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Epitope Enhancement of a CD4 HIV Epitope toward the Development of the Next Generation HIV Vaccine¹

Takahiro Okazaki^2,*, C. David Pendleton^*, Pablo Sarobe^3,*, Elaine K. Thomas^4,, Sujatha Iyengar, Clayton Harro, David Schwartz and Jay A. Berzofsky^5,*

^* Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Immunex, Seattle, WA 98101; and Johns Hopkins University Center for Immunization Research, Baltimore, MD 21205

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.