1, Alt po 1, Alt ps 1, Alt r 1, Alt s 1, Alt se 1, Alt sm 1, Alt so 1, Alt su 1, Alt t 1, Alt to 1, Alt to 1), Amaranthus spp (Ama r 2, Ama r 2.0101, Ama v 2, Ama v 2.0101, Ama v 2.0201), Ambrosia spp (Amb a 1, Amb a 1.0101, Amb a 1.0201, Amb a 1.0202, Amb a 1.0301, Amb a 1.0302, Amb a 1.0303, Amb a 1.0304, Amb a 1.0305, Amb a 1.0401, Amb a 1.0402, Amb a 1.0501, Amb a 1.0502, Amb a 10, Amb a 10.0101, Amb a 3, Amb a 3.0101, Amb a 4, Amb a 4.0101, Amb a 5, Amb a 5.0101, Amb a 6, Amb a 6.0101, Amb a 7, Amb a 7.0101, Amb a 8, Amb a 8.0101, Amb a 8.0102, Amb a 9, Amb a 9.0101, Amb a 9.0102, Amb a CPI, Amb p 1, Amb p 5, Amb p 5.0101, Amb p 5.0201, Amb t 5, Amb t 5.0101, Amb t 8), Ammothea spp (Amm h 7, Amm h 7.0101), Anadara spp (Ana br 1), Ananas spp (Ana c 1, Ana c 1.0101, Ana c 2, Ana c 2.0101, Ana c 2.0101 (MUXF3)), Anas spp (Ana ca 1), Anarhichas spp (Ana I 1), Anacardium spp (Ana o 1, Ana o 1.0101, Ana o 1.0102, Ana o 2, Ana o 2.0101, Ana o 3, Ana o 3.0101), Anas spp. (Ana p 1, Ana p 2, Ana p 3), Anguilla spp. (Ang a 1, Ang j 1), Anisakis spp. (Ani s 1, Ani s 1.0101, Ani s 10, Ani s 10.0101, Ani s 11, Ani s 11.0101, Ani s 12, Ani s 12.0101, Ani s 2, Ani s 2.0101, Ani s 24 kD, Ani s 3, Ani s 3.0101, Ani s 4, Ani s 4.0101, Ani s 5, Ani s 5.0101, Ani s 6, Ani s 6.0101, Ani s 7, Ani s 7.0101, Ani s 8, Ani s 8.0101, Ani s 9, Ani s 9.0101, Ani s CCOS3, Ani s Cytochrome B, Ani s FBPP, Ani s NADHDS4L, Ani s NARaS, Ani s PEPB, Ani s troponin), Annona spp (Ann c chitinase), Anopheles spp (Ano da 17, Ano da 17.0101, Ano da 27, Ano da 27.0101, Ano da 7, Ano da 7.0101, Ano g 7, Ano g 7.0101), Anser spp. (Ans a 1, Ans a 2, Ans a 3, Ans in 1), Anthoxanthum spp. (Ant o 1, Ant o 1.0101, Ant o 12, Ant o 13, Ant o 2, Ant o 4, Ant o 5, Ant o 6, Ant o 7), Apis spp. (Api c 1, Api c 1.0101, Api c 10, Api c 2, Api c 4, Api d 1, Api d 1.0101, Api d 4, Api fl 4), Apium spp. (Api g 1, Api g 1.0101, Api g 1.0201, Api g 2, Api g 2.0101, Api g 3, Api g 3.0101, Api g 4, Api g 4.0101, Api g 5, Api g 5.0101, Api g 6, Api g 6.0101), Apis spp (Api m 1, Api m 1.0101, Api m 10, Api m 10.0101, Api m 11, Api m 11.0101, Api m 11.0201, Api m 13 kD, Api m 2, Api m 2.0101, Api m 3, Api m 3.0101, Api m 4, Api m 4.0101, Api m 5, Api m 5.0101, Api m 6, Api m 6.0101, Api m 7, Api m 7.0101, Api m 8, Api m 8.0101, Api m 9, Api m 9.0101, Api m A1 - A2, Api m A1 - A2 - A3, Api m apalbumin 1, Api m apalbumin 2, Api me 1, Api me 4), Arachis spp (Ara d 2, Ara d 6, Ara f 3, Ara f 4, Ara h 1, Ara h 1.0101, Ara h 10, Ara h 10.0101, Ara h 10.0102, Ara h 11, Ara h 11.0101, Ara h 2, Ara h 2.0101, Ara h 2.0102, Ara h 2.0201, Ara h 2.0202, Ara h 3, Ara h 3.0101, Ara h 4, Ara h 4.0101, Ara h 5, Ara h 5.0101, Ara h 6, Ara h 6.0101, Ara h 7, Ara h 7.0101, Ara h 7.0201, Ara h 7.0202, Ara h 8, Ara h 8.0101, Ara h 8.0201, Ara h 9, Ara h 9.0101, Ara h 9.0201, Ara h agglutinin Ara h oleosin 18 kD, Ara i 2, Ara i 6), Arabidopsis spp. (Ara t 3, Ara t 8, Ara t GLP), Archosargus spp. (Arc pr 1), Archaeopotamobius spp. (Arc s 8, Arc s 8.0101), Aequipecten spp. (Arg i 1), Argas spp. (Arg r 1, Arg r 1.0101), Ariopsis spp. (Ari fe 1), Armoracia spp. (Arm r HRP), Arrhenatherum spp. (Arr e 1, Arr e 5), Artemisia spp. (Art a 1, Art ap 1), Artemia spp. (Art fr 1, Art fr 1.0101, Art fr 5, Art fr 5.0101), Arthrobacter spp. (Art gl CO), Achorion spp. (Art gy 7), Artocarpus spp. (Art h 17 kD, Art h 4), Arthrospira spp. (Art pl beta_phycocyanin), Artemisia spp. (Art v 1, Art v 1.0101, Art v 1.0102, Art v 1.0103, Art v 1.0104, Art v 1.0105, Art v 1.0106, Art v 1.0107, Art v 2, Art v 2.0101, Art v 3, Art v 3.0101, Art v 3.0201, Art v 3.0202, Art v 3.0301, Art v 4, Art v 4.0101, Art v 4.0201, Art v 47 kD, Art v 5, Art v 5.0101, Art v 6, Art v 6.0101, Art v 60 kD), Arthroderma spp (Art va 4), Ascaris spp (Asc 13, Asc 1 3.0101, Asc 1 3.0102, Asc 1 34 kD, Asc s 1, Asc s 1.0101, Asc s 3, Asc s 3.0101, Asc s GST), Aspergillus spp (Asp aw glucoamylase, Asp c 22, Asp f 1, Asp f 1.0101, Asp f 10, Asp f 10.0101, Asp f 11, Asp f 11.0101, Asp f 12, Asp f 12.0101, Asp f 13, Asp f 13.0101, Asp f 15, Asp f 15.0101, Asp f 16, Asp f 16.0101, Asp f 17, Asp f 17.0101, Asp f 18, Asp f 18.0101, Asp f 2, Asp f 2.0101, Asp f 22, Asp f 22.0101, Asp f 23, Asp f 23.0101, Asp f 27, Asp f 27.0101, Asp f 28, Asp f 28.0101, Asp f 29, Asp f 29.0101, Asp f 3, Asp f 3.0101, Asp f 34, Asp f 34.0101, Asp f 4, Asp f 4.0101, Asp f 5, Asp f 5.0101, Asp f 56 kD, Asp f 6, Asp f 6.0101, Asp f 7, Asp f 7.0101, Asp f 8, Asp f 8.0101, Asp f 9, Asp f 9.0101, Asp f AfCalAp, Asp f AT_V, Asp f catalase, Asp f chitosanase, Asp f CP, Asp f DPPV, Asp f FDH, Asp f gamma_actin, Asp f glucosidase, Asp f GPI, Asp f GST, Asp f GT, Asp f IAO, Asp f IPMI, Asp f LPL1, Asp f LPL3, Asp f mannosidase, Asp f MDH, Asp f PL, Asp f PUP, Asp f RPS3, Asp f SXR, Asp fl 13, Asp fl 13.0101, Asp fl 18, Asp fl 2, Asp fl 21, Asp fl 3, Asp fl 4, Asp fl 7, Asp fl 8, Asp fl 9, Asp me prase (Sea prose), Asp n 14, Asp n 14.0101, Asp n 18, Asp n 18.0101, Asp n 25, Asp n 25.0101, Asp n 30, Asp n glucoamylase, Asp n hemicellulase, Asp n pectinase, Asp o 13, Asp o 13.0101, Asp o 21, Asp o 21.0101, Asp o 3, Asp o 4, Asp o 7, Asp o 8, Asp o lactase, Asp o lipase, Asp oc 13, Asp r 1, Asp sa AP, Asp sp glucoamylase, Asp sp glucose oxidase, Asp sp PL, Asp sp PME, Asp sy 13, Asp v 13, Asp v 13.0101, Asp v catalase A, Asp v enolase, Asp v GAPDH, Asp v MDH, Asp v SXR), Asparagus spp. (Aspa o 1, Aspa o 1.01, Aspa o 1.02, Aspa o 17 kD, Aspa o 4), Aspergillus spp. (Aspe ni 2, Aspe ni 3, Aspe ni 4, Aspe ni 7, Aspe ni 8, Aspe ni 9), Avena spp. (Ave s 1, Ave s 12, Ave s 13, Ave s 2, Ave s 4, Ave s 5, Ave s 7), Babylonia spp. (Bab ja 1), Bacillus spp. (Bac al subtilisin, Bac cl subtilisin, Bac I subtilisin, Bac II aA, Bac II subtilisin), Bactrocera spp. spp) (Bac ol 27, Bac ol 27.0101), Bacillus spp (Bac sp aA1, Bac sp aA3, Bac sp decarboxylase, Bac st amyM, Bac su subtilisin, Bac t CrylAb, Bac t CrylFa, Bac t Cry3Bb1, Bac t Cry9c), Bagre spp (Bag ma 1), Balistes spp (Bal ca 1), Balanus spp (Bal r 1, Bal r 1.0101), Beauveria spp (Bea b AId, Bea b Enol, Bea b f2, Bea b Hex), Bertholletia spp. (Ber e 1, Ber e 1.0101, Ber e 2, Ber e 2.0101), Beryx spp. (Ber sp 1),. Species of the genus Betula (Betula spp) (Bet ab 1, Bet al 1, Bet ch 1, Bet co 1, Bet da 1, Bet gr 1, Bet hu 1, Bet le 1, Bet me 1, Bet n 1, Bet p 1, Bet pa 1, Bet po 1, Bet pu 1, Bet pu 2, Bet pu 4, Bet pu 6, Bet pu 7, Bet sc 1, Bet ut 1, Bet v 1, Bet v 1 B1-131-131, Bet v 1 fv Mal 4x, Bet v 1.0101, Bet v 1.0102, Bet v 1.0103, Bet v 1.0201, Bet v 1.0301, Bet v 1.0401, Bet v 1.0402, Bet v 1.0501, Bet v 1.0601, Bet v 1.0602, Bet v 1.0701, Bet v 1.0801, Bet v 1.0901, Bet v 1.1001, Bet v 1.1101, Bet v 1.1201, Bet v 1.1301, Bet v 1.1401, Bet v 1.1402, Bet v 1.1501, Bet v 1.1502, Bet v 1.1601, Bet v 1.1701, Bet v 1.1801, Bet v 1.1901, Bet v 1.2001, Bet v 1.2101, Bet v 1.2201, Bet v 1.2301, Bet v 1.2401, Bet v 1.2501, Bet v 1.2601, Bet v 1.2701, Bet v 1.2801, Bet v 1.2901, Bet v 1.3001, Bet v 1.3101, Bet v 2, Bet v 2.0101, Bet v 3, Bet v 3.0101, Bet v 4, Bet v 4.0101, Bet v 6, Bet v 6.0101, Bet v 6.0102, Bet v 7, Bet v 7.0101, Bet v 8, Bet v glucanase), species of the genus Beta (Beta spp) (Beta v 1, Beta v 1.0101, Beta v 2, Beta v 2.Blattella spp (Bla g 1, Bla g 1.0101, Bla g 1.0102, Bla g 1.0103, Bla g 1.0201, Bla g 1.0202, Bla g 2, Bla g 2.0101, Bla g 2.0201, Bla g 36 kD, Bla g 4, Bla g 4.0101, Bla g 4.0201, Bla g 5, Bla g 5.0101, Bla g 5.0201, Bla g 6, Bla g 6.0101, Bla g 6.0201, Bla g 6.0301, Bla g 7, Bla g 7.0101, Bla g 8, Bla g 8.0101, Bla g 9, Bla g enolase, Bla g GSTD1, Bla g RACK1, Bla g TPI, Bla g trypsin, Bla g vitellogenin), Blatta spp. (Bla o 1, Bla o 7), Blomia spp. (Blo t 1, Blo t 1.0101, Blo t 1.0201, Blo t 10, Blo t 10.0101, Blo t 10.0102, Blo t 11, Blo t 11.0101, Blo t 12, Blo t 12.0101, Blo t 12.0102, Blo t 13, Blo t 13.0101, Blo t 14, Blo t 15, Blo t 18, Blo t 19, Blo t 19.0101, Blo t 2, Blo t 2.0101, Blo t 2.0102, Blo t 2.0103, Blo t 20, Blo t 21, Blo t 21.0101, Blo t 3, Blo t 3.0101, Blo t 4, Blo t 4.0101, Blo t 5, Blo t 5.0101, Blo t 6, Blo t 6.0101, Blo t 7, Blo t 8, Blo t 9, Blo t HSP70), Bombus spp (Bom ar 4, Bom by 4, Bom p 1, Bom p 1.0101, Bom p 2, Bom p 3, Bom p 4, Bom p 4.0101, Bom t 1, Bom t 1.0101, Bom t 4, Bom t 4.0101), Bombyx spp. (Bomb m 1, Bomb m 1.0101, Bomb m 7, Bomb m 7.0101, Bomb m 7.0102, Bomb m 7.0103, Bomb m 7.0104, Bomb m 7.0105, Bomb m 7.0106), Boophilus spp. (Boo m 1, Boo m 7, Boo m 7.0101), Bos spp. (Bos d 2, Bos d 2.0101, Bos d 2.0102, Bos d 2.0103, Bos d 3, Bos d 3.0101, Bos d 4, Bos d 4.0101, Bos d 5, Bos d 5.0101, Bos d 5.0102, Bos d 6, Bos d 6 (MDA), Bos d 6.0101, Bos d 7, Bos d 7.0101, Bos d 8, Bos d 8 alphaSl, Bos d 8 alphaS2, Bos d 8 beta, Bos d 8 kappa, Bos d alpha2I, Bos d alpha2I.0101, Bos d chymosin, Bos d fibrin, Bos d gelatin, Bos d HG, Bos d insulin, Bos d lactoferrin, Bos d lactoperoxidase, Bos d myoglobin, Bos d OBP, Bos d OSCP, Bos d phosvitin, Bos d PLA2, Bos d PRVB, Bos d thrombin, Bos d TI, Bos gr ALA, Bos gr myoglobin), Bothrops spp (Bot as 1, Bot at 1), Bouteloua spp (Bou g 1), Biting spp (Boy ov 1), Brama spp (Bra du 1), Brassica spp (Bra j 1, Bra j 1.0101, Bra n 1, Bra n 1.0101, Bra n 4, Bra n 7, Bra n 8, Bra n PG, Bra ni 8, Bra o 3, Bra o 3.0101, Bra r 1, Bra r 1.0101, Bra r 2, Bra r 2.0101, Bra r 3, Bra r 4, Bra r 7), Bromus spp. (Bro a 1, Bro a 4), Brosme spp. (Bro br 1), Bromus spp. (Bro i 1, Bro i 5, Bro i 7), Brugia spp. (Bru m 3, Bru m 3.0101, Bru m Bm33), Asian buffalo species (Bubalus spp) (Bub b ALA, Bub b BLG, Bub b casein, Bub b casein alpha S1, Bub b casein alpha S2, Bub b casein beta, Bub b casein kappa), Caenorhabditis spp (Cae b 3, Cae b 3.0101, Cae br 3, Cae br 3.0101, Cae e 3, Cae e 3.0101, Cae e 3.0102, Cae re 13, Cae re 13.0101), Pigeonpea species (Cajanus spp) (Caj c 1), Caligus spp (Cal cl 1, Cal cl 1.0101, Cal cl 1.0102), Calamus spp. (Cal le 1), Callinectes spp. (Cal s 2), Camelus spp. (Cam d ALA, Cam d casein, Cam d casein alpha S1, Cam d casein alpha S2, Cam d casein beta, Cam d casein kappa), Camponotus spp. (Cam fl 7, Cam fl 7.0101), Canis spp. (Can f 1, Can f 1.0101, Can f 2, Can f 2.0101, Can f 3, Can f 3.0101, Can f 4, Can f 4.0101, Can f 5, Can f 5.0101, Can f 6, Can f 6.0101, Can f Feld1-like, Can f Homs2-like, Can f phosvitin, Can f TCTP), Canthidermis spp. (Can ma 1), Cancer spp. (Can mg 2, Can p 1), Cannabis spp. (Can s 3), Candida spp. (Cand a 1, Cand a 1.0101, Cand a 3, Cand a 3.0101, Cand a CAAP, Cand a CyP, Cand a enolase, Cand a FPA, Cand a MnSOD, Cand a PGK, Cand b 2, Cand b 2.0101, Cand b FDH, Cand r lipase), Capsicum spp. (Cap a 1, Cap a 1.0101, Cap a 17 kD, Cap a 2, Cap a 2.0101, Cap a 30 kD, Cap a glucanase, Cap ch 17 kD), Caprella spp. (Cap e 1), Capra spp. (Cap h ALA, Cap h BLG, Cap h casein, Cap h casein alpha S1, Cap h casein alpha S2, Cap h casein beta, Cap h casein kappa, Cap h GSA), Capitulum spp. (Cap m 1), Carassius spp. (Car au 1), Carpinus spp. 1.0110, Car b 1.0111, Car b 1.Car b 1.0112, Car b 1.0113, Car b 1.0201, Car b 1.0301, Car b 1.0302, Car b 2, Car b 4), Caranx spp. (Car cr 1), Carya spp. (Car i 1, Car i 1.0101, Car i 2, Car i 4, Car i 4.0101), Carcinus spp. (Car ma 2), Caryota spp. (Car mi 2), Carica spp. (Car p 1, Car p chitinase, Car p chymopapain, Car p endoproteinase), Castanea spp. (Cas c 24 kD, Cas s 1, Cas s 1.0101, Cas s 1.0102, Cas s 1.0103, Cas s 2, Cas s 5, Cas s 5.0101, Cas s 8, Cas s 8.0101, Cas s 9, Cas s 9.0101), Catharanthus spp. (Cat r 1, Cat r 1.0101, Cat r 17 kD, Cat r 2), Caulolatilus spp. (Cau ch 1), Cavia spp. (Cav p 1, Cav p 1.0101, Cav p 2, Cav p 2.0101, Cav p 3, Cav p 3.0101, Cav p gelatin, Cav p GSA), Centropristis spp. (Cen s 1), Cephalopholis spp. (Cep so 1), Charybdis spp. (Cha f 1, Cha f 1.0101), Chaetodipterus spp. (Cha fa 1), Chamaecyparis spp. (Cha o 1, Cha o 1.0101, Cha o 2, Cha o 2.0101), Chenopodium spp. (Che a 1, Che a 1.0101, Che a 2, Che a 2.0101, Che a 3, Che a 3.0101), Chironomus spp (Chi k 1, Chi k 10, Chi k 10.0101), Chinchilla spp (Chi I 21 kD_a, Chi I 21 kD_b), Chionoecetes spp (Chi o 1, Chi o 1.0101, Chi o 2, Chi o 4, Chi o 6, Chi o アルファ_アクチン, Chi o SERCA), Chironomus spp (Chi t 1, Chi t 1.0101, Chi t 1.0201, Chi t 2, Chit 2.0101, Chit 2.0102, Chit 3, Chit 3.0101, Chit 4, Chit 4.0101, Chit 5, Chit 5.0101, Chit 6, Chit 6.0101, Chit 6.0201, Chit 7, Chit 7.0101, Chi t 8, Chi t 8.0101, Chi t 9, Chi t 9.0101), Chlamys spp (Chl n 1), Chloephaga spp (Chl pi 1) Chortoglyphus spp (Cho a 10), Chrysomela spp (Chr tr 7, Chr tr 7.0101), Cicer spp (Cic a 2S アルブミン, Cic aアルブミン), Cichorium spp (Cic i 1), Cimex spp (Cim Iニトロフォリン), Citrus spp (Cit 11, Cit I 3, Cit I 3.0101), Citrullus spp (Cit la 2, Cit la MDH, Cit la TPI), Citrus spp (Cit r 3, Cit r 3.0101, Cit s 1, Cit s 1.0101, Cit s 2, Cit s 2.0101, Cit s 3, Cit s 3.0101, Cit s 3.0102, Cit s IFR), Cladosporium spp (Cla c 14, Cla c 14.0101, Cla c 9, Cla c 9.0101, Cla h 1, Cla h 10, Cla h 10.0101, Cla h 12, Cla h 12.0101, Cla h 2, Cla h 2.0101, Cla h 42 kD, Cla h 5, Cla h 5.0101, Cla h 6, Cla h 6.0101, Cla h 7, Cla h 7.0101, Cla h 8, Cla h 8 CSP, Cla h 8.0101, Cla h 9, Cla h 9.0101, Cla h abH, Cla h GST, Cla h HCh1, Cla h HSP70, Cla h NTF2, Cla h TCTP), Clostridium spp (Clo hi collagenase, Clo t toxoid), Clupea spp (Clu h 1, Clu h 1.0101, Clu h 1.0201, Clu h 1.0301), Cocos spp (Coc n 2, Coc n 4, Coc n 5), Coccidioides spp (Coc po 8), Coffea spp (Cof a 1, Cof a 1.0101), Columba spp (Col I PSA), Coprinus spp (Cop c 1, Cop c 1.0101, Cop c 2, Cop c 2.0101, Cop c 3, Cop c 3.0101, Cop c 4, Cop c 5, Cop c 5.0101, Cop c 6, Cop c 7, Cop c 