Pathogenic Epitopes, Heterologous Immunity and Vaccine Design

Overview

Journal Nat Rev Microbiol

Specialties Infectious Diseases
Microbiology

Date 2007 Jun 15

PMID 17558423

Citations 58

Authors

Raymond M Welsh

Robert S Fujinami

Affiliations

Soon will be listed here.

Abstract

Substantial research has been directed towards the development of a new generation of vaccines that are based on the inclusion of immunogenic epitopes in recombinant vectors. Here we examine the evidence that under certain conditions immunogenic epitopes can do more harm than good and might therefore be considered pathogenic. We suggest that the specific removal of such pathogenic epitopes from vaccines might increase their prophylactic potential, while minimizing the risk of side-effects from vaccine use.

Citing Articles

Deep learning enhances the prediction of HLA class I-presented CD8 T cell epitopes in foreign pathogens.

Wohlwend J, Nathan A, Shalon N, Crain C, Tano-Menka R, Goldberg B Nat Mach Intell. 2025; 7(2):232-243.

PMID: 40008296 PMC: 11847706. DOI: 10.1038/s42256-024-00971-y.

Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability.

Mai K, Pan W, Lin Z, Wang Y, Yang Z Adv Biotechnol (Singap). 2025; 3(1):5.

PMID: 39883362 DOI: 10.1007/s44307-025-00057-9.

Developing a universal multi-epitope protein vaccine candidate for enhanced borna virus pandemic preparedness.

Zhang J, Yang Y, Wang B, Qiu W, Zhang H, Qiu Y Front Immunol. 2024; 15:1427677.

PMID: 39703502 PMC: 11655343. DOI: 10.3389/fimmu.2024.1427677.

Computational design and evaluation of a polyvalent vaccine for viral nervous necrosis (VNN) in fish to combat Betanodavirus infection.

Moin A, Rani N, Sharker Y, Ahammed T, Rahman U, Yasmin S Sci Rep. 2024; 14(1):27020.

PMID: 39505874 PMC: 11542017. DOI: 10.1038/s41598-024-72116-5.

Rational design and computational evaluation of a multi-epitope vaccine for monkeypox virus: Insights into binding stability and immunological memory.

Kaur A, Kumar A, Kumari G, Muduli R, Das M, Kundu R Heliyon. 2024; 10(16):e36154.

PMID: 39247273 PMC: 11380015. DOI: 10.1016/j.heliyon.2024.e36154.

References

Wilson D, Wilson D, Schroder K, Pinilla C, Blondelle S, Houghten R . Specificity and degeneracy of T cells. Mol Immunol. 2004; 40(14-15):1047-55. DOI: 10.1016/j.molimm.2003.11.022. View

Zarozinski C, Fynan E, Selin L, Robinson H, Welsh R . Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein. J Immunol. 1995; 154(8):4010-7. View

Wang L, Fujinami R . Enhancement of EAE and induction of autoantibodies to T-cell epitopes in mice infected with a recombinant vaccinia virus encoding myelin proteolipid protein. J Neuroimmunol. 1997; 75(1-2):75-83. DOI: 10.1016/s0165-5728(96)00235-4. View

Cornberg M, Chen A, Wilkinson L, Brehm M, Kim S, Calcagno C . Narrowed TCR repertoire and viral escape as a consequence of heterologous immunity. J Clin Invest. 2006; 116(5):1443-56. PMC: 1435724. DOI: 10.1172/JCI27804. View

WEINSTEIN L, Meade R . Respiratory manifestations of chicken pox; special consideration of the features of primary varicella pneumonia. AMA Arch Intern Med. 1956; 98(1):91-9. DOI: 10.1001/archinte.1956.00250250097013. View

Welsh R, Selin L, Szomolanyi-Tsuda E . Immunological memory to viral infections. Annu Rev Immunol. 2004; 22:711-43. DOI: 10.1146/annurev.immunol.22.012703.104527. View

