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Correlates of protection efficacy induced by VACV‐specific CD8+ T cell epitopes in the murine intranasal challenge model
Author(s) -
Moutaftsi Magdalini,
SalekArdakani Shahram,
Croft Michael,
Grey Howard,
Sette Alessandro
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.859.7
Subject(s) - epitope , vaccinia , immunization , virology , nasal administration , immunology , t cell , cd8 , antigen , peptide vaccine , immunity , biology , medicine , immune system , recombinant dna , biochemistry , gene
Vaccinia virus (VACV) was used to eradicate smallpox and is considered the gold standard of vaccines. Elucidating the immunobiology of protection will reveal vaccinology principles that can be applied to future vaccine development. The identification of 49 VACV‐specific CD8+ T cell epitopes offers a unique opportunity to systematically analyze the correlation between protective efficacy and the characteristics of T cell responses. All epitopes were tested for their ability to protect peptide‐immunized C57Bl/6 mice from lethal intranasal challenge with VACV‐WR. The epitopes varied significantly in their capacity to confer protection; 15 were 75–00% protective, 22 were 25–5% protective and 12 were less than 25% protective. Measurement of IFN‐ γ following peptide immunization demonstrated that induction of high IFN‐γ correlated with high protection efficacy, whereas low IFN‐γt confer any protection. However, for some epitopes the IFN‐γtion did not correlate with protective efficacy. Ongoing studies aim to identify the underlying mechanisms that induce protective immunity by characterizing the T cell responses elicited by epitope immunization and infection. These issues are relevant for the development of new vaccine constructs, in which inclusion of isolated antigens associated with detrimental responses could jeopardize vaccine efficacy. Grant Support: NO1‐AI40024