7.0101), Corylus spp (Cor a 1, Cor a 1.0101, Cor a 1.0102, Cor a 1.0103, Cor a 1.0104, Cor a 1.Cor a 0201, Cor a 1.0301, Cor a 1.0401, Cor a 1.0402, Cor a 1.0403, Cor a 1.0404, Cor a 10, Cor a 10.0101, Cor a 11, Cor a 11.0101, Cor a 12, Cor a 12.0101, Cor a 13, Cor a 13.0101, Cor a 14, Cor a 14.0101, Cor a 2, Cor a 2.0101, Cor a 2.0102, Cor a 8, Cor a 8.0101, Cor a 9, Cor a 9.0101), Corynebacterium spp. (Cor d toxoid), Corylus spp. (Cor he 1), Coryphaena spp. (Cor hi 1), Coriandrum spp. (Cor s 1, Cor s 11 kD, Cor s 2), Cotoneaster spp. (Cot I 3), Crangon spp. (Cra c 1, Cra c 1.0101, Cra c 2, Cra c 2.0101, Cra c 4, Cra c 4.0101, Cra c 5, Cra c 5.0101, Cra c 6, Cra c 6.0101, Cra c 8, Cra c 8.0101), Crassostrea spp. (Cra g 1), Cricetus spp. (Cri c HSA), Crivellia spp. (Cri pa 1), Crocus spp. (Cro s 1, Cro s 1.0101, Cro s 2, Cro s 2.0101, Cro s 3, Cro s 3.01, Cro s 3.02), Cryptomeria spp. (Cry j 1, Cry j 1.0101, Cry j 1.0102, Cry j 1.0103, Cry j 2, Cry j 2.0101, Cry j 2.0102, Cry j 3, Cry j 3.1, Cry j 3.2, Cry j 3.3, Cry j 3.4, Cry j 3.5, Cry j 3.6, Cry j 3.7, Cry j 3.8, Cry j 4, Cry j AP, Cry j chitinase, Cry j CPA9, Cry j IFR, Cry j LTP, Cry j P1-P2), Cryphonectria spp (Cry p AP), Ctenocephalides spp (Cte f 1, Cte f 1.0101, Cte f 2, Cte f 2.0101, Cte f 3, Cte f 3.0101). Species of Ctenopharyngodon (Ctenopharyngodon spp) (Cte id 1), species of Cucumis (Cucumis spp) (Cuc m 1, Cuc m1.0101, Cuc m 2, Cuc m 2.0101, Cuc m 3, Cuc m 3.0101, Cuc m Lec17, Cuc m MDH), species of Cucurbita (Cucurbita spp) (Cuc ma 18 kD, Cuc ma 2, Cuc p 2, Cuc p AscO), species of Cucumis (Cucumis spp) (Cuc s 2), species of Culicoides (Culicoides spp) (Cul n 1, Cul n 10, Cul n 11, Cul n 2, Cul n 3, Cul n 4, Cul n 5, Cul n 6, Cul n 7, Cul n 8, Cul n 9, Cul n HSP70), species of Culex (Culex spp) (Cul q 28 kD, Cul q 35 kD, Cul q 7, Cul q 7.0101, Cul q 7.0102), species of Culicoides (Culicoides spp) (Cul so 1), species of Cuminum (Cuminum spp) (Cum c 1, Cum c 2), species of Cupressus (Cupressus spp) (Cup a 1, Cup a 1.0101, Cup a 1.02, Cup a 2, Cup a 3, Cup a 4, Cup a 4.0101, Cups 1, Cups 1.0101, Cups 1.0102, Cup s 1.0103, Cup s 1.0104, Cup s 1.0105, Cup s 3, Cup s 3.0101, Cup s 3.0102, Cup s 3.0103, Cup s 8), species of Cochliobolus (Cochliobolus spp) (Cur 11, Cur 11.0101, Cur I 2, Cur I 2.0101, Cur I 3, Cur I 3.0101, Cur I 4, Cur I 4.0101, Cur I ADH, Cur I GST, Cur I MnSOD, Cur I Oryzin, Cur I Trx, Cur I ZPS1), Cyanochen spp (Cya cy 1), Cynoscion spp (Cyn ar 1), Cynosurus spp (Cyn cr 1, Cyn cr 5), Cynodon spp (Cyn d 1, Cyn d 1.0101, Cyn d 1.0102, Cyn d 1.0103, Cyn d 1.0104, Cyn d 1.0105, Cyn d 1.0106, Cyn d 1.0107, Cyn d 1.0201, Cyn d 1.0202, Cyn d 1.0203, Cyn d 1.0204, Cyn d 10, Cyn d 11, Cyn d 12, Cyn d 12.0101, Cyn d 13, Cyn d 15, Cyn d 15.0101, Cyn d 2, Cyn d 22, Cyn d 22.0101, Cyn d 23, Cyn d 23.0101, Cyn d 24, Cyn d 2,4.0101, Cyn d 4, Cyn d 5, Cyn d 6, Cyn d 7, Cyn d 7.0101), Cynoscion spp (Cyn ne 1), Cynomys spp (Cyn sp Lipocalin), Cyprinus spp (Cyp c 1, Cyp c 1.01, Cyp c 1.02), Daboia spp (Dab ru 1), Dactylis spp (Dac g 1, Dac g 1.01, Dac g 1.0101, Dac g 1.02, Dac g 12, Dac g 13, Dac g 2, Dac g 2.0101, Dac g 3, Dac g 3.0101, Dac g 4, Dac g 4.0101, Dac g 5, Dac g 5. It should be noted that there seem to be some incomplete or unclear parts in the original text (such as "Cyn d 2,4.0101" which might be a formatting error). This translation is done based on the best understanding of the existing content.0101, Dac g 7), Dama spp (Dam d CSA), Danio spp (Dan re 1, Dan re 2, Dan re Alpha 2l, Dan re CK), Dasyatis spp (Das ak 1, Das am 1, Das sa 1), Daucus spp (Dau c 1, Dau c 1.0101, Dau c 1.0102, Dau c 1.0103, Dau c 1.0104, Dau c 1.0105, Dau c 1.0201, Dau c 1.0301, Dau c 3, Dau c 4, Dau c 4.0101, Dau c CyP), Decapterus sp. spp) (Dec ru 1), Dendronephthya spp) (Den n 1, Den n 1.0101), Dermatophagoides spp) (Der f 1, Der f 1.0101, Der f 1.0102, Der f 1.0103, Der f 1.0104, Der f 1.0105, Der f 1.0106, Der f 1.0107, Der f 1.0108, Der f 1.0109, Der f 1.0110, Der f 10, Der f 10.0101, Der f 10.0102, Der f 11, Der f 11.0101, Der f 13, Der f 13.0101, Der f 14, Der f 14.0101, Der f 15, Der f 15.0101, Der f 16, Der f 16.0101, Der f 17, Der f 17.0101, Der f 18, Der f 18.0101, Der f 2, Der f 2.0101, Der f 2.0102, Der f 2.0103, Der f 2.0104, Der f 2.0105, Der f 2.0106, Der f 2.0107, Der f 2.0108, Der f 2.0109, Der f 2.0110, Der f 2.0111, Der f 2.0112, Der f 2.0113, Der f 2.0114, Der f 2.0115, Der f 2.0116, Der f 2.0117, Der f 20, Der f 21, Der f 22, Der f 22.0101, Der f 3, Der f 3.0101, Der f 4, Der f 5, Der f 6, Der f 6.0101, Der f 7, Der f 7.0101, Der f 8, Der f 9, Der f HSP70), Dermanyssus spp (Der g 10, Der g 10.0101), Dermatophagoides spp (Der m 1, Der m 1.0101, Der p 1, Der p 1.0101, Der p 1.0102, Der p 1.0103, Der p 1.0104, Der p 1.0105, Der p 1.0106, Der p 1.0107, Der p 1.0108, Der p 1.0109, Der p 1.0110, Der p 1.0111, Der p 1.0112, Der p 1.0113, Der p 1.0114, Der p 1.0115, Der p 1.0116, Der p 1.0117, Der p 1.0118, Der p 1.0119, Der p 1.0120, Der p 1.0121, Der p 1.0122, Der p 1.0123, Der p 1.0124, Der p 10, Der p 10.0101, Der p 10.0102, Der p 10.0103, Der p 11, Der p 11.0101, Der p 13, Der p 14, Der p 14.0101, Der p 15, Der p 18, Der p 2, Der p 2.0101, Der p 2.0102, Der p 2.0103, Der p 2.0104, Der p 2.0105, Der p 2.0106, Der p 2.0107, Der p 2.0108, Der p 2.0109, Der p 2.0110, Der p 2.0111, Der p 2.0112, Der p 2. It should be noted that this text seems to be rather jumbled and may require further clarification or correction in its original form for a more meaningful translation and understanding.0113, Der p 2.0114, Der p 2.0115, Der p 20, Der p 20.0101, Der p 21, Der p 21.0101, Der p 23, Der p 23.0101, Der p 3, Der p 3.0101, Der p 4, Der p 4.0101, Der p 5, Der p 5.0101, Der p 5.0102, Der p 6, Der p 6.0101, Der p 7, Der p 7.0101, Der p 8, Der p 8.0101, Der p 9, Der p 9.0101, Der p 9.0102, Der p P1-P2, Der p P2-P1, Der s 1, Der s 2, Der s 3), Dianthus spp. (Dia c RIP), Dicranopteris spp. (Dic I 2S albumin), Diospyros spp. (Dio k 17 kD, Dio k 4, Dio k IFR), Dioscorea spp. (Dio p TSP), Diplodus spp. (Dip ho 1), Distichlis spp. (Dis s 1, Dis s 7), Ditrema spp. (Dit to 1), Dolichovespula spp. (Dol a 1, Dol a 2, Dol a 5, Dol a 5.0101), Dolichos spp. (Dol b agglutinin), Dolichovespula spp. (Dol m 1, Dol m 1.0101, Dol m 1.02, Dol m 2, Dol m 2.0101, Dol m 5, Dol m 5.0101, Dol m 5.02), Drosophila spp. (Dro an 7, Dro an 7.0101, Dro er 7, Dro er 7.0101, Dro er 7.0102, Dro gr 7, Dro gr 7.0101, Dro gr 7.0102, Dro m 7, Dro m 7.0101, Dro m 7.0102, Dro m 7.0103, Dro m 7.0104, Dro m 7.0105, Dro m 7.0106, Dro m 7.0107, Dro m 7.0108, Dro m 7.0109, Dro m 7.0110, Dro m 7.0111, Dro m 7.0112, Dro m 7.0113, Dro m 9, Dro m MnSOD, Dro mo 7, Dro mo 7.0101, Dro pp 7, Dro pp 7.0101, Dro se 7, Dro se 7.0101, Dro si 7, Dro si 7.0101, Dro si 7.0102, Dro vi 7, Dro vi 7.0101, Dro wi 7, Dro wi 7.0101, Dro y 7, Dro y 7.0101, Dro y 7.0102, Dro y 7.0103), Echium spp (Ech p Cytochrome C), Elaeis spp (Ela g 2, Ela g Bd31 kD), Elops spp (Elo sa 1), Embellisia spp (Emb a 1, Emb i 1, Emb nz 1, Emb t 1), Engraulis spp (Eng e 1), Enteroctopus spp (Ent d 1), Epinephelus spp (Epi bl 1, Epi co 1, Epi fl 1, Epi mc 1, Epi mo 1), Epicoccum spp (Epi p 1, Epi p 1.0101, Epi p 12 kD, Epi p GST), Epinephelus spp (Epi po 1, Epi un 1), Equisetum spp (Equ a 17 kD), Equus spp (Equ as 4, Equ as DSA, Equ bu 4, Equ c 1, Equ c 1.0101, Equ c 2, Equ c 2.0101, Equ c 2.0102, Equ c 3, Equ c 3.0101, Equ c 4, Equ c 4.0101, Equ c 5, Equ c 5.0101, Equ c ALA, Equ c BLG, Equ c casein, Equ c casein beta, Equ c casein kappa, Equ c PRVB, Equ he 4, Equ z ZSA), Erimacrus spp. (En i 1, En i 1.0101, Eri i 1.0102), Eriocheir spp. (Eri s 1, Eri s 1.0101, En s 2), Erwinia spp. (Erw ch asparaginase), Escherichia spp. (Esc c asparaginase, Esc c beta GAL), Esox spp. (Eso 11), Euphausia spp. (Eup p 1, Eup p 1.0101), Euphasia spp. (Eup s 1, Eup s 1.0101), Euroglyphus spp. (Eur m 1, Eur m 1.0101, Eur m 1.0102, Eur m 1.0103, Eur m 10, Eur m 14, Eur m 14.0101, Eur m 2, Eur m 2.0101, Eur m 2.0102, Eur m 3, Eur m 3.0101, Eur m 4, Eur m 4.0101), Evynnis spp (Evy j 1), Fagopyrum spp (Fag e 1, Fag e 1.0101, Fag e 10 kD, Fag e 19 kD, Fag e 2, Fag e 2.0101, Fag e TI), Fagus spp (Fag s 1, Fag s 1.0101, Fag s 2, Fag s 4), Fagopyrum spp (Fag t 1, Fag t 10 kD, Fag t 2, Fag t 2.Felis spp (Fel d 1, Fel d 1.0101, Fel d 2, Fel d 2.0101, Fel d 3, Fel d 3.0101, Fel d 4, Fel d 4.0101, Fel d 5, Fel d 5.0101, Fel d 6, Fel d 6.0101, Fel d 7, Fel d 7.0101, Fel d 8, Fel d 8.0101, Fel d IgG), Fenneropenaeus spp (Fen c 1, Fen c 2, Fen me 1, Fen me 1.0101), Festuca spp (Fes e 1, Fes e 13, Fes e 4, Fes e 5, Fes e 7, Fes p 1, Fes p 13, Fes p 4, Fes p 4.0101, Fes p 5, Fes r 1, Fes r 5), Ficus spp. (Fic c 17 kD, Fic c 4, Fic c ficin), Fennel spp. (Foeniculum spp.) (Foe v 1, Foe v 2), Forsythia spp. (For s 1), Forcipomyia spp. (Fort 1, Fort 1.0101, Fort 2, Fort 2.0101, Fort 7, Fort FPA, Fort myosin, Fort TPI), Fragaria spp. (Fra a 1, Fra a 1.0101, Fra a 3, Fra a 3.0101, Fra a 3.0102, Fra a 3.0201, Fra a 3.0202, Fra a 3.0203, Fra a 3.0204, Fra a 3.0301, Fra a 4, Fra a 4.0101, Fra c 1), Fraxinus sp. spp) (Fra e 1, Fra e 1.0101, Fra e 1.0102, Fra e 1.0201, Fra e 12, Fra e 2, Fra e 3, Fra e 9), Fragaria spp. (Fra v 1), Fusarium spp. (Fus c 1, Fus c 1.0101, Fus c 2, Fus c 2.0101, Fus c 3, Fus s 1, Fus s 45 kD, Fus sp lipase), Gadus spp. (Gad c 1, Gad c 1.0101, Gad c APDH, Gad m 1, Gad m 1.0101, Gad m 1.0102, Gad m 1.0201, Gad m 1.0202, Gad m 45 kD, Gad m gelatin, Gad ma 1), Gallus spp (Gal d 1, Gal d 1.0101, Gal d 2, Gal d 2.0101, Gal d 3, Gal d 3.0101, Gal d 4, Gal d 4.0101, Gal d 5, Gal d 5.0101, Gal d 6, Gal d 6.0101, Gal d Apo I, Gal d Apo VI, Gal d GPI, Gal d HG, Gal d IgY, Gal d L-PGDS, Gal d ovomucin, Gal d phosvitin, Gal d PRVB, Gal la 4), Galleria spp (Gal m 18 kD, Gal m 24 kD), Gallus spp. spp) (Gal so 4), Gammarus spp (Gam s TM), Gelonium spp (Gel m RIP), Geothelphusa spp (Geo de 1), Glossina spp (Glo m 5, Glo m 5.0101, Glo m 7, Glo m 7.0101, Glo m 7.0102, Glo m 7.0103), soybean species (Glycine spp) (Gly a Bd30K, Gly ar Bd30K, Gly ca Bd30K, Gly cl Bd30K, Gly cu Bd30K, Gly cy Bd30K), dust mite genus (Glycyphagus spp) (Gly d 10, Gly d 10.0101, Gly d 13, Gly d 2, Gly d 2.0101, Gly d 2.0201, Gly d 2.03, Gly d 2 / Lep d 2 L1, Gly d 2 / Lep d 2 L2, Gly d 2 / Lep d 2 L3, Gly d 2 / Lep d 2 L4, Gly d 2 / Lep d 2 R1, Gly d 2 / Lep d 2 R2, Gly d 2 / Lep d 2 R3, Gly d 2 / Lep d 2 R4, Gly d 2 / Lep d 2 R5, Gly d 20, Gly d 3, Gly d 5, Gly d 5.01, Gly d 5.02, Gly d 7, Gly d 8), soybean species (Glycine spp) (Gly f Bd30K, Gly I Bd30K, Gly m 1, Gly m 1.0101, Gly m 1.0102, Gly m 2, Gly m 2.0101, Gly m 2S albumin, Gly m 3, Gly m 3.0101, Gly m 3.0102, Gly m 39 kD, Gly m 4, Gly m 4.0101, Gly m 5, Gly m 5.0101, Gly m 5.0201, Gly m 5.0301, Gly m 5.0302, Gly m 50 kD, Gly m 6, Gly m 6.0101, Gly m 6.0201, Gly m 6.0301, Gly m 6.0401, Gly m 6.0501, Gly m 68 kD, Gly m agglutinin, Gly m Bd28K, Gly m Bd30K, Gly m Bd60K, Gly m CPI, Gly m E. AP, Gly m TI, Gly mi Bd30K, Gly s Bd30K, Gly t Bd30K, Gly to Bd30K)、 Gossypium spp. (Gos h vicilin), Haemophilus spp. (Hae in P6), Haemaphysalis spp. (Hae 17, Hae 1 7.0101, Hae q 7, Hae q 7.0101), Haliotis spp. (Hal a 1, Hal d 1, Hal di 1, Hal di PM, Hal m 1, Hal m 1.0101, Hal r 1, Hal r 49 kD, Hal ru 1), Harmonia spp. (Har a 1, Har a 1.0101, Har a 2, Har a 2.0101), Harpegnathos spp. (Har sa 7, Har sa 7.0101, Har sa 7.0102), Helianthus spp. (Hel a 1, Hel a 1.0101, Hel a 2, Hel a 2.0101, Hel a 2S albumin, Hel a 3, Hel a 3.0101, Hel a 4), Helix spp. (Hel ap 1, Hel as 1, Hel as 1.0101), Heligmosomoides spp. (Hel p 3, Hel p 3.0101), Helianthus spp. (Hel to 1), Hemanthias spp. (Hem le 1), Hemifusus spp. (Hem t 1), Heterodera spp. (Het g 3, Het g 3.0101), Hevea spp. (Hey b 1, Hey b 1.0101, Hey b 10, Hey b 10.0101, Hey b 10.0102, Hey b 10.0103, Hey b 11, Hey b 11.0101, Hey b 11.0102, Hey b 12, Hey b 12.0101, Hey b 13, Hey b 13.0101, Hey b 14, Hey b 14.0101, Hey b 2, Hey b 2.0101, Hey b 3, Hey b 3.0101, Hey b 4, Hey b 4.0101, Hey b 5, Hey b 5.0101, Hey b 6, Hey b 6.01, Hey b 6.02, Hey b 6.0202, Hey b 6.03, Hey b 7, Hey b 7.01, Hey b 7.02, Hey b 7.D2, Hey b 7.S2, Hey b 8, Hey b 8.0101, Hey b 8.0102, Hey b 8.0201, Hey b 8.0202, Hey b 8.0203, Hey b 8.0204, Hey b 9, Hey b 9.0101, Hey b citrate binding protein, Hey b GAPDH, Hey b HSP80, Hey b IFR, Hey b proteasome subunit, Hey b rotamase, Hey b SPI, Hey b Trx, Hey b UDPGP), Hexagrammos spp. (Hex of 1), Hippoglossus spp. (Hip h 1), Hippoglossoides spp. (Hip pl 1), Hippoglossus spp. (Hip st 1), Hirudo spp. (Hir me hirudin), Holcus spp. (Hol 1 1, Hol 1 1.0101, Hol 1 1.0102, Hol 1 2, Hol 1 4, Hol 1 5, Hol 1 5.0101, Hol 1 5.0201), Holocnemus spp. (Hol pl 9, Hol pl hemocyanin), Homarus spp. (Hom a 1, Hom a 1.0101, Hom a 1.0102, Hom a 1.0103, Hom a 3, Hom a 3.0101, Hom a 4, Hom a 6, Hom a 6.0101, Hom g 1, Hom g 2), Homo spp. (Hom s 1, Hom s 1.0101, Hom s 2, Hom s 2.0101, Hom s 3, Hom s 3.0101, Hom s 4, Hom s 4.0101, Hom s 5, Hom s 5.0101, Hom's AAT, Hom's ACTH, Hom's Adalimumab, Hom's ALA, Hom's alpha-actin, Hom's alpha-galactosidase, Hom's APDH, Hom's arylsulfatase B, Hom's casein, Hom's CyP A, Hom's CyP B, Hom's CyP C, Hom's DSF70, Hom's DSG3, Hom's eIF6, Hom's etanercept, Hom's factor IX, Hom's factor VII, Hom's factor VIII, Hom's G-CSF, Hom's glucocerebrosidase, Hom's glucosidase, Hom's HLA-DR-alpha, Hom's HSA, Hom's iduronidase, Hom's idursulfase Hom s IgA, Hom s Insulin, Hom s Lactoferrin, Hom s Laminin-gamma_2, Hom s MnSOD, Hom s Oxytocin, Hom s P2, Hom s Phosvitin, Hom s Profilin, Hom s PSA, Hom s RP1, Hom s TCTP, Hom s TL, Hom s TPA, Hom s TPO, Hom s Transaldolase, Hom s Trx, Hom s Tubulin-alpha, Hom s / Mus m Basiliximab, Hom s / Mus m Cetuximab, Hom s / Mus m Cetuximab (Gal-Gal), Hom s / Mus m Infliximab, Hom s / Mus m Natalizumab, Hom s / Mus m Omalizumab, Hom s / Mus m palivizumab, Hom s / Mus m rituximab, Hom s / Mus m tocilizumab, Hom s / Mus m trastuzumab), Hoplostethus spp (Hop a 1), Hordeum spp (Hor v 1, Hor v 12, Hor v 12.0101, Hor v 13, Hor v 14, Hor v 15, Hor v 15.0101, Hor v 16, Hor v 16.0101, Hor v 17, Hor v 17.0101, Hor v 18 kD, Hor v 2, Hor v 21, Hor v 21.0101, Hor v 28, Hor v 33, Hor v 4, Hor v 5, Hor v 5.0101, Hor v BDAI, Hor v BTI), Humicola spp. (Hum in cellulase), Humulus spp. (Hum j 1, Hum j 1.0101, Hum j 10 kD, Hum j 2), Huso spp. (Hus h 1), Hylocereus spp. (Hyl un LTP), Hymenocephalus spp (Hym st 1), Hyperoglyphe spp (Hyp by 1), Hypophthalmichthys spp (Hyp mo 1), Hypophthalmichthy spp (Hyp no 1), Ictalurus spp (Ict fu 1, Ict p 1), Imperata spp (Imp c 4, Imp c 5, Imp c VIIIe1), Ixodes spp (Ixo r 2, Ixo sc 7, Ixo sc 7.0101), Jasus spp (Jas la 1, Jas la 1.0101, Jas la 1.0102), Juglans spp (Jug ca 1, Jug ca 2, Jug ci 1, Jug ci 2, Jug n 1, Jug n 1.0101, Jug n 2, Jug n 2.0101, Jug r 1, Jug r 1.0101, Jug r 2, Jug r 2.0101, Jug r 3, Jug r 3.0101, Jug r 4, Jug r 4.0101, Jug r 5), Juniperus spp (Jun a 1, Jun a 1.0101, Jun a 1.0102, Jun a 2, Jun a 2.0101, Jun a 3, Jun a 3. 