Lawson T, Man S, Williams S, Boon A, Zambon M, Borysiewicz L . Influenza A antigen exposure selects dominant Vbeta17+ TCR in human CD8+ cytotoxic T cell responses. Int Immunol. 2001; 13(11):1373-81. DOI: 10.1093/intimm/13.11.1373. View

Li J, Melenhorst J, Hensel N, Rezvani K, Sconocchia G, Kilical Y . T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus. J Gen Virol. 2006; 87(Pt 10):2951-2960. DOI: 10.1099/vir.0.82094-0. View

Tuohy V, Thomas D, Haqqi T, Yu M, Johnson J . Determinant-regulated onset of experimental autoimmune encephalomyelitis: distinct epitopes of myelin proteolipid protein mediate either acute or delayed disease in SJL/J mice. Autoimmunity. 1995; 21(3):203-14. DOI: 10.3109/08916939509008017. View

10.

Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D . Diversity considerations in HIV-1 vaccine selection. Science. 2002; 296(5577):2354-60. DOI: 10.1126/science.1070441. View

11.

Varga S, Wang X, Welsh R, Braciale T . Immunopathology in RSV infection is mediated by a discrete oligoclonal subset of antigen-specific CD4(+) T cells. Immunity. 2001; 15(4):637-46. DOI: 10.1016/s1074-7613(01)00209-6. View

12.

Clute S, Watkin L, Cornberg M, Naumov Y, Sullivan J, Luzuriaga K . Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. J Clin Invest. 2005; 115(12):3602-12. PMC: 1288832. DOI: 10.1172/JCI25078. View

13.

Zhou S, Ou R, Huang L, Moskophidis D . Critical role for perforin-, Fas/FasL-, and TNFR1-mediated cytotoxic pathways in down-regulation of antigen-specific T cells during persistent viral infection. J Virol. 2001; 76(2):829-40. PMC: 136836. DOI: 10.1128/jvi.76.2.829-840.2002. View

14.

Tsunoda I, Kuang L, Kobayashi-Warren M, Fujinami R . Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection. J Virol. 2005; 79(23):14640-6. PMC: 1287580. DOI: 10.1128/JVI.79.23.14640-14646.2005. View

15.

Anderson R, Bennink J, Yewdell J, Maloy W, Coligan J . Influenza basic polymerase 2 peptides are recognized by influenza nucleoprotein-specific cytotoxic T lymphocytes. Mol Immunol. 1992; 29(9):1089-96. DOI: 10.1016/0161-5890(92)90041-u. View

16.

Boniface J, Reich Z, Lyons D, Davis M . Thermodynamics of T cell receptor binding to peptide-MHC: evidence for a general mechanism of molecular scanning. Proc Natl Acad Sci U S A. 1999; 96(20):11446-51. PMC: 18053. DOI: 10.1073/pnas.96.20.11446. View

17.

Wedemeyer H, Mizukoshi E, Davis A, Bennink J, Rehermann B . Cross-reactivity between hepatitis C virus and Influenza A virus determinant-specific cytotoxic T cells. J Virol. 2001; 75(23):11392-400. PMC: 114725. DOI: 10.1128/JVI.75.23.11392-11400.2001. View

18.

Sospedra M, Zhao Y, Zur Hausen H, Muraro P, Hamashin C, de Villiers E . Recognition of conserved amino acid motifs of common viruses and its role in autoimmunity. PLoS Pathog. 2005; 1(4):e41. PMC: 1315278. DOI: 10.1371/journal.ppat.0010041. View

19.

Tsunoda I, Libbey J, Kobayashi-Warren M, Fujinami R . IFN-gamma production and astrocyte recognition by autoreactive T cells induced by Theiler's virus infection: role of viral strains and capsid proteins. J Neuroimmunol. 2005; 172(1-2):85-93. DOI: 10.1016/j.jneuroim.2005.11.004. View

20.

Zhao Z, Granucci F, Yeh L, Schaffer P, CANTOR H . Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science. 1998; 279(5355):1344-7. DOI: 10.1126/science.279.5355.1344. View