94 results about "Multi epitope" patented technology

Provided is a method for using a multi-epitope antigen to construct an RNA vaccine for feline infectious peritonitis virus (FIPV). The method relates to an isolated nucleic acid molecule. The nucleic acid molecule comprises: at least one of a first nucleic acid fragment, a second nucleic acid fragment, a third nucleic acid fragment, a fourth nucleic acid fragment and a fifth nucleic acid fragment, wherein the first nucleic acid fragment is derived from the N-terminal domain (NTD) of the N protein of the FIPV strain QS, the second nucleic acid fragment is derived from the C-terminal domain (CTD) of the N protein from the FIPV strain QS, the third nucleic acid fragment encodes the NSP12 protein of the FIPV strain QS, the fourth nucleic acid fragment is derived from the epitope HR2_4 of the S protein of the FIPV strain 79-1146, the fifth nucleic acid fragment is derived from the epitope HR2_11 of the S protein of the FIPV strain 79-1146, and the nucleic acid molecule is RNA.

The invention discloses a preparation method and application of porcine pseudorabies virus multi-epitope polypeptide, and belongs to the technical field of veterinary biological products. The multi-epitope polypeptide comprises a cytotoxic T cell epitope, a helper T cell epitope and a linear B cell epitope; the cell epitopes are screened from key immunogenic proteins of the pseudorabies virus by using an immunoinformatics method. The porcine pseudorabies virus multi-epitope polypeptide designed by the invention is high in safety, has better antigenicity and physicochemical properties, can be efficiently expressed, and can be recognized by a pseudorabies virus specific antibody. By applying the porcine pseudorabies virus multi-epitope polypeptide, high-level specific antibodies and cellular immune response can be continuously induced to generate, strong protective efficacy is generated, and mice can be protected from death when infected with a lethal dose of porcine pseudorabies virus. Therefore, the multi-epitope polypeptide disclosed by the invention can be used as an alternative antigen of a porcine pseudorabies virus vaccine, the use of active virus is avoided, and a tool is provided for eradication of porcine pseudorabies virus.

The invention discloses a porcine rotavirus VP7 protein conservative dominant B cell antigen epitope peptide or a combination thereof or a nucleic acid molecule and application thereof, and further discloses a porcine rotavirus VP7 protein multi-epitope fusion protein and a preparation method and application thereof. The multi-epitope fusion protein disclosed by the invention not only can induce high-level specific antibody response and cellular immune response aiming at the VP7 protein and effectively inhibit porcine rotavirus infection, but also has relatively high safety and stability. Compared with the traditional fusion protein, the multi-epitope fusion protein disclosed by the invention has remarkable advantages in the aspects of production cost, immune efficacy and the like, and a feasible porcine rotavirus prevention and control scheme is provided for the pig industry.

In various embodiments immunogenic nanoparticles are provided that are capable of raising an immune response directed against SARS-CoV-2. In certain embodiments the immunogenic nanoparticles comprise mRNA multi-epitope vaccines that can be used in combination with or independent of other covid-19 vaccines (e.g., the spike protein mRNA vaccine(s)) to invoke a strong CD8+ or CD4+ T-cell as well as neutralizing antibody producing B-cell responses. In certain embodiments this vaccine is based on the rational combination of well-conserved T- and B-cell epitopes identified COVID-19 and viral variants.

The invention relates to the technical field of bovine viral diarrhea virus detection, in particular to a bovine viral diarrhea virus multi-epitope fusion protein and application thereof, a coding gene of the bovine viral diarrhea virus multi-epitope fusion protein is a nucleotide sequence as shown in SEQ ID NO.5 and corresponds to an amino acid sequence as shown in SEQ ID NO.9, and the coding gene of the bovine viral diarrhea virus multi-epitope fusion protein is an amino acid sequence as shown in SEQ ID NO.9. The recombinant plasmid comprises a coding gene of the bovine viral diarrhea virus multi-epitope fusion protein. The bovine viral diarrhea virus monoclonal antibody is used as a coating antibody, and the bovine viral diarrhea virus multi-epitope fusion protein is used as a marker antigen, so that early infection cases can be found, and a detection result can be provided for health management of cattle herds in time, so that corresponding prevention and control or treatment measures can be taken in time, and the detection efficiency is improved. Different subtypes of BVDVs can be detected more widely, and the applicability to detection of different popular subtypes of BVDVs in different regions is improved.