0101, Jun c 1, Jun o 1, Jun o 4, Jun o 4. 0101, Jun r 3, Jun r 3.1, Jun r 3.2, Jun v 1, Jun v 1. 0101, Jun v 1. 0102, Jun v 3, Jun v 3. 0101, Jun v 3. 0102, Jun v 4), Katsuwonus spp (Kat p 1), Kyphosus spp (Kyp se 1), Lachnolaimus spp (Lac ma 1), Lachesis spp (Lac mu 1), Lactuca spp (Lac s 1, Lac s 1.0101), Lagocephalus spp. (Lag la 1), Larus spp. (Lar a 1, Lar a 2, Lar a 3), Larimichthys spp. (Lar po 1), Lates spp. (Lat c 1), Lateolabrax spp. (Lat ja 1), Lathyrus spp. (Lat oc agglutinin), Leiostomus spp. (Lei xa 1), Lens spp. (Len c 1, Len c 1.0101, Len c 1.0102, Len c 1.0103, Len c 2, Len c 2.0101, Len c 3, Len c 3.0101, Len c agglutinin), Leopardus spp (Leo p 1), Lepidoglyphus spp (Lep d 10, Lep d 10.0101, Lep d 12, Lep d 13, Lep d 13.0101, Lep d 2, Lep d 2.0101, Lep d 2.0102, Lep d 2.0201, Lep d 2.0202, Lep d 3, Lep d 39 kD, Lep d 5, Lep d 5.0101, Lep d 5.0102, Lep d 5.0103, Lep d 7, Lep d 7.0101, Lep d 8, Lep d alpha tubulin), Lepomis spp. (Lep gi 1), Leptomelanosoma spp. (Lep i 1), Lepomis spp. (Lep ma 1), Lepisma spp. (Lep s 1, Lep s 1.0101, Lep s 1.0102), Lepeophtheirus spp. (Lep sa 1, Lep sa 1.0101, Lep sa 1.0102, Lep sa 1.0103), Leptailurus spp. (Lep se 1), Lepidorhombus spp. (Lep w 1, Lep w 1.0101), Lethocerus spp. (Let in 7, Let in 7.0101, Let in 7.0102), Leuciscus spp. (Leu ce 1), Lewia spp. (Lew in 1), Ligustrum spp. (Lig v 1, Lig v 1.0101, Lig v 1.0102, Lig v 2), Lilium spp. (Lil 12, Lil I PG), Limanda spp. (Lim fe 1), Limnonectes spp. (Lim m 1), Limulus spp. (Lim p 1, Lim p 1.0101, Lim p 2, Lim p LPA), Liposcelis spp. (Lip b 1, Lip b 1.0101), Litchi spp. (Lit c 1, Lit c 1.0101, Lit c IFR, Lit c TPI), Lithobates spp. (Lit ca 1), Litopenaeus spp. (Lit se 1, Lit v 1, Lit v 1.0101, Lit v 2, Lit v 2.0101, Lit v 3, Lit v 3.0101, Lit v 4, Lit v 4.0101), Filiaria spp (Loa lo 3, Loa lo 3.0101), Lobotes spp (Lob su 1), Locusta spp (Loc m 7, Loc m 7.0101), Loligo spp (Lol b 1, Lol e 1), Lolium spp (Lol m 2, Lol m 5, Lol p 1, Lol p 1.0101, Lol p 1.0102, Lol p 1.0103, Lol p 10, Lol p 11, Lol p 11.0101, Lol p 12, Lol p 13, Lol p 2, Lol p 2.0101, Lol p 3, Lol p 3.0101, Lol p 4, Lol p 4.0101, Lol p 5, Lol p 5.0101, Lol p 5.0102, Lol p 7, Lol p CyP, Lol p FT, Lol p legumin), Lonomia spp (Lon o 7, Lon o 7.0101), Lophodytes spp (Lop cu 1), Lophonetta spp (Lop sp 1), Lupinus spp (Lup a 1, Lup a Alpha_conglutin, Lup a Delta_conglutin, Lup a Gamma_conglutin, Lup an 1, Lup an 1.0101, Lup an alpha_conglutin, Lup an delta_conglutin, Lup an gamma_conglutin, Lup 117 kD), Lutjanus spp. (Lut a 1, Lut c 1, Lut cy 1, Lut gr 1, Lut gu 1, Lut jo 1), Lutraria spp. (Lut p 1), Lutjanus spp. (Lut pu 1, Lut sy 1), Lycopersicon spp. (Lyc e 1, Lyc e 1.0101, Lyc e 11S globulin, Lyc e 2, Lyc e 2.0101, Lyc e 2.0102, Lyc e 3, Lyc e 3.0101, Lyc e 4, Lyc e 4.0101, Lyc e ARP60S, Lyc e chitinase, Lyc e glucanase, Lyc e peroxidase, Lyc e PG, Lyc e PME, Lyc e PR23, Lyc e vicilin), Maconellicoccus spp (Mac h 7, Mac h 7.0101), Macruronus spp (Mac ma 1, Mac n 1), Maclura spp (Mac po 17 kD), Macrobrachium spp (Mac ro 1, Mac ro 1.0101, Mac ro hemocyanin), Macropus spp (Marr s gelatin), Malus spp (Mal d 1, Mal d 1.0101, Mal d 1.0102, Mal d 1.0103, Mal d 1.0104, Mal d 1.0105, Mal d 1.0106, Mal d 1.0107, Mal d 1.0108, Mal d 1.0109, Mal d 1.0201, Mal d 1.0202, Mal d 1.0203, Mal d 1.0204, Mal d 1.0205, Mal d 1.0206, Mal d 1.0207, Mal d 1.0208, Mal d 1.0301, Mal d 1.0302, Mal d 1.0303, Mal d 1.0304, Mal d 1.0401, Mal d 1.0402, Mal d 1.0403, Mal d 2, Mal d 2.0101, Mal d 3, Mal d 3.0101, Mal d 3.0102, Mal d 3.0201, Mal d 3.0202, Mal d 3.0203, Mal d 4, Mal d 4.0101, Mal d 4.0102, Mal d 4.0201, Mal d 4.0202, Mal d 4.0301, Mal d 4.0302), Malpighia spp (Mal g 4, Mal g hevein), Malus spp. (Mal p 1), Malassezia spp. (Mala f 2, Mala f 2.0101, Mala f 3, Mala f 3.0101, Mala f 4, Mala f 4.0101, Mala g 10, Mala s 1, Mala s 1.0101, Mala s 10, Mala s 10.0101, Mala s 11, Mala s 11.0101, Mala s 12, Mala s 12.0101, Mala s 13, Mala s 13.0101, Mala s 5, Mala s 5.0101, Mala s 6, Mala s 6.0101, Mala s 7, Mala s 7.0101, Mala s 8, Mala s 8.0101, Mala s 9, Mala s 9.0101), Manihot spp. (Man e 5, Man e 5.0101, Man e FPA, Man e GAPDH), Mangifera spp. (Man i 1, Man i 14 kD, Man i 2, Man i 3, Man i 3.01, Man i 3.02, Man i chitinase), Marsupenaeus spp. (Mar j 1, Mar j 1.0101, Mar j 2, Mar j 4), Matricaria spp (Mat c 17 kD), Mecopoda spp (Mec e 7), Megalobrama spp (Meg am 2, Meg am CK), Megathura spp (Meg c hemocyanin), Megalops spp (Meg sp 1), Melanogrammus spp (Mel a 1),. Meleagris spp. (Mel g 1, Mel g 2, Mel g 3, Mel g PRVB, Mel g TSA), Melicertus spp. (Mel 11), Menticirrhus spp. (Men am 1), Mercurialis spp. (Mer a 1, Mer a 1.0101), Merluccius spp. (Mer ap 1, Mer au 1, Mer bi 1, Mer ca 1, Mer ga 1, Mer hu 1), Merlangius spp. (Mer me 1), Merluccius spp. (Mer mr 1, Mer pa 1, Mer po 1, Mer pr 1, Mer se 1), Meriones spp (Mer un 23 kD), Metarhizium spp (Met a 30), Metapenaeopsis spp (Met ba 1), Metapenaeus spp (Mete 1, Mete 1.0101, Met e 2), Metasequoia spp (Met gl 2), Metapenaeus spp (Met j 1, Met j 2), Metanephrops spp (Met ja 1), Metapenaeopsis spp (Met la 1), Metapenaeopsis spp (Met la 1) spp) (Met t 2), Micromesistius spp. (Mic po 1), Micropogonias spp. (Mic un 1), Mimachlamys spp. (Mim n 1), Momordica spp. (Mom c RIP), Morus spp. (Mor a 17 kD, Mor a 4), Morone spp. (Mor am 1), Morus spp. (Mor n 3, Mor n 3.0101), Morone spp. (Mor sa 1, Mor sc 1), Mugil spp. (Mug c 1), Muraenolepis spp. (Mur mi 1), Musa spp. (Mus a 1, Mus a 1.0101, Mus a 2, Mus a 2.0101, Mus a 3, Mus a 3.0101, Mus a 4, Mus a 4.0101, Mus a 5, Mus a 5.0101, Mus a 5.0102), Mus spp. (Mus m 1, Mus m 1.0101, Mus m 1.0102, Mus m 2, Mus m gelatin, Mus m IgG, Mus m MSA, Mus m Muromonab, Mus m phosvitin), Mustela spp. (Mus p 17 kD), Musa spp. (Mus xp 1, Mus xp 2, Mus xp 5), Mycteroperca spp. (Myc bo 1, Myc mi 1, Myc ph 1), Myceliophthora spp. (Myc sp laccase), Myrmecia spp. (Myr p 1, Myr p 1.0101, Myr p 2, Myr p 2.0101, Myr p 2.0102, Myr p 3, Myr p 3.0101), Mytilus spp. (Myt e 1, Myt g 1, Myt g PM), Myzus spp (Myz p 7, Myz p 7.0101), Nemorhedus spp (Nae go Hya), Necator spp (Nec a calreticulin), Nemipterus spp (Nem vi 1), Neosartorya spp (Neo fi 1, Neo fi 22), Neochen spp (Neo ju 1), Neoscona spp (Neo n 7, Neo n 7.0101), Nephelium spp. (Nep I GAPDH), Nephrops spp. (Nep n 1, Nep n DF9), Neptunea spp. (Nep po 1, Nep po 1.0101), Nicotiana spp. (Nic t 8, Nic t osmotin, Nic t bilin), Nimbya spp. (Nim c 1, Nim s 1), Nippostrongylus spp. (Nip b Ag1), Nycticebus spp. (Nyc c 1), Octopus spp. (Oct f 1, Oct 11, Oct v 1, Oct v 1.0101, Oct v PM), Ocyurus spp (Ocy ch 1), Olea spp (Ole e 1, Ole e 1.0101, Ole e 1.0102, Ole e 1.0103, Ole e 1.0104, Ole e 1.0105, Ole e 1.0106, Ole e 1.0107, Ole e 10, Ole e 10.0101, Ole e 11, Ole e 11.0101, Ole e 11.0102, Ole e 12, Ole e 13, Ole e 2, Ole e 2.0101, Ole e 3, Ole e 3.0101, Ole e 36 kD, Ole e 4, Ole e 4.0101, Ole e 5, Ole e 5.0101, Ole e 6, Ole e 6.0101, Ole e 7, Ole e 7.0101, Ole e 8, Ole e 8.0101, Ole e 9, Ole e 9.0101), neon flying squid (Ommastrephes spp) (Omm b 1, Omm b 1.0101), Pacific salmon (Oncorhynchus spp) (Onc ke 1, Onc ke 18 kD, Onc ke alpha 2I, Onc ke vitellogenin, Onc m 1, Onc m 1.0101, Onc m 1.0201, Onc m alpha 2I, Onc m protamine, Onc m vitellogenin, Onc ma 1, Onc ma FPA, Onc ma FSA, Onc ma TPI, Onc n 1), Onchocerca spp. (Onc o 3, Onc o 3.0101), Oncorhynchus spp. (Onc is 1), Onchocerca spp. (Onc v 3, Onc v 3.0101), Oratosquilla spp. (Ora o 1, Ora o 1.0101), Oreochromis spp. (Ore a 1, Ore mo 1, Ore mo 2, Ore mo FPA, Ore mo SCAF7145, Ore ni 1, Ory ni 18 kD, Ory ni 45 kD), house dust mite species (Ornithonyssus spp) (Orn sy 10, Orn sy 10.0101, Orn sy 10.0102), Oryctolagus spp (Ory c 1, Ory c 1.0101, Ory c 2, Ory c casein, Ory c phosvitin, Ory c RSA), rice species (Oryza spp) (Ory s 1, Ory s 1.0101, Ory s 11, Ory s 12, Ory s 12.0101, Ory s 13, Ory s 14, Ory s 17 kD, Ory s 19 kD, Ory s 2, Ory s 23, Ory s 3, Ory s 7, Ory s akTI, Ory s GLP52, Ory s GLP63, Ory s glyoxalase I, Ory s NRA), Ostrya spp. (Ost c 1, Ost c 1.0101), Ovis spp. (Ovi a ALA, Ovi a BLG, Ovi a casein, Ovi a casein alpha S1, Ovi a casein alpha S2, Ovi a casein beta, Ovi a casein kappa, Ovi a phosvitin, Ovi a SSA), Pachycondyla spp. (Pac c 3), Pagrus spp. (Pag m 1, Pag pa 1), Pampus spp. (Pam ar 1, Pam c 1), Pandalus spp. (Pan b 1, Pan b 1.0101), Pangasius spp. (Pan bo 1), Pandalus spp. spp) (Pan e 1, Pan e 1.0101, Pan e 4), Panulirus spp) (Pan h 1, Pan hy 1), Pangasius spp) (Pan hy 18 kD, Pan hy 45 kD), Panulirus spp) (Pan j 1), Panthera spp) (Pan 11, Pan o 1, Pan p 1), Panulirus spp) (Pan s 1, Pan s 1.0101), Panthera spp) (Pan t 1), Pan spp) (Pan tr TCTP), Papaver spp) (Pap s 17 kD, Pap s 2, Pap s 34 kD), swallowtail butterfly species (Papilio spp) (Pap xu 7, Pap xu 7.0101, Pap xu 7.0102), flounder species (Paralichthys spp) (Par a 1), Asian catfish species (Parasilurus spp) (Par as 1, Par c 1), red king crab species (Paralithodes spp) (Par c 1.0101, Par c 1.0102, Par f 1), Parthenium spp (Par h 1), Parietaria spp (Par j 1, Par j 1.0101, Par j 1.0102, Par j 1.0103, Par j 1.0201, Par j 2, Par j 2.0101, Par j 2.0102, Par j 3, Par j 3.0101, Par j 3.0102, Par j 4, Par j 4.0101, Par j J1-J2), Paralichthys spp (Par le 1), Parietaria spp (Par m 1, Par o 1, Par o 1.0101), Paralichthys spp. (Par of 1, Par of alpha 2I), Parahucho spp. (Par pe vitellogenin), Passiflora spp. (Pas e chitinase, Pas e hevein), Paspalum spp. (Pas n 1, Pas n 1.0101, Pas n 13), Patinopecten spp. (Pat y 1), Pediculus spp. (Ped h 7, Ped h 7.0101), Penaeus spp. (Pen a 1, Pen a 1.0101, Pen a 1.0102, Pen a 1.0102 (103-117), Pen a 1.0102 (109-123), Pen a 1.0102 (1-15), Pen a 1.0102 (115-129), Pen a 1.0102 (121-135), Pen a 1.0102 (127-141), Pen a 1.0102 (13-27), Pen a 1.0102 (133-147), Pen a 1.0102 (139-153), Pen a 1.0102 (145-159)), Farfantepenaeus spp. (Pen a 1.0102 (151-165)), Penaeus spp. (Pen a 1.0102 (157-171), Pen a 1.0102 (163-177), Pen a 1.0102 (169-183), Pen a 1.0102 (175-189), Pen a 1.0102 (181-195), Pen a 1.0102 (187-201), Pen a 1.0102 (193-207), Pen a 1.0102 (19-33), Pen a 1.0102 (199-213), Pen a 1.0102 (205-219), Pen a 1.0102 (211-225), Pen a 1.0102 (217-231), Pen a 1.0102 (223-237), Pen a 1.0102 (229-243)), Farfantepenaeus spp. (Pen a 1.0102 (235-249)), Penaeus spp. (Pen a 1.0102 (241-255), Pen a 1.0102 (247-261), Pen a 1.0102 (253-267), Pen a 1.0102 (25-39), Pen a 1.0102 (259-273), Pen a 1.0102 (265-279), Pen a 1.0102 (270-284), Pen a 1.0102 (31-45), Pen a 1.0102 (37-51), Pen a 1.0102 (43-57), Pen a 1.0102 (49-63)), Farfantepenaeus spp. (Pen a 1.0102 (55-69)), Penaeus spp. (Pen a 1.0102 (61-75), Pen a 1.0102 (67-81), Pen a 1.0102 (7-21), Pen a 1.0102 (73-87), Pen a 1.0102 (79-93), Pen a 1.0102 (85-99), Pen a 1.0102 (91-105), Pen a 1.0102 (97-111), Pen a 1.0103), Penicillium spp. (Pen b 13, Pen b 13.0101, Pen b 26, Pen b 26.0101, Pen c 1, Pen c 13, Pen c 13.0101, Pen c 18, Pen c 19, Pen c 19.0101, Pen c 2, Pen c 22, Pen c 22.0101, Pen c 24, Pen c 24.0101, Pen c 3, Pen c 3.0101, Pen c 30, Pen c 30.0101, Pen c 32, Pen c 32.0101, Pen c MnSOD, Pen ch 13, Pen ch 13.0101, Pen ch 18, Pen ch 18.0101, Pen ch 20, Pen ch 20.0101, Pen ch 31, Pen ch 31.0101, Pen ch 33, Pen ch 33.0101, Pen ch 35, Pen ch 35.0101, Pen ch MnSOD), Penaeus spp (Pen i 1, Pen i 1.0101, Pen m 1, Pen m 1.0101, Pen m 1.0102, Pen m 2, Pen m 2.0101, Pen m 3, Pen m 3.0101, Pen m 4, Pen m 4.0101, Pen m 6, Pen m 6.0101), Penicillium spp (Pen o 18, Pen o 18.0101), Penaeus spp (Pena o 1, Pena o 1.0101), Periplaneta spp (Per a 1, Per a 1.0101, Per a 1.0102, Per a 1.0103, Per a 1.0104, Per a 1.0105, Per a 1.0201, Per a 10, Per a 10.0101, Per a 2, Per a 3, Per a 3.0101, Per a 3.0201, Per a 3.0202, Per a 3.0203, Per a 4, Per a 5, Per a 6, Per a 6.0101, Per a 7, Per a 7.0101, Per a 7.0102, Per a 7.0103, Per a 9, Per a 9.0101, for cathepsin, for FABP, for trypsin, for f 1, for f 7, for f 7.0101), mussel species (Perna spp) (Per v 1), avocado species (Persea spp) (Pers a 1, Pers a 1.0101, Pers a 4), parsley species (Petroselinum spp) (Pet c 1, Pet c 2, Pet c 3), canary grass species (Phalaris spp) (Pha a 1, Pha a 1.0101, Pha a 5, Pha a 5.0101, Pha a 5.02, Pha a 5.03, Pha a 5.04), bean species (Phaseolus spp) (Pha v 3, Pha v 3.0101, Pha v 3.0201, Pha v aAI, Pha v aAI.0101, Pha v chitinase, Pha v PHA, Pha v phytohemagglutinin), timothy species (Phleum spp) (Phl p 1, Phl p 1.0101, Phl p 1.0102, Phl p 11, Phl p 11.0101, Phl p 12, Phl p 12.0101, Phl p 12.0102, Phl p 12.0103, Phl p 13, Phl p 13.0101, Phl p 2, Phl p 2.0101, Phl p 3, Phl p 3.0101, Phl p 3.0102, Phl p 4, Phl p 4.0101, Phl p 4.0102, Phl p 4.0201, Phl p 4.0202, Phl p 4.0203, Phl p 4.0204, Phl p 5, Phl p 5.0101, Phl p 5.0102, Phl p 5.0103, Phl p 5.0104, Phl p 5.0105, Phl p 5.0106, Phl p 5.0107, Phl p 5.0108, Phl p 5.0109, Phl p 5.0201, Phl p 5.0202, Phl p 5.0203, Phl p 5.0204, Phl p 5.0205, Phl p 5.0206, Phl p 5.0207, Phl p 6, Phl p 6.0101, Phl p 6.0102, Phl p 7, Phl p 7.0101, Phl p P1-P2-P5-P6, Phl p P2-P6, Phl p P5-P1, Phl p P6-P2), Phoenix spp (Pho d 2, Pho d 2.0101, Pho d 40 kD, Pho d 90 kD), Phodopus spp (Pho s 21 kD), Phoma spp (Pho t 1), Phragmites spp (Phr a 1, Phr a 12, Phr a 13, Phr a 4, Phr a 5), ​​Phytolacca spp (Phy a RIP), Pimpinella spp (Pim a 1, Pim a 2),. Pinna spp. (Pin a 1), Piper spp. (Pip n 14 kD, Pip n 28 kD), Pisum spp. (Pis s 1, Pis s 1.0101, Pis s 1.0102, Pis s 2, Pis s 2.0101, Pis s 5, Pis s agglutinin, Pis s albumin), Pistacia spp. (Pis v 1, Pis v 1.0101, Pis v 2, Pis v 2.0101, Pis v 2.0201, Pis v 3, Pis v 3.0101, Pis v 4, Pis v 4.0101, Pis v 5, Pis v 5.0101), Platanus spp. (Pla a 1, Pla a 1.0101, Pla a 2, Pla a 2.0101, Pla a 3, Pla a 3.0101, Pla a 8), Platichthys spp. (Pla f 1), Plantago spp. (Pla 11, Pla 11.0101, Pla I 1.0102, Pla 11.0103, Pla I cytochrome C), Platanus spp. (Pla oc 1, Pla or 1, Pla or 1.0101, Pla or 2, Pla or 2.0101, Pla or 3, Pla or 3.0101, Pla or 4, Pla or CyP, Pla r 1), Plectropomus spp. (Ple ar 1), Pleospora spp. (Ple h 1), Plectropomus spp. (Ple le 1), Plodia spp. (Plo i 1, Plo i 1.0101, Plo i 2, Plo i 2.0101), Poa spp. (Poa p 1, Poa p 1.0101, Poa p 10, Poa p 12, Poa p 13, Poa p 2, Poa p 4, Poa p 5, Poa p 5.0101, Poa p 6, Poa p 7), Polistes spp (Pol a 1, Pol a 1.0101, Pol a 2, Pol a 2.0101, Pol a 5, Pol a 5.0101, Pol d 1, Pol d 1.0101, Pol d 1.0102, Pol d 1.0103, Pol d 1.0104, Pol d 4, Pol d 4.0101, Pol d 5, Pol d 5.0101, Pol e 1, Pol e 1.0101, Pol e 2, Pol e 4, Pol e 4.0101, Pol e 5, Pol e 5.0101, Pol f 5, Pol f 5.0101, Pol g 1, Pol g 1.0101, Pol g 2, Pol g 4, Pol g 5, Pol g 5.0101, Pol he MLT, Pol m 5, Pol m 5.0101), Polypedilum spp (Pol n 1), Pollicipes spp (Pol po 1), Pollachius spp (Pol vi 1), Polybia spp (Poly p 1, Poly p 1.0101, Poly p 2, Poly p 5, Poly s 5, Poly s 5.0101), Pomatomus spp (Porn sa 1), Pongo spp (Pon ab HSA), Pontastacus spp (Pon I 4, Pon I 4.0101, Pon I 7, Pon I 7.0101), Portunus spp (Por s 1, Por s 1.0101, Por s 1.0102, Por tr 1, Por tr 1.0101), Protortonia spp (Pro ca 38 kD), Procumbarus spp (Pro cl 1, Pro cl 1.0101, Pro cl 21 kD), Prosopis spp (Pro j 20 kD), Prunus spp (Pru ar 1, Pru ar 1.0101, Pru ar 3, Pru ar 3.0101, Pru av 1, Pru av 1.0101, Pru av 1.0201, Pru av 1.0202, Pru av 1.0203, Pru av 2, Pru av 2.0101, Pru av 3, Pru av 3.0101, Pru av 4, Pru av 4.0101, Pru c 1, Pru d 1, Pru d 2, Pru d 3, Pru d 3.0101, Pru d 4, Pru du 1, Pru du 2, Pru du 2S albumin, Pru du 3, Pru du 3.0101, Pru du 4, Pru du 4.0101, Pru du 4.0102, Pru du 5, Pru du 5.0101, Pru du 6, Pru du 6.0101, Pru du 6.0201, Pru du conglutinin, Pru p 1, Pru p 1.0101, Pru p 2, Pru p 2.0101, Pru p 2.0201, Pru p 2.0301, Pru p 3, Pru p 3.0101, Pru p 3.0102, Pru p 4, Pru p 4.0101, Pru p 4.0201, Pru sa 3), Psilocybe spp (Psi c 1, Psi c 1.0101, Psi c 2, Psi c 2.0101), Psoroptes spp (Pso o 1, Pso o 10, Pso o 10.0101, Pso o 11, Pso o 13, Pso o 14, Pso o 2, Pso o 21, Pso o 3, Pso o 5, Pso o 7), Puma spp (Pum c 1), Punica spp (Pun g 3), Pyrus spp (Pyr c 1, Pyr c 1.0101, Pyr c 3, Pyr c 3.0101, Pyr c 4, Pyr c 4.0101, Pyr c 5, Pyr c 5.0101, Pyr py 2), Quercus spp. (Que a 1, Que a 1.0101, Que a 1.0201, Que a 1.0301, Que a 1.0401, Que a 2, Que a 4), Rachycentron spp. (Rac ca 1), Rana spp. (Ran e 1, Ran e 1.0101, Ran e 2, Ran e 2.0101), Ranina spp. (Ran ra 1), Rangifer spp. (Ran t BLG), Rattus spp. (Rat n 1, Rat n 1.0101, Rat n casein, Rat n gelatin, Rat n IgG, Rat n phosvitin, Rat n RSA, Rat n transferrin), Rhizomucor spp. (Rhi m AP), Rhizopus spp. (Rhi nv lipase, Rhi o lipase), Rhomboplites spp. (Rho au 1), Rhodotorula spp. (Rho m 1, Rho m 1.0101, Rho m 2, Rho m 2.0101), Ricinus spp. (Ric c 1, Ric c 1.0101, Ric c 2, Ric c 3, Ric c 8, Ric c RIP), Rivulus spp. (Riv ma 1), Robinia spp. (Rob p 2, Rob p 4, Rob p glucanase), Rosa spp. (Ros r 3), Roystonea spp. (Roy e 2), Rubus spp. (Rub i 1, Rub i 1.0101, Rub i 3, Rub i 3.0101, Rub i chitinase, Rub i CyP), Saccharomyces spp. (Sac c carboxypeptidase Y, Sac c CyP, Sac c enolase, Sac c glucosidase, Sac c invertase, Sac c MnSOD, Sac c P2, Sac c profilin), Salvelinus spp. (Sal f 1), Salsola spp. (Sal k 1, Sal k 1.0101, Sal k 1.0201, Sal k 1.0301, Sal k 1.0302, Sal k 2, Sal k 2.0101, Sal k 3, Sal k 3.0101, Sal k 4, Sal k 4.0101, Sal k 4.0201, Sal k 5, Sal k 5.0101), Salvelinus spp. (Sal le vitellogenin), Salmo spp. (Sal s 1, Sal s 1.0101, Sal s 1.0201, Sal s 2, Sal s 2.0101, Sal s gelatin), Sambucus spp. (Sam n 1), Sander spp. (San lu 1), Saponaria spp. (Sap o RIP), Sardinops spp. (Sar m 1), Sarkidiornis spp. (Sar ml 1), Sardina spp. (Sar p 1), Sarcoptes spp. (Sar s 1, Sar s 14, Sar s 3, Sar s GST, Sar s PM), Sardinops spp. (Sar sa 1, Sar sa 1.0101), Schistosoma spp (Sch j GST, Sch j PM, Sch j Sj22, Sch j Sj67, Sch ma Sm20, Sch ma Sm21, Sch ma Sm22, Sch ma Sm31), Sciaenops spp (Sci oc 1), Scomber spp (Sco a 1), Scombermorus spp (Sco ca 1), Scomberomorus spp (Sco g 1), Scomber spp (Sco j 1, Sco ma 1, Sco s 1), Scolopendra spp (Sco y 7, Sco y 7.0101), Scylla spp (Scy o 1, Scy o 1.0101, Scy o 2, Scy pa 1, Scy pa 2, Scy s 1, Scy s 1.0101, Scy s 2), Sebastes spp (Seb fa 1, Seb in 1, Seb m 1, Seb m 1.0101, Seb m 1.0201), Secale spp (Sec c, Sec c 12, Sec c 13, Sec c 2, Sec c 20, Sec c 20.0101, Sec c 20.0201, Sec c 28, Sec c 3, Sec c 4, Sec c 4.0101, Sec c 4.0201, Sec c 5, Sec c 5.0101, Sec c akTI, Sec c akTI.0101), Senecio spp (Sen j MDH, Sen j PL), Sepia spp (Sep e 1, Sep e 1.0101), Sepioteuthis spp (Sep 11, Sep I 1.0101), Sepia spp. (Sep m 1), Seriola spp. (Ser d 1, Ser la 1), Sergestes spp. (Ser lu 1), Seriola spp. (Ser q 1, Ser ri 1), Sesamum spp. (Ses i 1, Ses i 1.0101, Ses i 2, Ses i 2.0101, Ses i 3, Ses i 3.0101, Ses i 4, Ses i 4.0101, Ses i 5, Ses i 5.0101, Ses i 6, Ses i 6.0101, Ses i 7, Ses i 7.0101, Ses i 8), Shigella spp. (Shi bo GST, Shi dy GST), Simulia spp. (Sim vi 1, Sim vi 2, Sim vi 3, Sim vi 4, Sim vi 70 kD), Sinapis spp. (Sin a 1, Sin a 1.0101, Sin a 1.0104, Sin a 1.0105, Sin a 1.0106, Sin a 1.0107, Sin a 1.0108, Sin a 2, Sin a 2.0101, Sin a 3, Sin a 3.0101, Sin a 4, Sin a 4.0101), Sinonovacula spp. (Sin c 1, Sin c Solenopsis spp (Sol g 2, Sol g 2.0101, Sol g 3, Sol g 3.0101, Sol g 4, Sol g 4.0101, Sol g 4.0201, Sol i 1, Sol i 1.0101, Sol i 2, Sol i 2.0101, Sol i 3, Sol i 3.0101, Sol i 4, Sol i 4.0101), Solenocera spp (Sol me 1), Solenopsis spp (Sol r 1, Sol r 2, Sol r 2.0101, Sol r 3, Sol r 3.0101, Sol s 2, Sol s 2.0101, Sol s 3, Sol s 3.0101, Sol s 4), Solea spp (Sol so 1, Sol so TPI), Solanum spp (Sola t 1, Sola t 1.0101, Sola t 2, Sola t 2.0101, Sola t 3, Sola t 3.0101, Sola t 3.0102, Sola t 4, Sola t 4.0101, Sola t 8, Sola t glucanase), Sorghum spp. Sor h 7), Sparus spp. (Spa a 1), Sphyrna spp. (Sph ti 1), Spirulina spp. (Spi mx beta_phycocyanin), Spinacia spp. (Spi o 2, Spi o RuBisCO), Squilla spp. (Squ ac 1, Squ ac 1.0101, Squ o 1, Squ o 1.0101), Staphylococcus spp. (Sta a FBP, Sta a SEA, Sta a SEB, Sta a SEC, Sta a SED, Sta a SEE, Sta a TSST), Stachybotrys spp. (Sta c 3, Sta c3.0101, Sta c cellulase, Sta c hemolysin, Sta c SchS34, Sta c stachyrase A), Stemphylium spp. (Ste b 1, Ste c 1, Ste v 1), Stolephorus spp. (Sto i 1), Struthio spp. (Str c 1, Str c 2, Str c 3), Streptococcus spp. (Str dy streptokinase), Streptomyces spp. (Str g pronase), Streptococcus spp. (Str pn PspC), Strongylocentrotus spp. (Str pu 18 kD, Str pu Vitellogenin), Streptococcus spp (Str py SPEA, Str py SPEC, Str py Streptokinase), Strongyloides spp (Str st 45 kD), Streptomyces spp (Str v PAT), Styela spp (Sty p 1), Suidasia spp (Sui m 1, Sui m 13, Sui m 2, Sui m 3, Sui m 5, Sui m 5.01, Sui m 5.02, Sui m 5.03, Sui m 6, Sui m 7, Sui m 8, Sui m 9), Sus spp. (Sus s ACTH, Sus s ALA, Sus s amylase, Sus s BLG, Sus s casein, Sus s casein-alpha S1, Sus s casein-alpha S2, Sus s casein-beta, Sus s casein-kappa, Sus s gelatin, Sus s HG, Sus s insulin, Sus s lipase, Sus s pepsin, Sus s phosvitin, Sus s PRVB, Sus s PSA, Sus s TCTP), Syntelopodeuma spp. (Syn y 7, Syn y 7.0101), Syringa spp. (Syr v 1, Syr v 1.0101, Syr v 1.0102, Syr v 1.0103, Syr v 2, Syr v 3, Syr v 3.0101), Tabanus spp. (Tab y 1, Tab y 1.0101, Tab y 2, Tab y 2.0101, Tab y 5, Tab y 5.0101), Tadorna spp. (Tad ra 1), Talaromyces spp. (Tal st 22, Tal st 3, Tal st 8), Taraxacum spp. (Tar o 18 kD), Taxodium spp (Tax d 2), Tegenaria spp (Teg d hemocyanin), Teladorsagia spp (Tel ci 3), Thaumetopoea spp (Tha p 1, Tha p 1.0101, Tha p 2, Tha p 2.0101), Theragra spp (The c 1), Thermomyces spp (The I lipase, The sp lipase, The sp xylanase), Thunnus spp (Thu a 1, Thu a 1.0101, Thu a collagen, Thu al 1, Thu at 1, Thu o. 1, Thu o collagen), Thuja spp. (Thu oc 3, Thu p 1), Thyrsites spp (Thyrsites spp) (Thy at 1) was identified as Thyrsites spp (Thy at 1). Todarodes spp (Tod p 1, Tod p 1.0101, Tod p 1.0102) Tox c 7.0101) (Toxocara spp) (Tox ca TES120, Tox ca TES26, Tox ca TES30) HSP70) in Trachypenaeus spp (Tra c 1) and Trachinotus spp (Tra ca 1). Triticum spp (Tri a 1, Tri a 10 kD, Tri a 12, Tri a 12.0101, Tri a 3, Tri 12.0104, Tri a 13, Tri a 14, Tri a 14,0101, Tri a 14.0201, Tri a 15, Tri a 15.0101, Tri a 18, Tri a 18.0101, Tri a 19, Tri a 2 Tri a 19.0101, Tri a 1, Tri a 1, Tri a 1, Tri a 23kd, Tri to 25, Tri to 25, Tri to 26, Tri to 26.0101, Tri to 27, Tri to 27.0101, Tri to 28, Tri to 28.0101, Tri to 29, Tri to 29,0101 to Tri 30.1.29. 30.0101, Tri to 31, Tri to 31.0101, Tri to 32, Tri to 32.0101, Tri to 33, Tri to 33.0101, Tri a 34, Tri a 34.0101, Tri a 35, Tri a 35.0101, Tri a 36, ​​Tri a 36.0101, Tri a 37, Tri a 37.0101, Tri a 4, Tri a 4.0101, Tri a 4.0201, Tri a 5, Tri a 7, Tri a aA_SI, Tri a alpha_gliadin, Tri a bA, Tri a Bd36K, Tri a beta_gliadin, Tri a chitinase, Tri a CM16, Tri a DH, Tri a endochitinase, Tri a gamma_gliadin, Tri a germin, Tri a gliadin, Tri a GST, Tri a LMW Glu, Tri a LMW-GS B16, Tri a LMW-GS P42, Tri a LMW-GS P73, Tri a LTP2, Tri a omega-2 gliadin, Tri a peroxidase, Tri a peroxidase 1, Tri a SPI, Tri a TLP, Tri a tritin, Tri a XI), Tritirachium spp (Tri al proteinase K), Tribolium spp (Tri ca 17, Tri ca 17.0101, Tri ca 7, Tri ca 7.0101), Trichostrongylus spp (Tri co 3, Tri co 3.0101), Trichophyton spp (Tri eq 4), Trigonella spp (Tri fg 1, Tri fg 2, Tri fg 3, Tri fg 4), Trichosanthes spp (Tri k RIP), Trichiurus spp (Tri le 1), Triticum spp (Tri m pelooki shidaze), Trichophyton spp (Tri me 2, Tri me 4), Trisetum spp (Tri p 1, Tri p 5), Trichinella spp (Tri 1 0101), Trichophyton spp (Tri me 2, Tri me 4), Trisetum spp (Tri p 1, Tri p 5), Trichinella spp (Tri 1 0101), Trichophyton spp (Tri me 2, Tri me 4), Trisetum spp (Tri p 1, Tri p 5), Trichinella spp (Tri 1 0101), Trichophyton spp (Tri me 2, Tri me 4), Trisetum spp (Tri p 1, Tri p 5), Trichinella spp (Tri 1 0101), Trichophyton spp (Tri me 2, Tri me 4), Trisetum spp (Tri p 1, Tri p 5), Trichinella spp (Tri 1 spp) (Tri ps 3, Tri ps 3.0101), Trichophyton spp (Tri r 2, Tri r 2.0101, Tri r 4, Tri r 4.0101), Trichoderma spp (Tri rs セルラーゼ), Triticum spp (Tri s 14), Trichophyton spp (Tri sc 2, Tri sc 4​​, Tri so 2), Trichinella spp (Tri sp 3, Tri sp 3.0101, Tri sp 3.0102, Tri sp 3.0103, Tri sp 3.0104, Tri sp 3.0105, Tri sp 3.0106), Trichophyton spp (Tri t 1, Tri t 1.0101, Tri t 4, Tri t 4.0101), Triticum spp (Tri td 14, Tri td akTI), Trichoderma spp (Tri v セルラーゼ), Trichophyton spp (Tri ye 4), Triatoma spp (Tria p 1, Tria p 1.0101), Triplochiton spp. (Trip s 1), Turbo spp. (Tur c 1, Tur c PM), Tyrophagus spp. (Tyr p 1, Tyr p 10, Tyr p 10.0101, Tyr p 10.0102, Tyr p 13, Tyr p 13.0101, Tyr p 2, Tyr p 2.0101, Tyr p 24, Tyr p 24.0101, Tyr p 3, Tyr p 3.0101, Tyr p 4, Tyr p 5, Tyr p 5.01, Tyr p 5.02, Tyr p 5.03, Tyr p 7, Tyr p alpha tubulin), Ulocladium spp. (Ulo a 1, Ulo at 1, Ulo b 1, Ulo c 1, Ulo co 1, Ulo cu 1, Ulo mu 1, Ulo ob 1, Ulo se 1, Ulo su 1, Ulo to 1), Uncia spp. (Unc u 1), Urophycis spp. (Uro to 1), Vaccinium spp. (Vac m 3), Varroa spp. (Var j 13 kD), Venerupis spp. (Ven ph 1, Ven ph 1.0101), Vespula spp. (Ves f 1, Ves f 2, Ves f 5, Ves f 5.0101, Ves g 1, Ves g 2, Ves g 5, Ves g 5.0101, Ves m 1, Ves m 1.0101, Ves m 2, Ves m 2.0101, Ves m 5, Ves m 5.0101, Ves m MLT, Ves p 1, Ves p 2, Ves p 5, Ves p 5.0101, Ves s 1, Ves s 1.0101, Ves s 2, Ves s 5, Ves s 5.0101, Ves v 1, Ves v 1.0101, Ves v 2, Ves v 2.0101, Ves v 2.(0201, Ves v 3, Ves v 3.0101, Ves v 5, Ves v 5.0101, Ves v 5-Pol a 5, Ves vi 5, Ves vi 5.0101), Vespa spp (Vesp c 1, Vesp c 1.0101, Vesp c 2, Vesp c 5, Vesp c 5.0101, Vesp c 5.0102, Vesp m 1, Vesp m 1.0101, Vesp m 5, Vesp m 5.0101, Vesp ma 1, Vesp ma 2, Vesp ma 5, Vesp ma MLT, Vesp v MLT), Vigna spp (Vig r 1, Vig r 1.0101, Vig r 17 kD, Vig r 5, Vig r 8S globulin, Vig r albumin, Vig r beta-conglycinin), Vitis spp (Vit v 1, Vit v 1.0101, Vit v 4, Vit v 5, Vit v glucanase, Vit v TLP), Xiphias spp (Xip g 1, Xip g 1.0101, Xip g 25 kD), Zea spp (Zea m 1, Zea m 1.0101, Zea m 11, Zea m 12, Zea m 12.0101, Zea m 12.0102, Zea m 12.0103, Zea m 12.0104, Zea m 12.0105, Zea m 13, Zea m 14, Zea m 14.0101, Zea m 14.0101), Zoarces spp. (Zoa a ISP III), and Zygophyllum spp. (Zyg f 2).

