Peptide vaccine

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Peptide-based synthetic vaccines (epitope vaccines) are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. [1] Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response. [2]

Contents

History

The traditional vaccines are the whole live or fixed pathogens. The second generation of vaccines is mainly the protein purified from the pathogen. The third generation of vaccines is the DNA or plasmid that can express the proteins of the pathogen. Peptide vaccines are the latest step in the evolution of vaccines. [3]

Advantages and disadvantages

Compared with the traditional vaccines such as the whole fixed pathogens or protein molecules, the peptide vaccines have several advantages and disadvantages. [4]

Advantages:

Disadvantages:

Epitope design

The whole peptide vaccine is to mimic the epitope of an antigen, so epitope design is the most important stage of vaccine development and requires an accurate understanding of the amino acid sequence of the immunogenic protein interested. The designed epitope is expected to generate strong and long-period immuno-response against the pathogen. The followings are the points to consider when designing the epitope:

Applications

Chemical structures of peptide components of Alzheimer peptide vaccines (A) CAD106 and (B) ACI-35. Cr9b00472 0009.jpg
Chemical structures of peptide components of Alzheimer peptide vaccines (A) CAD106 and (B) ACI-35.

Cancer

Other common diseases

Related Research Articles

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<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

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<span class="mw-page-title-main">Conjugate vaccine</span> Type of vaccine

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Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

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Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, just a few crucial residues can activate a single antibody or TCR. This highlights the importance of structural homology in the theory of molecular mimicry. Upon activation, these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is one of several ways in which autoimmunity can be evoked. A molecular mimicking event is more than an epiphenomenon despite its low probability, and these events have serious implications in the onset of many human autoimmune disorders.

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Immunodominance is the immunological phenomenon in which immune responses are mounted against only a few of the antigenic peptides out of the many produced. That is, despite multiple allelic variations of MHC molecules and multiple peptides presented on antigen presenting cells, the immune response is skewed to only specific combinations of the two. Immunodominance is evident for both antibody-mediated immunity and cell-mediated immunity. Epitopes that are not targeted or targeted to a lower degree during an immune response are known as subdominant epitopes. The impact of immunodominance is immunodomination, where immunodominant epitopes will curtail immune responses against non-dominant epitopes. Antigen-presenting cells such as dendritic cells, can have up to six different types of MHC molecules for antigen presentation. There is a potential for generation of hundreds to thousands of different peptides from the proteins of pathogens. Yet, the effector cell population that is reactive against the pathogen is dominated by cells that recognize only a certain class of MHC bound to only certain pathogen-derived peptides presented by that MHC class. Antigens from a particular pathogen can be of variable immunogenicity, with the antigen that stimulates the strongest response being the immunodominant one. The different levels of immunogenicity amongst antigens forms what is known as dominance hierarchy.

Artificial antigen presenting cells (aAPCs) are engineered platforms for T-cell activation. aAPCs are used as a new technology and approach to cancer immunotherapy. Immunotherapy aims to utilize the body's own defense mechanism—the immune system—to recognize mutated cancer cells and to kill them the way the immune system would recognize and kill a virus or other micro-organisms causing infectious diseases. Antigen presenting cells are the sentinels of the immune system and patrol the body for pathogens. When they encounter foreign pathogens, the antigen presenting cells activate the T cells—"the soldiers of the immune system"— by delivering stimulatory signals that alert there is foreign material in the body with specific cell surface molecules (epitopes). aAPCs are synthetic versions of these sentinel cells and are made by attaching the specific T-cell stimulating signals to various macro and micro biocompatible surfaces like micron-sized beads. This can potentially reduce the cost while allowing control over generating large numbers of functional pathogen-specific T cells for therapy. Activated and stimulated T cells can be studied in this biomimetic contex and used for adoptive transfer as an immunotherapy.

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Neoepitopes are a class of major histocompatibility complex (MHC) bounded peptides. They represent the antigenic determinants of neoantigens. Neoepitopes are recognized by the immune system as targets for T cells and can elicit immune response to cancer.

<span class="mw-page-title-main">UB-612</span> Vaccine candidate against COVID-19