The invention provides an avian adenovirus D11 type tandem multi-epitope vaccine, and belongs to the technical field of veterinary vaccines. According to the invention, an amino acid sequence of fiber protein of the fowl adenovirus D11 type is analyzed, 10 potential B cell epitopes are screened out, 10 antigen epitopes are artificially synthesized to prepare the vaccine, and six antigen epitopes with high neutralizing antibody titer are screened out by immunizing chicken. Flexible peptides are designed among the screened six antigen epitopes for connection, and a series multi-epitope antigen is designed. The oil emulsion vaccine is prepared by expressing tandem multi-epitope antigen protein through recombinant escherichia coli, purifying through a nickel column, and emulsifying with a mineral oil adjuvant. All test chickens immunized by the series multi-epitope vaccine in an over-dose manner have no abnormities in spirit, ingestion and water drinking, injection parts have no red and swollen reactions, and the vaccine is good in safety. The series multi-epitope vaccine has a good immune effect, can enable the immunized chicken to generate a neutralizing antibody to achieve challenge protection, and can block the detoxification of the challenge chicken.

The invention discloses a multi-epitope peptide of novel coronavirus, a vaccine as well as a preparation method and application of the multi-epitope peptide, and belongs to the technical field of preparation of polypeptide vaccines. The multi-epitope peptide of the novel coronavirus not only contains T cell epitopes, but also contains B cell epitopes, and can induce humoral immunity and cellular immunity responses of an organism at the same time; the vaccine comprises epitopes from four antigenic proteins of novel coronavirus, and can induce comprehensive immune response. According to the multi-epitope peptide vaccine based on the novel coronavirus, the nano-carrier KFE8 serves as a delivery carrier, different antigen epitopes of the same pathogen or antigen epitopes of different pathogens can be presented in a mixed mode, safety is good, large-scale rapid preparation is achieved in an emergency state, and the vaccine is suitable for large-scale popularization and application. The coronavirus vaccine is a novel coronavirus universal vaccine which can cover various pathogen subtypes and induce broad-spectrum and long-term immune effects.

In order to seek an echinococcosis antigen which has good immunogenicity and can activate an organism to generate an effective immune response against echinococcosis granulosa infection, the invention provides an echinococcosis multi-epitope antigen and application thereof in preparation of a vaccine for preventing echinococcosis. The multi-epitope antigen is formed by sequentially connecting CTLA-4-lgV, a T cell epitope of EgA31, a T cell epitope of EgG1Y162, a B cell epitope of EgA31 and a B cell epitope of EgG1Y162 in series, the multi-epitope antigen can be specifically combined with serum of a cystic echinococcosis patient, a mouse immunized by a vaccine can generate specific B cell response and generate specific cellular immunity and an antibody, and the multi-epitope antigen has good immunogenicity.

The invention is applicable to the technical field of genetic engineering and biological medicine, and provides construction of a fusion recombinant protein ABT for preventing brucellosis and application of the fusion recombinant protein ABT in preparation of protective vaccines. The fusion recombinant protein ABT is composed of an immunological enhancement antigen and a multi-epitope tandem antigen, wherein the immunological enhancement antigen (named as A) comprises a Brucella ribosome L7 / L12 protein and a PADRE sequence; the multi-epitope tandem antigen is formed by connecting a dominant B cell epitope part (named as B), a dominant Tc cell epitope part and a dominant Th cell epitope part (named as T) in series, wherein the dominant B cell epitope part (named as B) is derived from Brucella SurA, OMP31, BP26 and Trigger factor proteins. The ABT Brucella multi-epitope subunit vaccine prepared by mixing the fusion recombinant protein ABT and an immunologic adjuvant has the characteristics of good purity, high safety and strong immunogenicity, can stimulate an organism to generate a protective antibody, and has long antibody maintenance time.

A chimeric nucleotide sequence that corresponds to an encoded fusion protein comprising a polyepitope resulting from selecting and juxtaposing multiple epitopes from a coronavirus protein to induce an immune response in mammals. In one embodiment, said fusion protein comprises: a) a first peptide consisting of epitopes found in the amino acid sequence of replicase polyprotein 1ab (PR1ab); b) a first spacer; c) a modified form of herpes simplex virus type 1 (HSV-1) glycoprotein D (gD). In one embodiment, the replicase polyprotein is defined by SEQ ID NO: 96 flanked by a gD fragment comprising the amino acid sequence defined by SEQ ID NO: 98 in the N-terminal portion and another gD fragment comprising the amino acid sequence defined by SEQ ID NO: 100 in the C-terminal region. Use of the fusion protein has surprising results in inducing cellular and humoral immune responses against coronavirus, SARS-COV-2, and related viruses.

A polyclonal antibody composition specifically binds the pTonB epitope (SEQ ID NO: 11) from Acinetobacter baumannii and is elicited by immunization with a multi-epitope antigen comprising thioredoxin leader, rigid linker, and kernels including SEQ ID NOs: 6, 7, 11, 12, and 8. These antibodies enhance opsonophagocytic killing of A. baumannii Ci79 via classical complement activation and Fey receptor-mediated phagocytosis by bone marrow-derived macrophages. Absorption of pTonB-specific antibodies reduces killing by >70%, confirming epitope dominance. Passive transfer of the composition protects >60% of mice in a lethal intranasal challenge model. Pharmaceutical compositions, treatment methods (alone or with antibiotics like colistin), prophylactic uses, diagnostic kits, and polyclonal compositions are disclosed for combating multidrug-resistant A. baumannii infections.

The invention discloses a preparation method and application of a hexavalent multi-epitope fusion protein of avian pathogenic Escherichia coli. The invention preferably selects antigenic epitopes of the curli fimbriae subunit CsgA, lipoprotein SlyB, maltose porin LamB, outer membrane protein PhoE, proteolytic enzyme activator NlpD and lipoprotein Pal main structural subunit of avian pathogenic Escherichia coli, and preferably connects with the heat-labile enterotoxin LTb fusion protein in series to construct an antigenic multi-epitope fusion protein of six proteins of avian pathogenic Escherichia coli. The antigenic multi-epitope fusion protein has a wide serotype coverage, is non-allergenic, has strong immunogenicity, and produces strong specific humoral immunity and cellular immune response after immunizing animals.

The application discloses a porcine rotavirus VP7 protein conserved dominant B cell antigen epitope peptide or a combination thereof or a nucleic acid molecule and application, and further discloses a porcine rotavirus VP7 protein polyepitope fusion protein and a preparation method and application thereof.The polyepitope fusion protein can not only induce high-level specific antibody response and cellular immune response to the VP7 protein, effectively inhibit porcine rotavirus infection, but also has high safety and stability.Compared with a traditional fusion protein, the polyepitope fusion protein has significant advantages in production cost and immunization efficacy, and provides a feasible porcine rotavirus prevention and control scheme for the pig industry.

The invention discloses a multi-epitope fusion protein based on porcine rotavirus VP7 and VP8 double targets as well as a preparation method and application of the multi-epitope fusion protein. According to the invention, salmonella typhimurium flagellin FliCS.T is taken as a skeleton, dominant neutralizing epitopes of VP7 and VP8 are accurately integrated, and the multi-epitope fusion antigen FliCS.T-VP7 + VP8 is constructed. The fusion protein has two immunological advantages: an FliCS.T skeleton has TLR5 adjuvant activity, so that innate immunity and adaptive immunity of a host can be efficiently activated; key neutralizing epitopes of porcine rotaviruses VP7 and VP8 are synchronously presented through a multi-epitope strategy, and high-titer specific neutralizing antibody and potent cellular immune response aiming at two structural proteins can be induced in vivo. The invention provides the multi-epitope fusion antigen of the porcine rotavirus, which integrates high immunogenicity and broad-spectrum neutralization protection, and a feasible technical scheme is provided for prevention and control of the porcine rotavirus.

The invention discloses a preparation method and application of a vibrio outer membrane protein A multi-epitope antigen and a recombinant antigen thereof, and is characterized in that a protein multi-epitope antigen sequence synthesized by outer membrane proteins of vibrio splendidus, vibrio parahaemolyticus and vibrio alginolyticus is designed by utilizing a multi-epitope technology, and the amino acid sequence of the protein multi-epitope antigen sequence is shown as SEQ ID NO.4; the preparation method of the multi-epitope recombinant antigen comprises the following steps: synthesizing a multi-epitope gene according to a multi-epitope antigen amino acid sequence, connecting the multi-epitope gene to a pET-28a (+) vector, transforming a plasmid containing the multi-epitope gene into a protein expression type competent cell, screening out positive clones, and performing protein expression; the method comprises the following steps: carrying out protein purification by using affinity chromatography to obtain a multi-epitope recombinant antigen, further preparing a multi-epitope antibody by using the multi-epitope recombinant antigen, and detecting whether a to-be-detected sample solution contains vibrio or not by using the multi-epitope antibody as a labeled protein and using a trace thermophoresis technology, so that the method has the advantages of high detection speed and strong specificity.

The invention discloses a porcine rotavirus VP8 protein dominant B cell neutralizing epitope peptide, a multi-epitope fusion protein and application of the multi-epitope fusion protein. The FliCS.T-VP8 multi-epitope fusion protein prepared by the invention is a multi-epitope fusion protein which takes salmonella typhimurium flagellin FliCS.T as a molecular skeleton and integrates the dominant B cell neutralizing epitope of the VP8 protein of the porcine rotavirus. According to the design, immunodominance epitope screening, multi-epitope fusion protein construction and genetic engineering technologies are fused, and the immunogenicity and immune protection efficacy of the fusion protein are remarkably enhanced. The FliCS.T-VP8 multi-epitope fusion protein not only can effectively induce high-level VP8 protein specific antibody response and cellular immune response, but also shows good porcine rotavirus neutralizing activity. In addition, the fusion protein has relatively high safety and stability, and has the potential of being used as an efficient subunit vaccine for preventing and controlling porcine rotavirus infection in the pig industry.

The present invention relates to a multi-epitope antigen comprising 20 epitope masses of from 20 to 36 amino acids, from a protein selected from the group consisting of NanA, PcsB, PhtD, Ply, PncO, StkP, PspA-F1 and PspA-F2. In addition, the invention relates to an immunogenic composition comprising said antigen and a pharmaceutically acceptable vehicle and / or adjuvant. In addition, the invention also discloses a pneumococcus diagnostic kit, which comprises the antigen combined with a detectable fraction or a bioactive fragment thereof; an antibody generated from the antigen; and instructions for use. Furthermore, the invention relates to the use of said antigens for the preparation of vaccines for the prevention of diseases caused by pneumococcal bacteria and for the production of monoclonal and polyclonal antibodies. Finally, the present invention relates to an in vitro diagnostic method of pneumococci comprising contacting said antigen bound to a detectable fraction or a biologically active fragment thereof with a sample of bodily fluids selected from mucus and urine expelled from blood, lower respiratory tract.

This invention relates to the application of the avian adenovirus serotype 4 multi-epitope recombinant chimeric protein rcF2 in the preparation of a kit for detecting avian adenovirus serotype 4 antibodies. The amino acid sequence of the avian adenovirus serotype 4 multi-epitope recombinant chimeric protein rcF2 is shown in SEQ ID NO.1. This invention utilizes the multi-epitope recombinant chimeric protein rcF2 to establish an indirect ELISA detection method and kit for detecting avian adenovirus serotype 4. This recombinant chimeric protein can be recognized by avian adenovirus serotype 4 positive sera, and the detection sensitivity of positive sera samples can reach 1:16000. It shows no cross-reactivity with antibodies against other pathogens, indicating that the ELISA detection method based on this multi-epitope recombinant chimeric protein rcF2 is simple to operate, enhances detection sensitivity, and has good specificity and repeatability.

The present invention provides a tandem multi-epitope vaccine against fowl adenovirus type D11, belonging to the technical field of veterinary vaccines. The present invention analyzes the amino acid sequence of the fiber protein of fowl adenovirus type D11, screens out 10 potential B-cell epitopes, artificially synthesizes 10 antigenic epitopes to prepare a vaccine and immunizes chickens to screen out 6 antigenic epitopes with relatively high neutralizing antibody titers. Flexible peptides are designed to be linked between the 6 screened antigenic epitopes to design a tandem multi-epitope antigen. The tandem multi-epitope antigen protein is expressed by recombinant Escherichia coli, emulsified with a mineral oil adjuvant after purification by a nickel column to prepare an oil emulsion vaccine. All the experimental chickens immunized with the tandem multi-epitope vaccine at an overdose showed no abnormalities in spirit, feeding and drinking, and there was no swelling reaction at the injection site, indicating good vaccine safety. The tandem multi-epitope vaccine has a good immunization effect, can enable the immunized chickens to produce neutralizing antibodies, achieve protection against challenge, and can block the excretion of challenged chickens.

The application discloses a SARS-CoV-2 epitope type vaccine multi-epitope combination and application, and belongs to the technical field of coronavirus vaccine research and development.The first aspect of the application relates to a fusion protein, which comprises in sequence: (a) a SARS-CoV-2 spike protein receptor binding domain or a functional fragment thereof; (b) a T cell epitope domain, comprising: a CTL epitope cluster, the CTL epitope cluster comprising at least one CD8+ T cell epitope polypeptide selected from SEQ ID NO: 1-15; and (c) an immunoglobulin Fc domain.The application adopts a tandem strategy of immunodominant epitopes + conserved epitopes, predicts high-affinity T cell epitopes by computational biology methods, evaluates the HLA restriction in different populations, introduces a flexible linker peptide for optimization design, evaluates the immune effect difference of different combinations through in vitro and animal models, analyzes the synergistic or competitive relationship between epitopes, and optimizes the vaccine design.Through systematic comparison of the immunological effect difference of different epitope combinations and the adaptability to various vaccine platforms, the application establishes an optimized safe, efficient, broad-spectrum and long-acting multi-epitope vaccine design strategy, and has significant application value and important transformation value.

The invention belongs to the technical field of genetic engineering, and particularly relates to a bovine group A rotavirus multi-epitope fusion protein and application thereof. The invention provides a bovine group A rotavirus multi-epitope peptide based on a ferritin nano-carrier, a fusion protein and application of the bovine group A rotavirus multi-epitope peptide and the fusion protein. The multi-epitope peptide disclosed by the invention is a multi-epitope fusion antigen which is formed by splicing cytotoxic T lymphocyte epitopes, helper T cell epitopes and B cell epitopes with high conservative property and strong immunogenicity and is formed by screening and obtaining the cytotoxic T lymphocyte epitopes, helper T cell epitopes and B cell epitopes with high conservative property and strong immunogenicity on the basis of VP4 and VP7 protein sequences of bovine group A rotaviruses by utilizing an immunoinformatics technology. Immunological evaluation shows that the monoclonal antibody has good antigen specificity and neutralizing activity. Animal experiment results show that the epitope peptide and the fusion protein can induce an organism to generate high-level neutralizing antibodies aiming at BRVA G6, G8, G10 and other multi-genotype strains, and the broad spectrum and durability of immune protection are remarkably improved.

Fusion proteins that include a backbone protein and at least one heterologous epitope from enterotoxigenic E. coli are provided. In some aspects, the fusion proteins are multiepitope fusion antigen proteins that include an LT B domain. In some aspects, the LT B domain is directly fused to an LT A domain (for example, the LT B domain does not include a starting methionine or signal sequence). In other aspects, the LT B domain includes a starting methionine and signal sequence. Methods of inducing an immune response in pigs utilizing the fusion proteins, such as an immune response that is protective against porcine post-weaning diarrhea, are also provided.

The present application relates to the technical field of vaccine preparation, and discloses a recombinant herpes zoster vaccine composition based on a multi-epitope chimeric antigen and a nano adjuvant, which comprises the following components in parts by weight: 1-3 parts of a multi-epitope chimeric antigen; 2-5 parts of a nano adjuvant; 0.5-1.5 parts of chitosan or trehalose; and 0.1-0.5 parts of other auxiliary materials, wherein the multi-epitope chimeric antigen comprises multiple immune epitopes of varicella zoster virus and is used for activating T cell and B cell immune responses, and the nano adjuvant comprises: 1-3 parts of a metal organic framework material and 1-3 parts of a carbon nanotube; the metal organic framework is an MIL-88B structure based on iron ions; and the carbon nanotube is functionally modified through acid pickling and ultraviolet light irradiation. The present application realizes the synergistic effect of antigen conformation maintenance, uniform compounding and stable reconstitution by constructing a nano composite structure and introducing a stabilizer and a microwave freeze-drying process.

The application discloses a bovine parainfluenza virus 3A and 3C type polyepitope antigen peptide, a complex thereof and application. The polyepitope antigen peptides BPMEV-3A and BPMEV-3C have amino acid sequences as shown in SEQ ID NO:1 and SEQ ID NO:3 respectively, and are connected by screening CTL epitopes, HTL epitopes and B cell epitopes from HN and F proteins of BPIV-3A and BPIV-3C strains. Animal immunization tests show that the antigen peptide and the complex thereof can effectively stimulate the body to produce specific IgG antibodies and neutralizing antibodies, induce Th1 type cellular immune response, and effectively eliminate viruses and reduce lung tissue lesions, and show good immunogenicity and protection effect. The application provides an efficient and safe vaccine candidate for prevention and control of BPIV-3, and has a good application prospect.