[0119] The compositions described herein may include multiple heterogenous antigens (e.g., multiple different APs). In some embodiments, the "heterogenous antigens" may be antigens of different origin, such as antigens derived from pathogens of different taxonomic groups, such as different strains, species, subgenera, genus, subfamilies, or families, and / or antigens derived from antigenically different pathogens (e.g., variants thereof). Those skilled in the art will appreciate that viruses are classified into various taxonomic groups. Each of the different APs of the multiple different APs may be different from each other.

[0120] At least two of the fusion proteins may differ from each other with respect to the AP, and the population of ENPs may thereby display a plurality of different APs. The population of ENPs may include one or more homotypic ENPs, and the fusion proteins of the homotypic ENPs may be identical to each other with respect to the AP, and the homotypic ENPs do not thereby display a plurality of different APs. The population of ENPs may include one or more heterotypic ENPs, and at least two of the fusion proteins of the heterotypic ENPs may differ from each other with respect to the AP, and the heterotypic ENPs thereby display a plurality of different APs. The population of ENPs may include a mixture of two or more homotypic ENPs that differ from each other with respect to the APs of the fusion proteins present in the two or more homotypic ENPs, and the population of ENPs thereby display a plurality of different APs. The population of ENPs may include a mixture of two or more heterotypic ENPs that differ from each other (two or more heterotypic ENPs that differ from each other with respect to the AP of the fusion protein for the two or more heterotypic ENPs), where the heterotypic ENPs are capable of eliciting a heterogeneous antibody response against a further infectious agent, and where the heterotypic ENPs do not display an AP derived from the further infectious agent.

[0121] In some embodiments, the plurality of different APs comprises between about 2 and about 500 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 128, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, antigenic polypeptides that are different from each other (e.g., 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, or a number or range between any two of these values); APs of the same protein type; and / or APs of different protein types.

[0122] The multiple APs can be of the same protein type, or corresponding proteins. APs of the same protein type may or may not have identical amino acid sequences, but generally share some sequence homology. For example, coronavirus S proteins from various coronaviruses are of the same protein type, or corresponding proteins. As another example, envelope proteins from various coronaviruses are considered to be of the same protein type, or corresponding proteins. In some embodiments, proteins from various coronavirus taxa that have the same function are considered to be of the same protein type, or corresponding proteins. In some embodiments, coronavirus antigens of the same protein type have at least 50% sequence identity, e.g., at least 65%, 70%, 80%, 90%, 95%, 98%, 99%, or more.

[0123] Alternatively, in some embodiments, the plurality of APs can include coronavirus proteins of various protein types. APs of different protein types typically have different functions. For example, the plurality of APs can include a coronavirus S protein or a portion thereof, as well as other coronavirus proteins (e.g., a coronavirus N protein or a portion thereof, a coronavirus HE protein or a portion thereof, a coronavirus papain-like protease or a portion thereof, a coronavirus 3CL protease or a portion thereof, and / or a coronavirus M protein or a portion thereof).

[0124] The same ENP may contain APs from two or more strains of the same family, genus, and / or species of infectious agent. Different APs may have sequence identity to one another of about, at least, or at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, or a number or range between any two of these values.

[0125] The plurality of different APs may include a plurality of coronavirus (CoV) antigens, and the plurality of CoV antigens may include a first CoV antigen of a first CoV and a second CoV antigen of a second CoV different from the first CoV. The plurality of CoV antigens may include a CoV spike protein (S protein) or a portion thereof, a CoV envelope protein (E protein) or a portion thereof, a CoV nucleocapsid protein (N protein) or a portion thereof, a CoV hemagglutinin-esterase protein (HE protein) or a portion thereof, a CoV papain-like protease or a portion thereof, a CoV 3CL protease or a portion thereof, a CoV membrane protein (M protein) or a portion thereof, or a combination thereof. The plurality of CoV antigens may include a CoV S protein or a portion thereof. The first CoV antigen, the second CoV antigen, or both may include a CoV S protein or a portion thereof. The AP may comprise an amino acid sequence that is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, or a number or range between any two of these values ​​identical to SEQ ID NO: 24.

[0126] The ratio of the number of first AP (e.g., first CoV antigen molecules) to the number of second AP (e.g., second CoV antigen molecules) ranges from 1:100 to 100:1 (e.g., 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.5, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:51, 1:52, 1:53, 1:54, 1:55, 1:56, 1:57, 1:58, 1:59, 1:60, 1:61, 1:62, 1:63, 1:64, 1:65, 1:66, 1:67, 1:68, 1:69, 1:70, 1:71, 1:72, 1:73, 1:74, 1:75, 1:76, 1:77, 1:78, 1:79, 1:80, 1:81, 1:82, 1:83, 1:84, 1:85, 1:86, 1:87, 1:88, 1:89, 1:90, 1:91, 1:92, 1:93, 1:94, 1:95, 1:96, 1:97, 1:98, 1:99, 1:100 to 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1, 83:1, 84:1, The ratio may be 85:1, 86:1, 87:1, 88:1, 89:1, 90:1, 91:1, 92:1, 93:1, 94:1, 95:1, 96:1, 97:1, 98:1, 99:1, 100:1, or any number or range between these values. The multiple CoV antigens may include three, four, five, six (size), seven, or eight CoV antigens, each of which is different from the others. The multiple CoV antigens may include at least a third CoV antigen of a third CoV and a fourth CoV antigen of a fourth CoV, and the first, second, third, and fourth CoVs may be different from each other.

[0127] The plurality of different (e.g., heterologous) APs can include at least m pathogenic antigens of an mth infectious agent, where m is an integer greater than 2 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 128, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, In some embodiments, m is an integer greater than 50 (e.g., 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, or a number or range between any two of these values), and wherein each mth pathogenic antigen is different (e.g., heterologous) from each other. In some embodiments, m is an integer greater than 50.The plurality of different APs include a first pathogenicity antigen (PA) of a first infectious agent (IA), a second PA of a second IA, a third PA of a third IA, a fourth PA of a fourth IA, a fifth PA of a fifth IA, a sixth PA of a sixth IA, a seventh PA of a seventh IA, an eighth PA of an eighth IA, a ninth PA of a ninth IA, a tenth PA of a tenth IA, an eleventh PA of an eleventh IA, and a twelfth PA of a twelfth IA. A, 13th IA, 13th PA, 14th IA, 14th PA, 15th IA, 15th PA, 16th IA, 16th PA, 17th IA, 17th PA, 18th IA, 18th PA, 19th IA, 19th PA, 20th IA, 20th PA, 21st IA, 22nd PA, 23rd IA, 24th PA, 25th 25th PA of IA, 26th PA of 26th IA, 27th PA of 27th IA, 28th PA of 28th IA, 29th PA of 29th IA, 30th PA of 30th IA, 31st PA of 31st IA, 32nd PA of 32nd IA, 33rd PA of 33rd IA, 34th PA of 34th IA, 35th PA of 35th IA, 36th PA of 36th IA, 37th PA of 37th IA The 46th PA of the 47th IA, the 48th PA of the 48th IA, the 39th PA of the 39th IA, the 40th PA of the 40th IA, the 41st PA of the 41st IA, the 42nd PA of the 42nd IA, the 43rd PA of the 43rd IA, the 44th PA of the 44th IA, the 45th PA of the 45th IA, the 46th PA of the 46th IA, the 47th PA of the 47th IA, the 48th PA of the 48th IA, the 49th PA of the 49th IA, and the 50th PA of the 50th IA. 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, 10th, 11th, 12th, 13th, 14th, 15th, 16th, 17th, 18th, 19th, 20th, 21st, 22nd, 23rd, 24th, 25th, 26th, 27th, 28th, 29th The 30th, 31st, 32nd, 33rd, 34th, 35th, 36th, 37th, 38th, 39th, 40th, 41st, 42nd, 43rd, 44th, 45th, 46th, 47th, 48th, 49th, and 50th pathogenic antigens may be the same as or different from each other.1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, 10th, 11th, 12th, 13th, 14th, 15th, 16th, 17th, 18th, 19th, 20th, 21st, 22nd, 23rd, 24th, 25th, 26th, 27th, 28th, 29th The 30th, 31st, 32nd, 33rd, 34th, 35th, 36th, 37th, 38th, 39th, 40th, 41st, 42nd, 43rd, 44th, 45th, 46th, 47th, 48th, 49th, and 50th infectious agents may be the same as or different from one another. The multiple different (e.g., heterogeneous) APs may include multiple CoV antigens, multiple influenza antigens, and / or multiple HIV antigens.

[0128] The compositions provided herein may induce a broad protective anti-infectious agent response by eliciting broadly neutralizing antibodies. For example, broadly neutralizing antibodies can neutralize coronaviruses from the same taxonomic group as the coronavirus antigen used to elicit the antibodies, as well as coronaviruses from a different taxonomic group. A broadly neutralizing response is sometimes referred to as a heteroneutralizing response. In some embodiments, the compositions described herein may elicit broadly neutralizing antibodies that neutralize one or more infectious agents from a subfamily, genus, subgenus, species, and / or strain that is different from the subfamily, genus, subgenus, species, and / or strain of the infectious agent from which the AP is derived to produce the fusion protein provided herein.

[0129] Enveloped Nanoparticles The ENP has at least about 2-fold (e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or a number or range between any of these values) increased activity compared to a multi-component nanoparticle approach, optionally compared to a SpyCatcher-based nanoparticle approach, or a lentiviral Gag-based approach. , or more of the AP, and / or may be at least as immunogenic (e.g., 1x, 1.5x, 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, 20x, 30x, 40x, 50x, 60x, 70x, 80x, 90x, 100x, or a number or range between any of these values), and further optionally, the multi-component nanoparticle approach comprises two or more distinct polypeptides.

[0130] The ENP may contain at least about 2-fold (e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or a number or range between any of these values) more of the AP compared to a nanoparticle approach that does not contain the ERD, and optionally compared to a SpyCatcher-based or Gag-based nanoparticle approach. , 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or any number or range between these values), and / or may be at least as immunogenic (e.g., 1-fold, 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or any number or range between these values).

[0131] The ENPs may have one or more dimensions of eukaryotic viruses. In some embodiments, less than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% of the ENPs in the population of ENPs have a particle size smaller than about 10 nm. In some embodiments, less than about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% of the ENPs in the population of ENPs have a particle size greater than about 80 nm. In some embodiments, the average diameter of the ENPs in the population of ENPs ranges from about 5 nm to about 80 nm, from about 15 nm to about 50 nm, or from about 20 nm to about 40 nm. The average diameter of the ENPs in the population of ENPs can be about 10 nm, about 12 nm, about 14 nm, about 16 nm, about 18 nm, about 20 nm, about 22 nm, about 24 nm, about 26 nm, about 28 nm, about 30 nm, about 32 nm, about 34 nm, about 36 nm, about 38 nm, about 40 nm, about 42 nm, about 44 nm, about 46 nm, about 48 nm, or about 50 nm; optionally, the average is the mean, median, or mode; optionally, the mean is the arithmetic mean, geometric mean, and / or harmonic mean.

[0132] In some embodiments, the ENPs have a minimum diameter of about 10 nm, about 12 nm, about 14 nm, about 16 nm, about 18 nm, about 20 nm, about 22 nm, about 24 nm, about 26 nm, about 28 nm, about 30 nm, about 32 nm, about 34 nm, about 36 nm, about 38 nm, about 40 nm, about 42 nm, about 44 nm, about 46 nm, about 48 nm, or about 50 nm. In some embodiments, the ENP is about 10 nm, about 12 nm, about 14 nm, about 16 nm, about 18 nm, about 20 nm, about 22 nm, about 24 nm, about 26 nm, about 28 nm, about 30 nm, about 32 nm, about 34 nm, about 36 nm, about 38 nm, about 40 nm, about 42 nm, about 44 nm, about 46 nm, about 48 nm, about 50 nm. nm, about 52 nm, about 54 nm, about 56 nm, about 58 nm, about 60 nm, about 62 nm, about 64 nm, about 66 nm, about 68 nm, about 70 nm, about 72 nm, about 74 nm, about 76 nm, about 78 nm, or about 80 nm.

[0133] In some embodiments, storage of the ENP at 4°C for at least 3 months reduces immunogenicity by less than about 1%, 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%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%. The composition may be stable for at least about 2 weeks, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, or about 1 year after storage as a liquid at a temperature of about 4°C. At least approximately 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, or a number or range between any two of these values, of the ENPs may be immunogenic for at least 1 month after storage as a liquid at a temperature of about 5°C.

[0134] Vectors and Carriers The nucleic acid compositions (e.g., n polynucleotides encoding n fusion proteins) are complexed or associated with one or more lipids or lipid-based carriers, thereby forming liposomes, lipid nanoparticles (LNPs), lipoplexes, and / or nanoliposomes, optionally encapsulating the nucleic acid compositions. In some embodiments, the nucleic acid compositions (e.g., n polynucleotides encoding n fusion proteins) are, comprise, or further comprise one or more vectors. At least one of the one or more vectors can be a viral vector, a plasmid, a transposable element, a naked DNA vector, a lipid nanoparticle (LNP), or any combination thereof. The viral vector may be an AAV vector, a lentiviral vector, a retroviral vector, an adenoviral vector, a herpes virus vector, a herpes simplex virus vector, a cytomegalovirus vector, a vaccinia virus vector, an MVA vector, a baculovirus vector, a vesicular stomatitis virus vector, a human papillomavirus vector, an avipox virus vector, a Sindbis virus vector, a VEE vector, a measles virus vector, an influenza virus vector, a hepatitis B virus vector, an integration-deficient lentivirus (IDLV) vector, or any combination thereof. The transposable element may be a piggybac transposon or a sleeping beauty transposon. The polynucleotide encoding the fusion protein may be contained in one or more vectors. The polynucleotides encoding the fusion proteins may be contained in the same vector and / or in different vectors. The polynucleotides encoding the fusion proteins may be present on the same nucleic acid and / or on different nucleic acids.

[0135] The one or more vectors may be DNA vaccines, including plasmid-based DNA vaccines, minicircle-based DNA vaccines, bacmid-based DNA vaccines, minigene-based DNA vaccines, ministring DNA (linear covalently closed DNA vector) vaccines, closed-ended linear duplex DNA (CELiD or ceDNA) vaccines, doggybone vaccines, and the like. TM The vaccine may be a DNA vaccine, a dumbbell-shaped DNA vaccine, or a minimalistic immunologically-defined gene expression (MIDGE)-vectored DNA vaccine. In some embodiments, the DNA vaccine elicits at least a 2-fold (e.g., 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 20-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, 100-fold, or any number or range between these values) greater neutralizing antibody response against an infectious agent compared to a DNA vaccine encoding the AP but not the ERD.

