title: Correlates of protection efficacy induced by vaccinia virus-specific CD8+ T-cell epitopes in the murine intranasal challenge model.
abstract: The recent identification of a large array of different vaccinia virus-derived CD8(+) T-cell epitopes offers a unique opportunity to systematically analyze the correlation between protective efficacy and variables such as kinetics of expression and function of viral proteins, binding affinity to MHC molecules, immunogenicity, and viral antigen processing/presentation. In the current study, 49 different H-2(b) restricted epitopes were tested for their ability to protect peptide-immunized C57Bl/6 mice from lethal i.n. challenge with vaccinia virus. The epitopes varied greatly in their ability to confer protection, ranging from complete protection with minimal disease to no protection at all. The function or kinetics of the viral antigen expression did not correlate with protective efficacy. However, binding affinity partially predicted protection efficacy and ultimately epitope immunogenicity and recognition of infected cells offered the best correlation.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Moutaftsi
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Howard
authors.initials: H
authors.lastname: Grey
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D014615:Vaccinia / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte