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Epitope enhancement of a CD4 HIV epitope toward the development of the next generation HIV vaccine
(American Association of Immunologists, 2006) Schwartz, D. (David); Pendleton, C.D. (C. David); Harro, C. (Clayton); Berzofsky, J.A. (Jay A.); Okazaki, T. (Takahiro); Thomas, E.K. (Elaine K.); Iyengar, S. (Sujatha); Sarobe, P. (Pablo)
Virus-specific CD4+ T cell help and CD8+ cytotoxic T cell responses are critical for maintenance of effective immunity in chronic viral infections. The importance of CD4+ T cells has been documented in HIV infection. To investigate whether a stronger CD4+ T cell response can be induced by modifications to enhance the T1 epitope, the first CD4+ T cell epitope discovered in HIV-1-gp120, we developed a T1-specific CD4+ T cell line from a healthy volunteer immunized with a canarypox vector expressing gp120 and boosted with recombinant gp120. This T1-specific CD4+ T cell line was restricted to DR13, which is common in U.S. Caucasians and African-Americans and very frequent in Africans. Peptides with certain amino acid substitutions in key positions induced enhanced specific CD4+ T cell proliferative responses at lower peptide concentration than the original epitope. This relatively conserved CD4 epitope improved by the epitope enhancement strategy could be a component of a more effective second generation vaccine construct for HIV infection.