[0136] Polynucleotides encoding fusion proteins (e.g., n polynucleotides encoding n fusion proteins) may be operably linked to one or more promoters capable of directing transcription of the polynucleotides, which may include ubiquitous promoters, inducible promoters, tissue-specific promoters, and / or lineage-specific promoters. The ubiquitous promoters include cytomegalovirus (CMV) immediate early promoter, CMV promoter, simian virus 40 (SV40) (e.g., early or late), Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR) promoter, Rous sarcoma virus (RSV) long terminal repeat (LTR), RSV promoter, herpes simplex virus (HSV) (thymidine kinase) promoter, H5, P7.5, and P11 promoters from vaccinia virus, elongation factor 1-alpha (EF1a) promoter, early growth response 1 (EGR1), ferritin H (FerH), ferritin L (FerL), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), eukaryotic translation initiation factor 4A1 (EIF4A1), heat shock 70 kDa protein 5 (HSPA5), heat shock protein 90 (HSP1), and the like. kDa beta, member 1 (HSP90B1), heat shock protein 70 kDa (HSP70), beta-kinesin (β-KIN), human ROSA 26 locus, ubiquitin C promoter (UBC), phosphoglycerate kinase-1 (PGK) promoter, 3-phosphoglycerate kinase promoter, cytomegalovirus enhancer, human beta-actin (HBA) promoter, chicken beta-actin (CBA) promoter, CAG promoter, CASI promoter, CBH promoter, or any combination thereof.

[0137] As used herein, the term "promoter" refers to a nucleotide sequence that allows RNA polymerase to bind and direct transcription of a gene. Typically, promoters are located in the 5' non-coding region of a gene and are adjacent to the transcription start site of the gene. Sequence elements within a promoter that function to initiate transcription are often characterized by consensus nucleotide sequences. Examples of promoters include, but are not limited to, promoters derived from bacteria, yeast, plants, viruses, and mammals (e.g., humans). Promoters can be inducible, repressible, and / or constitutive. Inducible promoters initiate increased levels of transcription from DNA under their control in response to changes in culture conditions (e.g., temperature).

[0138] As used herein, the term "operably linked to" is used to describe the connection between a regulatory element and a gene or its coding region. Typically, gene expression is placed under the control of one or more regulatory elements (e.g., but not limited to, constitutive or inducible promoters, tissue-specific regulatory elements, and enhancers). A gene or coding region is said to be "operably linked to" or "operatively linked to" or "operably associated with" a regulatory element, meaning that the gene or coding region is controlled or influenced by the regulatory element. For example, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence.

[0139] The polynucleotide encoding the fusion protein may be operably linked to a tandem gene expression element (e.g., an internal ribosome entry site (IRES), foot-and-mouth disease virus 2A peptide (F2A), equine rhinitis A virus 2A peptide (E2A), porcine teschovirus 2A peptide (P2A), or Thosea asigna virus 2A peptide (T2A), or any combination thereof). The polynucleotide encoding the fusion protein may include a transcript stabilization element (e.g., a woodchuck hepatitis post-translational regulatory element (WPRE), a bovine growth hormone polyadenylation (bGH-polyA) signal sequence, a human growth hormone polyadenylation (hGH-polyA) signal sequence, or any combination thereof).

[0140] The nucleic acid composition may be or may include mRNA. The composition (e.g., nucleic acid composition) may be an mRNA vaccine. The mRNA may be formulated into lipid nanoparticles (LNPs). The term "lipid nanoparticle," also known as LNPs, refers to particles comprising one or more lipids and having at least one dimension on the order of nanometers (e.g., 1-1,000 nm). In some embodiments, such lipid nanoparticles comprise a cationic lipid and one or more excipients selected from neutral lipids, charged lipids, steroids, and polymer-conjugated lipids (e.g., PEGylated lipids). In some embodiments, the mRNA, or a portion thereof, is encapsulated in the lipid portion of the lipid nanoparticle or in an aqueous space enclosed by some or all of the lipid portion of the lipid nanoparticle, thereby protecting it from enzymatic degradation or other undesirable effects, such as adverse immune responses, induced by mechanisms of the host organism or cells. In some embodiments, the mRNA, or a portion thereof, is associated with the lipid nanoparticle. LNPs may include any lipid capable of forming particles to which one or more nucleic acid molecules are bound or in which one or more nucleic acid molecules are encapsulated. The term "lipid" refers to a group of organic compounds that are derivatives (e.g., esters) of fatty acids and are generally insoluble in water but soluble in many organic solvents. Lipids are generally divided into at least three classes: (1) "simple lipids," which include fats, oils, and waxes; (2) "compound lipids," which include phospholipids and glycolipids; and (3) "derived lipids," such as steroids.

[0141] LNPs may comprise one or more of ionizable cationic lipids, non-cationic lipids (e.g., neutral lipids), sterols, and PEG-modified lipids. LNPs may comprise 0.5-15 mol% PEG-modified lipids, 5-25 mol% non-cationic lipids, 25-55 mol% sterols, and 20-60 mol% ionizable cationic lipids. LNPs may comprise 40-55 mol% ionizable cationic lipids, 5-15 mol% neutral lipids, 35-45 mol% sterols, and 1-5 mol% PEG-modified lipids. In some embodiments, RNA (e.g., mRNA) of the present disclosure is formulated into lipid nanoparticles (LNPs). Lipid nanoparticles typically comprise ionizable cationic lipids, non-cationic lipids, sterols, and PEG-modified lipids along with a nucleic acid cargo of interest. Lipid nanoparticles of the present disclosure may be produced using components, compositions, and methods generally known in the art, e.g., PCT / US2016 / 052352; PCT / US2016 / 068300; PCT / US2017 / 037551; PCT / US2015 / 027400; PCT / US2016 / 047406; PCT / US2016 / 000129; PCT / US2016 / 014280; PCT / US2016 / 014280; PCT / US2017 / 038426; PCT / US2014 / 027077; PCT / US2014 / 055394; PCT / US2016 / 052117; PCT / US2012 / 069610; See PCT / US2017 / 027492; PCT / US2016 / 059575 and PCT / US2016 / 069491, all of which are incorporated by reference in their entireties into this application.

[0142] In some embodiments, the LNP comprises: 47 mol% ionizable cationic lipid, 11.5 mol% neutral lipid, 38.5 mol% sterol, and 3.0 mol% PEG-modified lipid; 48 mol% ionizable cationic lipid, 11 mol% neutral lipid, 38.5 mol% sterol, and 2.5 mol% PEG-modified lipid; 49 mol% ionizable cationic lipid, 10.5 mol% neutral lipid, 38.5 mol% sterol, and 2.0 mol% PEG-modified lipid; 50 mol% ionizable cationic lipid, 10 mol% neutral lipid, 38.5 mol% sterol, and 1.5 mol% PEG-modified lipid; or 51 mol% ionizable cationic lipid, 9.5 mol% neutral lipid, 38.5 mol% sterol, and 1.0 mol% PEG-modified lipid.

[0143] The ionizable cationic lipid may be heptadecan-9-yl 8((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate. The neutral lipid may be 1,2 distearoyl sn glycero-3 phosphocholine (DSPC). The sterol may be cholesterol. The PEG-modified lipid may be 1-monomethoxypolyethyleneglycol-2,3-dimyristylglycerol (PEG2000 DMG) with an average molecular weight of 2000 polyethylene glycol.

[0144] The lipid:mRNA wt / wt ratio may be from about 1:100 to about 100:1 (e.g., 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.5, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:51, 1:52, 1:53, 1:54, 1:55, 1:56, 1:57, 1:58, 1:59, 1:60, 1:61, 1:62, 1:63, 1:64, 1:65, 1:66, 1:67, 1:68, 1:69, 1:70, 1:71, 1:72, 1:73, 1:74, 1:75, 1:76, 1:77, 1:78, 1:79, 1:80, 1:81, 1:82, 1:83, 1:84, 1:85, 1:86, 1:87, 1:88, 1:89, 1:90, 1:91, 1:92, 1:93, 1:94, 1:95, 1:96, 1:97, 1:98, 1:99, 1:100 to 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.5:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 31:1, 32:1, 33:1, 34:1, 35:1, 36:1, 37:1, 38:1, 39:1, 40:1, 41:1, 42:1, 43:1, 44:1, 45:1, 46:1, 47:1, 48:1, 49:1, 50:1, 51:1, 52:1, 53:1, 54:1, 55:1, 56:1, 57:1, 58:1, 59:1, 60:1, 61:1, 62:1, 63:1, 64:1, 65:1, 66:1, 67:1, 68:1, 69:1, 70:1, 71:1, 72:1, 73:1, 74:1, 75:1, 76:1, 77:1, 78:1, 79:1, 80:1, 81:1, 82:1, 83:1, 84:1, The ratio may be 85:1, 86:1, 87:1, 88:1, 89:1, 90:1, 91:1, 92:1, 93:1, 94:1, 95:1, 96:1, 97:1, 98:1, 99:1, 100:1, or any number or range between any of these values.

[0145] LNPs may include cationic lipids. The cationic lipids may be cationizable, i.e., they become protonated as the pH decreases below the pKa of the lipid's ionizable group, but gradually become neutral at higher pH values. When positively charged, the lipids can associate with negatively charged nucleic acids. In some embodiments, the cationic lipids include zwitterionic lipids, which become positively charged as the pH decreases. LNPs may include any lipid capable of forming particles that bind to or encapsulate one or more nucleic acid molecules. In some embodiments, LNPs may include any additional cationic or cationizable lipid (i.e., any of a number of lipid species that have a net positive charge at a selected pH, such as physiological pH). Such lipids include, but are not limited to, N,N-dioleyl-N,N-dimethylammonium chloride (DODAC); N-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA); N,N-distearyl-N,N-dimethylammonium bromide (DDAB); N-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP); 3-(N-(N',N'dimethylaminoethane)-carbamoyl)cholesterol (DC-Chol), N-(1-(2,3-dioleoyloxy)propyl)N-2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate (DOSPA), dioctadecylamidoglycyl carboxyspermine (DOGS), and 1,2-dioleoyl-3-dimethylammonium propane. (DODAP), N,N-dimethyl-2,3-dioleoyloxy)propylamine (DODMA), and N-(1,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl ammonium bromide (DMRIE).

[0146] Additionally, many commercially available cationic lipids are available that may be used in the embodiments provided herein. These include, for example, LIPOFECTIN(登録商標) (Commercially available cationic liposomes containing DOTMA and 1,2-dioleoyl-sn-3 phosphoethanolamine (DOPE), GIBCO / BRL, Grand Island, NY); LIPOFECTAMINE (登録商標) Commercially available cationic liposomes containing N-(1-(2,3-dioleyloxy)propyl)-N-(2-(sperminecarboxamido)ethyl)-N,N-dimethylammonium trifluoroacetate (DOSPA) and DOPE (Gibco / BRL); and TRANSFECTAM (登録商標) (Commercially available cationic lipids include dioctadecylamidoglycyl carboxyspermine (DOGS) in ethanol, Promega Corp., Madison, Wis.) The following lipids are cationic and have a positive charge below physiological pH: DODAP, DODMA, DMDMA, 1,2-dilinoleyloxy-N,N-dimethylaminopropane (DLinDMA), and 1,2-dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA).

[0147] Exemplary neutral lipids include, for example, distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoyl-phosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), and dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl-phosphatidylethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidylethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, and 18-1-trans PE. Examples of neutral lipids include PE, 1-stearioyl-2-oleoylphosphatidyethanolamine (SOPE), and 1,2-dielideyl-sn-glycero-3-phosphoethanolamine (transDOPE). In some embodiments, the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC).

[0148] In some embodiments, the cationic lipid is an amino lipid. Useful suitable amino lipids include those described in WO2012 / 016184, which is incorporated herein by reference in its entirety. Representative amino lipids include, but are not limited to, 1,2-dilinoleyloxy-3-(dimethylamino)acetoxypropane (DLin-DAC), 1,2-dilinoleyloxy-3-morpholinopropane (DLin-MA), 1,2-dilinoleoyl-3-dimethylaminopropane (DLin-DAP), 1,2-dilinoleylthio-3-dimethylaminopropane (DLin-S-DMA), 1-linoleoyl-2-linoleyloxy-3-dimethylaminopropane (DLin-2-DMAP), and 1,2-dilinoleyloxy-3-trimethylaminopropane chloride salt. (DLin-TMA.Cl), 1,2-dilinoleoyl-3-trimethylaminopropane chloride salt (DLin-TAP.Cl), 1,2-dilinoleyloxy-3-(N-methylpiperazino)propane (DLin-MPZ), 3-(N,N-dilinoleylamino)-1,2-propanediol (DLinAP), 3-(N,N-dioleylamino)-1,2-propanediol (DOAP), 1,2-dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DMA), and 2,2-dilinoleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-K-DMA).

[0149] In some embodiments, the non-cationic lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3 ... 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-Diundecanoyl-sn-glycero-phosphocholine (DUPC), 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-Di-0-octadecenyl-sn-glycero-3-phosphocholine (18:0 diether PC), 1-oleoyl-2 Cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine (OChemsPC), 1-hexadecyl-sn-glycero-3-phosphocholine (C16 Lyso PC), 1,2-dilinolenoyl-sn-glycero-3-phosphocholine, 1,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1,2-didocohexaenoyl-sn-glycero-3-phosphocholine, 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2-dilinolenoyl-sn-glycero-3-phosphoethanolamine, 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine, 1,2-didocohexaenoyl-sn-glycero-3-phosphoethanolamine, 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), sphingomyelin, and mixtures thereof.

[0150] In some embodiments, the PEG-modified lipid comprises PEG-modified phosphatidylethanolamine, PEG-modified phosphatidic acid, PEG-modified ceramide, PEG-modified dialkylamine, PEG-modified diacylglycerol, PEG-modified dialkylglycerol, and mixtures thereof. In some embodiments, the PEG-modified lipid is DMG-PEG, PEG-c-DOMG (also referred to as PEG-DOMG), PEG-DSG, and / or PEG-DPG. In some embodiments, the sterol comprises cholesterol, fecosterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol, tomatidine, ursolic acid, alpha-tocopherol, and mixtures thereof.

[0151] In some embodiments, the nucleic acid composition comprising an mRNA sequence is a modified mRNA sequence. In this context, the modifications defined herein may result in stabilization of the mRNA sequence provided herein. In some embodiments, a stabilized mRNA sequence is thus provided, comprising at least one coding region (e.g., a polynucleotide encoding a fusion protein) as defined herein. In some embodiments, a nucleic acid composition comprising an mRNA sequence may thus be provided as a "stabilized mRNA sequence," i.e., an mRNA that is essentially resistant to in vivo degradation (e.g., by exo- or endo-nucleases). Such stabilization may be the result, for example, of a modified phosphate backbone of the mRNA provided herein. A backbone modification may be a chemical modification of the backbone phosphate of a nucleotide contained in the mRNA. Nucleotides that can be used in this context include, for example, phosphorothioate-modified phosphate backbones (e.g., in which at least one phosphate oxygen in the phosphate backbone is replaced by a sulfur atom). Stabilized mRNAs further include, for example, non-ionic phosphate analogs, such as alkyl phosphonates and aryl phosphonates, in which the charged phosphonate oxygen is replaced by an alkyl or aryl group, or phosphodiesters and alkyl phosphotriesters, in which the charged oxygen residue is present in an alkylated form. Such backbone modifications typically include, but are not limited to, modifications from the group consisting of methyl phosphonates, phosphoramidates, and phosphorothioates (e.g., cytidine-5'-O-(1-thiophosphate)). The term "mRNA modification" as used herein may refer to chemical modifications, including backbone modifications as well as sugar or base modifications. In this context, modified mRNAs (sequences) as defined herein may include nucleotide analogs / modifications, such as backbone, sugar, or base modifications.A backbone modification can be a modification in which the phosphate of the backbone of a nucleotide contained in an mRNA compound comprising an mRNA sequence defined herein is chemically altered. A sugar modification can be a chemical modification of the sugar of a nucleotide of an mRNA compound comprising an mRNA sequence defined herein. Furthermore, a base modification can be a chemical modification of the base substructure of a nucleotide of an mRNA compound comprising an mRNA sequence. In this context, the nucleotide analog or modification can be selected from nucleotide analogs applicable to transcription and / or translation.

[0152] The mRNAs provided herein may include a 5' untranslated region (UTR), a 3' UTR, and / or a cap (e.g., a CAP analog). The modified mRNA sequences defined herein may be modified by the addition of a so-called "5'-CAP structure," which may stabilize the mRNA as described herein. A 5'-CAP is generally an entity, typically a modified nucleotide, that "caps" the 5'-end of a mature mRNA. A 5'-CAP is typically formed by a modified nucleotide, particularly a guanine nucleotide derivative. In some embodiments, the 5'-CAP is attached to the 5'-end via a 5'-5'-triphosphate bond. The 5'-CAP may be methylated, e.g., m7GpppN, where N is the 5' nucleotide at the end of the nucleic acid bearing the 5'-CAP, typically at the 5'-end of the mRNA. m7GpppN is a 5'-CAP structure that naturally occurs in mRNA transcribed by polymerase II and, therefore, in some embodiments, is not considered a modification contained in a modified mRNA in this context. Thus, a modified mRNA sequence may contain m7GpppN as a 5'-CAP, but in addition, the modified mRNA sequence typically contains at least one additional modification as defined herein. A CAP analog refers to a non-polymerizable dinucleotide with CAP functionality that facilitates translation or localization and / or prevents degradation of an RNA molecule when incorporated at the 5'-end of the molecule. Non-polymerizable means that the CAP analog is incorporated only at the 5'-end, since it lacks a 5' triphosphate and therefore cannot be extended in the 3' direction by a template-dependent RNA polymerase.CAP analogs include, but are not limited to, chemical structures selected from the group consisting of m7GpppG, m7GpppA, m7GpppC; unmethylated CAP analogs (e.g., GpppG); dimethylated CAP analogs (e.g., m2,7GpppG), trimethylated CAP analogs (e.g., m2,2,7GpppG), dimethylated symmetric CAP analogs (e.g., m7Gpppm7G), or anti-reverse CAP analogs (e.g., ARCA; m7,2'OmeGpppG, m7,2'dGpppG, m7,3'OmeGpppG, m7,3'dGpppG, and their tetraphosphate derivatives) (Stepinski et al., 2001. RNA 7(10):1486-95). Additional CAP analogs have been previously described (U.S. Patent No. 7,074,596, WO2008 / 016473, WO2008 / 157688, WO2009 / 149253, WO2011 / 015347, and WO2013 / 059475).