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References

  1. Skwarczynski M, Toth I (February 2016). "Peptide-based synthetic vaccines". Chemical Science. 7 (2): 842–854. doi:10.1039/C5SC03892H. PMC   5529997 . PMID   28791117.
  2. Melief CJ, van der Burg SH (May 2008). "Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines". Nature Reviews. Cancer. 8 (5): 351–360. doi:10.1038/nrc2373. PMID   18418403. S2CID   205468352.
  3. Schneble E, Clifton GT, Hale DF, Peoples GE (2016). "Peptide-Based Cancer Vaccine Strategies and Clinical Results". In Thomas S (ed.). Vaccine Design. Methods in Molecular Biology. Vol. 1403. New York, NY: Springer. pp. 797–817. doi:10.1007/978-1-4939-3387-7_46. ISBN   978-1-4939-3387-7. PMID   27076168.
  4. Skwarczynski M, Toth I (February 2016). "Peptide-based synthetic vaccines". Chemical Science. 7 (2): 842–854. doi:10.1039/C5SC03892H. PMC   5529997 . PMID   28791117.
  5. Pearson MS, Pickering DA, Tribolet L, Cooper L, Mulvenna J, Oliveira LM, et al. (May 2010). "Neutralizing antibodies to the hookworm hemoglobinase Na-APR-1: implications for a multivalent vaccine against hookworm infection and schistosomiasis". The Journal of Infectious Diseases. 201 (10): 1561–1569. doi: 10.1086/651953 . PMID   20367477.
  6. Diemert DJ, Pinto AG, Freire J, Jariwala A, Santiago H, Hamilton RG, et al. (July 2012). "Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths". The Journal of Allergy and Clinical Immunology. 130 (1): 169–76.e6. doi: 10.1016/j.jaci.2012.04.027 . PMID   22633322.
  7. Cooper JA, Hayman W, Reed C, Kagawa H, Good MF, Saul A (April 1997). "Mapping of conformational B cell epitopes within alpha-helical coiled coil proteins". Molecular Immunology. 34 (6): 433–440. doi:10.1016/S0161-5890(97)00056-4. PMID   9307059.
  8. Azmi F, Ahmad Fuaad AA, Skwarczynski M, Toth I (March 2014). "Recent progress in adjuvant discovery for peptide-based subunit vaccines". Human Vaccines & Immunotherapeutics. 10 (3): 778–796. doi:10.4161/hv.27332. PMC   4130256 . PMID   24300669.
  9. Malonis RJ, Lai JR, Vergnolle O (March 2020). "Peptide-Based Vaccines: Current Progress and Future Challenges". Chemical Reviews. 120 (6): 3210–3229. doi:10.1021/acs.chemrev.9b00472. PMC   7094793 . PMID   31804810.
  10. Marincola FM, Rivoltini L, Salgaller ML, Player M, Rosenberg SA (July 1996). "Differential anti-MART-1/MelanA CTL activity in peripheral blood of HLA-A2 melanoma patients in comparison to healthy donors: evidence of in vivo priming by tumor cells". Journal of Immunotherapy with Emphasis on Tumor Immunology. 19 (4): 266–277. doi:10.1097/00002371-199607000-00003. PMID   8877721.
  11. Neal DE, Sharples L, Smith K, Fennelly J, Hall RR, Harris AL (April 1990). "The epidermal growth factor receptor and the prognosis of bladder cancer". Cancer. 65 (7): 1619–1625. doi: 10.1002/1097-0142(19900401)65:7<1619::aid-cncr2820650728>3.0.co;2-q . PMID   2311071. S2CID   12449093.
  12. Palatnik-de-Sousa CB, Soares IS, Rosa DS (2018-04-18). "Editorial: Epitope Discovery and Synthetic Vaccine Design". Frontiers in Immunology. 9: 826. doi: 10.3389/fimmu.2018.00826 . PMC   5915546 . PMID   29720983.
  13. Firbas C, Jilma B, Tauber E, Buerger V, Jelovcan S, Lingnau K, et al. (May 2006). "Immunogenicity and safety of a novel therapeutic hepatitis C virus (HCV) peptide vaccine: a randomized, placebo controlled trial for dose optimization in 128 healthy subjects". Vaccine. 24 (20): 4343–4353. doi:10.1016/j.vaccine.2006.03.009. PMID   16581161.
  14. Atsmon J, Caraco Y, Ziv-Sefer S, Shaikevich D, Abramov E, Volokhov I, et al. (October 2014). "Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population". Vaccine. 32 (44): 5816–5823. doi:10.1016/j.vaccine.2014.08.031. PMID   25173483.
  15. van Doorn E, Liu H, Ben-Yedidia T, Hassin S, Visontai I, Norley S, et al. (March 2017). "Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine: Phase IIb study protocol". Medicine. 96 (11): e6339. doi:10.1097/md.0000000000006339. PMC   5369918 . PMID   28296763.
  16. Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, et al. (June 2011). "The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects". The Journal of Neuroscience. 31 (25): 9323–9331. doi:10.1523/jneurosci.0293-11.2011. PMC   6623465 . PMID   21697382.
  17. Wang CY, Finstad CL, Walfield AM, Sia C, Sokoll KK, Chang TY, et al. (April 2007). "Site-specific UBITh amyloid-beta vaccine for immunotherapy of Alzheimer's disease". Vaccine. 25 (16): 3041–3052. doi:10.1016/j.vaccine.2007.01.031. PMID   17287052.
  18. Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Poghosyan A, et al. (March 2013). "Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial". The Journal of Neuroscience. 33 (11): 4923–4934. doi:10.1523/jneurosci.4672-12.2013. PMC   3634356 . PMID   23486963.
  19. Lacosta AM, Pascual-Lucas M, Pesini P, Casabona D, Pérez-Grijalba V, Marcos-Campos I, et al. (January 2018). "Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase I trial". Alzheimer's Research & Therapy. 10 (1): 12. doi: 10.1186/s13195-018-0340-8 . PMC   5789644 . PMID   29378651.
  20. Hickman DT, López-Deber MP, Ndao DM, Silva AB, Nand D, Pihlgren M, et al. (April 2011). "Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases". The Journal of Biological Chemistry. 286 (16): 13966–13976. doi: 10.1074/jbc.m110.186338 . PMC   3077597 . PMID   21343310.
  21. Kontsekova E, Zilka N, Kovacech B, Novak P, Novak M (2014). "First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model". Alzheimer's Research & Therapy. 6 (4): 44. doi: 10.1186/alzrt278 . PMC   4255368 . PMID   25478017.