The invention discloses a recombinant bacillus calmette-guerin vaccine for expressing O and A type multi-epitope fusion peptides of foot and mouth disease viruses and application of the recombinant bacillus calmette-guerin vaccine, and belongs to the field of biotechnology and veterinary vaccines. The amino acid sequence of the multi-epitope fusion peptide is shown as SEQ ID NO: 1, the multi-epitope fusion peptide comprises dominant immune T cell and B cell antigen epitopes from a plurality of O-type and A-type foot-and-mouth disease virus epidemic strains, and a mycobacterium signal peptide is fused at the N terminal. The recombinant strain rBCG-MIPGA is successfully constructed by carrying out codon optimization on the fusion gene, cloning the fusion gene to a pMV306 vector and carrying out electrotransfection on BCG. The recombinant BCG can simultaneously excite high-titer specific antibodies aiming at foot-and-mouth disease virus type O and type A and remarkable T cell immune response, shows lasting and broad-spectrum protection potential, and has great application value in the aspect of preparing safe, efficient and broad-spectrum foot-and-mouth disease vaccines.

The invention discloses a Mycobacterium tuberculosis epitope mRNA (messenger Ribonucleic Acid) vaccine simulated, predicted and screened by a computer, which is prepared by the following steps: bacterial protein sequence acquisition and signal peptide analysis: acquiring amino acid sequences of proteins ESAT6, CFP10, Ag85A, Ag85B, TB10.4, PPE68, PPE18 and Rv1813c through a database; the method comprises the following steps: analyzing physicochemical properties of proteins, including the number of amino acids, the molecular weight, the instability index and the overall average value of water solubility, analyzing and predicting the allergy of the epitopes by using a server, and generating all potential mutants by using the server to predict and measure the toxicity of the epitopes; the multi-epitope mRNA vaccine candidate is successfully constructed by adopting computer simulation screening and optimization of the mycobacterium tuberculosis multi-epitope antigen, the vaccine design scheme is efficient, controllable and broad-spectrum, a theoretical basis and a candidate construct are provided for early research and development of tuberculosis vaccines, and the vaccine is expected to be used for prevention and control of tuberculosis and has positive influence on public health.

The application relates to the technical field of detecting O-type foot-and-mouth disease virus antibodies, and specifically discloses a multi-epitope VP1 fusion protein of O-type foot-and-mouth disease virus, a virus-like particle, a polyclonal antibody and application of the multi-epitope VP1 fusion protein, the virus-like particle, the polyclonal antibody and the like. The application takes the virus-like particle as a competitive antigen, takes the polyclonal antibody as a labeled antibody, and establishes a method for detecting O-type foot-and-mouth disease virus antibodies based on a competition method. The method not only has the advantages of simple operation, short detection time and the like, but also covers main topological types of O-type foot-and-mouth disease virus, avoids missing detection, and has the advantages of high specificity, high sensitivity, good stability and the like.

According to the invention, dominant antigen epitopes of main outer membrane proteins OspA, OspB and OspC of borrelia burgdorferi are screened out, and a multi-epitope fusion vaccine containing the epitopes and application are constructed. The vaccine design not only improves the specificity and immunogenicity of the antigen. Compared with a traditional antigen epitope screening and construction strategy, the method has the advantages that the cycle is shortened, the cost is reduced, meanwhile, the limitations of many and complex antigens, large toxic and side effects and the like of a traditional vaccine are overcome, the operation process is simplified, the method is more suitable for large-scale epitope screening, popularization and application, and a new thought and strategy are provided for research and development of borrelia burgdorferi vaccines.

The present disclosure provides compositions and methods related to multiparatopic aptamers. In particular, the present disclosure provides nucleic acid aptamers capable of binding multiple distinct epitopes on a target biomolecule, as well as corresponding methods of generating and characterizing the multiparatopic aptamers.

The present disclosure provides a therapy with vaccine compositions including multiepitopic polypeptides, recombinant nucleic acids encoding multiepitopic polypeptides and methods of use thereof. Also provided herein are T-cell receptors (TCRs) that can recognize one or more epitopes of the multiepitopic polypeptides. The therapy provided herein can comprise (i) a TCR, a recombinant nucleic acid encoding the TCR, or cells comprising the TCR or the recombinant nucleic acid encoding the TCR, and (ii) a vaccine composition described herein. The methods and compositions provided herein can be used for the treatment of cancer.