[0153] The mRNA may contain one or more modified nucleotides selected from the group including pseudouridine, N-1-methyl-pseudouridine, 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, O(6)-methylguanine, and 2-thiocytidine. The mRNA may contain modified nucleotides in place of one or more uridines. The modified nucleoside may be selected from pseudouridine (ψ), N 1-methyl-pseudouridine (m1Ψ), and 5-methyl-uridine (m5U). In some embodiments, the non-naturally occurring modified nucleotides or nucleosides of the present disclosure are those that are commonly known or recognized in the art. Non-limiting examples of such non-naturally occurring modified nucleotides and nucleosides can be found, inter alia, in published U.S. application numbers PCT / US2012 / 058519; PCT / US2013 / 075177; PCT / US2014 / 058897; PCT / US2014 / 058891; PCT / US2014 / 070413; PCT / US2015 / 36773; PCT / US2015 / 36759; PCT / US2015 / 36771; or PCT / IB 2017 / 051367, all of which are incorporated by reference into this application.

[0154] Pharmaceutical Compositions and Therapeutic Uses Vaccine Composition The present application also provides vaccine compositions comprising the compositions described herein (e.g., nucleic acid compositions, populations of ENPs). Vaccine compositions may include compositions provided herein (e.g., nucleic acid compositions, populations of ENPs) in combination with one or more compatible and pharmaceutically acceptable carriers. For example, vaccine compositions may be or include mRNA vaccines, DNA vaccines, and / or populations of ENPs as described herein. Vaccine compositions are pharmaceutical compositions capable of eliciting a prophylactic (e.g., to prevent or delay the onset of a disease, or to prevent the onset of its clinical symptoms or the onset of subclinical symptoms) or therapeutic (e.g., to suppress or alleviate symptoms) immune response in a subject.

[0155] The phrase "pharmaceutically acceptable" is used herein to refer to agents, materials, compositions, and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0156] As used in this application, the phrase "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition, or vehicle (e.g., a liquid or solid filler, diluent, excipient, solvent, or encapsulating substance, etc., involved in carrying or transporting the target chemical from one organ or part of the body to another). Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the subject. Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; and (9) peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil. (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer; and (21) other non-toxic compatible substances used in pharmaceutical formulations.

[0157] In some embodiments, the pharmaceutically acceptable carrier comprises a pharmaceutically acceptable salt. As used herein, "pharmaceutically acceptable salt" includes a salt of the acid form of one of the components of the compositions described herein. These include organic or inorganic acid salts of amines. Preferred acid salts are hydrochlorides, acetates, salicylates, nitrates, and phosphates. Other suitable pharmaceutically acceptable salts are well known to those skilled in the art and include basic salts of various inorganic and organic acids.

[0158] The vaccine composition may further comprise a suitable adjuvant, which refers to any immunomodulatory substance that can be combined with the protein antigen described herein to enhance, improve, or otherwise modulate the immune response in a subject, such as immunostimulatory peptides, oligonucleotide CpG motifs, immunostimulatory carbohydrates and polysaccharides, immunostimulatory protein or peptide molecules (e.g., cytokines, chemokines, flagellin, and derivatives thereof), Freund's adjuvant, sapanin (e.g., matrix M1), lecithin, aluminum hydroxide, monophosphoryl lipid A, interleukin-12, STING agonists, Advax, and AS01. B, STING agonists (e.g., bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP or cdGMP)), and the like. In some embodiments, the nucleic acid composition comprises one or more polynucleotides encoding an immunostimulatory factor. In some embodime...

Claims

1. A composition comprising: a nucleic acid composition comprising a polynucleotide encoding a fusion protein; wherein the fusion protein comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD); and wherein multiple fusion proteins are capable of self-assembling into enveloped nanoparticles (ENPs) that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs.

2. A composition comprising: a nucleic acid composition comprising n polynucleotides each encoding an nth fusion protein; where n is an integer from 2 to 500. wherein each fusion protein comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD); wherein at least two of the fusion proteins are different with respect to the AP, and wherein multiple fusion proteins are capable of self-assembling into enveloped nanoparticles (ENPs) that are secreted from cells expressing the fusion proteins, thereby generating a population of ENPs.

3. 3. The composition of claim 1, wherein the fusion protein is capable of being displayed on the surface of a cell that expresses the fusion protein.

4. 3. The composition according to claim 1, wherein the self-assembly of ENPs is: No exogenous nucleic acid other than the nucleic acid composition is required. no exogenous components other than the fusion proteins are required; and / or Only a single component is required, optionally, said single component being said fusion protein.

5. 3. The composition of any one of claims 1 to 2, wherein the cells are: cells of interest; in vivo, ex vivo, or in situ cells; and / or Adherent or suspension cells.

6. 3. The composition of claim 1, wherein upon secretion from cells of a subject, the ENPs are capable of distribution in one or more tissues of a subject. Optionally, the one or more tissues comprise adrenal tissue, appendix tissue, bladder tissue, bone, intestinal tissue, brain tissue, breast tissue, bronchus, coronary tissue, ear tissue, esophageal tissue, eye tissue, gallbladder tissue, reproductive tissue, heart tissue, hypothalamus tissue, kidney tissue, large intestine tissue, intestinal tissue, laryngeal tissue, liver tissue, lung tissue, lymph node, oral tissue, nasal tissue, pancreatic tissue, parathyroid tissue, pituitary tissue, prostate tissue, rectal tissue, salivary gland tissue, skeletal muscle tissue, skin tissue, small intestine tissue, spinal cord, spleen tissue, stomach tissue, thymus tissue, tracheal tissue, thyroid tissue, ureteral tissue, urethral tissue, soft and connective tissue, peritoneal tissue, vascular tissue, adipose tissue, or any combination thereof. Further optionally, the ENP engages a plurality of immune cells in the one or more tissues, thereby mimicking a natural infection.

7. A composition comprising: a population of enveloped nanoparticles (ENPs), Here, each of the ENPs comprises multiple fusion proteins, each of which comprises an antigenic polypeptide (AP) and an endosomal sorting complex required for transport (ESCRT)-recruiting domain (ERD).

8. 10. The composition of any one of claims 1, 2 or 7, wherein the ENP comprises a lipid bilayer, optionally a lipid bilayer derived from the cell that secreted the ENP.

9. The composition of any one of claims 1, 2, or 7, wherein the ERD recruits one or more ESCRT proteins to the cytoplasmic tail of the fusion protein, and optionally, recruitment of ESCRT proteins via the ERD induces self-assembly and budding of ENPs.

10. The composition of any one of claims 1, 2 or 7, wherein the cytoplasmic portion of the fusion protein comprises the ERD, optionally, the cytoplasmic tail of the fusion protein comprises the ERD.

11. 10. The composition of any one of claims 1, 2 or 7, wherein the ERD interacts with the ESCRT proteins TSG101, NEDD4, and / or ALIX.

12. 10. The composition of any one of claims 1, 2 or 7, wherein the ERD comprises or is derived from: a non-human protein, optionally a non-mammalian protein, further optionally a chicken protein, a mouse protein, a lizard protein, a reptile protein, a hamster protein, or a goldfish protein; the ESCRT and ALIX binding region (EABR) of the human CEP55 protein, optionally residues 170 to 213; Syntenin-1, rat galectin-3 (rGalectin-3), Hrs, and / or CD2AP; a viral protein, optionally a fragment of a viral protein, further optionally a retrovirus protein, a herpes simplex virus protein, a vaccinia virus protein, a hepadnavirus protein, a togavirus protein, a flavivirus protein, an arenavirus protein, a coronavirus protein, an orthomyxovirus protein, a paramyxovirus protein, a bunyavirus protein, a bornavirus protein, a rhabdovirus protein, or a filovirus protein, optionally a Gag protein, further optionally a Gag protein from EIAV, HTLV-1, MLV, or MPMV, optionally a Gag protein from EIAV p9 and / or HIV-1 p6; and / or An Ebola protein, optionally EBOV VP40.

13. 10. The composition of any one of claims 1, 2, or 7, wherein the ERD comprises an amino acid sequence having at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 20 and 23.

14. 10. The composition of claim 1, 2, or 7, wherein the fusion protein comprises an endocytosis-preventing motif (EPM) capable of preventing endocytosis of the fusion protein.

15. The composition of any one of claims 1, 2 or 7, wherein the EPM comprises or is derived from a portion of the murine low-affinity gamma Fc region receptor II isoform FcRII-B1, optionally wherein the EPM comprises all or a portion of the cytoplasmic tail of FcRII-B1.

16. 10. The composition of any one of claims 1, 2 or 7, wherein the EPM comprises an amino acid sequence having at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO:

21.

17. 10. A composition according to any one of claims 1, 2 or 7, wherein the AP, or a part thereof, is displayed within the ENP and / or on the surface of the ENP.

18. 10. The composition of claim 1, 2 or 7, wherein the AP is: from about 1 amino acid to about 10,000 amino acids in length; comprising or derived from an antigenic protein associated with a disease or disorder, optionally an immunogenic variant and / or immunogenic fragment of said antigenic protein; comprising, or derived from, a conserved portion of the antigenic protein; present on and / or in the ENP in its native membrane-bound conformation; and / or Optionally, the AP comprises or is derived from a full-length surface protein of an infectious agent.

19. 10. The composition of claim 1, 2 or 7, wherein the disease or disorder is an infectious disease or disorder caused by an infectious agent, wherein the AP comprises or is derived from an antigenic protein of the infectious agent, and wherein the antigenic protein of the infectious agent is a pathogenic antigen.

20. A composition according to any one of claims 1, 2 or 7. wherein the disease or disorder is a disease associated with expression of a tumor-associated antigen, and wherein the antigenic protein is a tumor-associated antigen; wherein the disease or disorder is an autoimmune disease or disorder, and wherein the antigenic protein is an autoimmune antigen; and / or wherein the disease or disorder is an allergic disease or disorder, and wherein the antigenic protein is an allergic antigen.

21. 10. The composition of any one of claims 1, 2 or 7, wherein the AP comprises a membrane protein, optionally a multi-spanning transmembrane protein.

22. 10. The composition of claim 1, 2 or 7, wherein the AP is not configured to be a soluble protein, optionally the AP does not include one or more mutations configured to increase its solubility and / or stability.

23. 8. The composition of claim 1, 2 or 7, wherein the AP does not contain a transmembrane domain and / or is a soluble protein, and wherein the fusion protein comprises a transmembrane domain (TD).

24. 10. The composition of any one of claims 1, 2 or 7, wherein the transmembrane domain comprises or is derived from a non-human transmembrane protein, optionally a non-mammalian transmembrane protein.

25. 10. The composition of any one of claims 1, 2 or 7, wherein the TD comprises or is derived from a natural protein, a recombinant protein, and / or a synthetic protein, optionally a synthetic protein comprising predominantly hydrophobic residues.

26. 10. The composition of any one of claims 1, 2 or 7, wherein the fusion protein comprises one or more linkers, and wherein the one or more linkers are: one or more flexible amino acid residues, optionally from about 1 to about 18 flexible amino acid residues, further optionally, the flexible amino acid residues include glycine, serine, or a combination thereof; a glycine-serine (GS) linker, optionally 1 to 15 amino acids in length; and / or It is located between the ERD and AP, between the ERD and EPM, between the ERD and TD, between the EPM and TD, between the AP and EPM, and / or between the AP and TD.

27. 10. The composition of claim 1, 2, or 7, wherein at least two fusion proteins of the plurality of fusion proteins differ from each other with respect to the AP, and wherein the population of ENPs thereby displays a plurality of different APs.

28. A composition described in any one of claims 1, 2 or 7, wherein the heterotypic ENP is capable of inducing a heterologous antibody response against a further infectious agent, and wherein the heterotypic ENP does not display an AP derived from the further infectious agent.

29. 10. The composition of claim 1, 2 or 7, wherein the plurality of different APs comprises: Between about 2 and about 500 antigenic polypeptides that are different from each other; APs of the same protein type; and / or APs of different protein types.

30. The composition of any one of claims 1, 2 or 7, wherein the same ENP comprises APs from two or more strains of the same family, genus and / or species of infectious agent.

31. 10. The composition of any one of claims 1, 2 or 7, wherein the plurality of different APs have about, at least, or at least about, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% sequence identity to each other.

32. 10. The composition of any one of claims 1, 2, or 7, wherein the nucleic acid composition is complexed or associated with one or more lipids or lipid-based carriers, thereby forming liposomes, lipid nanoparticles (LNPs), lipoplexes, and / or nanoliposomes, optionally encapsulating the nucleic acid composition.

33. 10. The composition of any one of claims 1, 2 or 7, wherein the nucleic acid composition is, comprises, or further comprises one or more vectors. Optionally, at least one of the one or more vectors is a viral vector, a plasmid, a transposable element, a naked DNA vector, a lipid nanoparticle (LNP), or any combination thereof; Optionally, the viral vector is an AAV vector, a lentiviral vector, a retroviral vector, an adenoviral vector, a herpes virus vector, a herpes simplex virus vector, a cytomegalovirus vector, a vaccinia virus vector, an MVA vector, a baculovirus vector, a vesicular stomatitis virus vector, a human papillomavirus vector, an avipox virus vector, a Sindbis virus vector, a VEE vector, a measles virus vector, an influenza virus vector, a hepatitis B virus vector, an integration-deficient lentivirus (IDLV) vector, or any combination thereof; and Optionally, the transposable element is a piggybac transposon or a sleeping beauty transposon.

34. 10. The composition of any one of claims 1, 2 or 7, wherein the polynucleotide encoding the fusion protein is contained in one or more vectors. Optionally, the polynucleotides encoding the fusion proteins are contained in the same vector and / or in different vectors. Optionally, the polynucleotides encoding the fusion proteins are present on the same nucleic acid and / or on different nucleic acids.

35. 10. The composition of any one of claims 1, 2 or 7, wherein the one or more vectors is a DNA vaccine. Optionally, the polynucleotide encoding the fusion protein is operably linked to one or more promoters capable of directing transcription of said polynucleotide. Optionally, the DNA vaccine is a plasmid-based DNA vaccine, a minicircle-based DNA vaccine, a bacmid-based DNA vaccine, a minigene-based DNA vaccine, a ministring DNA (linear covalently closed DNA vector) vaccine, a closed-ended linear duplex DNA (CELiD or ceDNA) vaccine, a doggybone TM DNA vaccines, dumbbell-shaped DNA vaccines, or minimalistic immunologically-defined gene expression (MIDGE)-vectored DNA vaccines. Optionally, the DNA vaccine elicits at least a two-fold higher neutralizing antibody response against an infectious agent compared to a DNA vaccine encoding the AP but not the ERD.

36. A cell comprising the nucleic acid composition of any one of claims 1, 2 or 7.

37. A method of stimulating an immune response in a subject, wherein said subject is in need thereof, said method comprising: Administering to the subject a pharmaceutically effective amount of the composition of any one of claims 1, 2 or 7, thereby stimulating an immune response in the subject.

38. A method of treating or preventing a disease or disorder in a subject, wherein said subject is in need thereof, said method comprising: administering to the subject a pharmaceutically effective amount of the composition of any one of claims 1, 2 or 7, thereby treating or preventing the disease or disorder in the subject; Optionally, the disease or disorder is a disease or disorder caused by an infectious agent.

39. 38. The method of claim 37, wherein the object comprises: Human subjects; Is a newborn or infant aged 3 years or younger, 2 years or younger, 1.5 years or younger, 1 year or younger (12 months), 9 months, 6 months, or 3 months or younger, or is between 6 months and 2 years old; are immunocompromised, have lung disease, and / or are over 65 years old; have a chronic lung disease, optionally chronic obstructive pulmonary disease (COPD) or asthma; and / or The patient has an underlying co-morbidity, optionally wherein the underlying co-morbidity is selected from heart disease, diabetes, and lung disease.

40. 38. The method of claim 37, wherein the administering step comprises: Optionally, the composition is administered intramuscularly, further optionally in the deltoid region of the arm, including by aerosol delivery, nasal delivery, vaginal delivery, rectal delivery, buccal delivery, ocular delivery, local delivery, topical delivery, intracisternal delivery, intraperitoneal delivery, oral delivery, intramuscular injection, intravenous injection, subcutaneous injection, intranodal injection, intratumoral injection, intraperitoneal injection, intradermal injection, or any combination thereof.

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