Epitope enhancement of a CD4 HIV epitope toward the development of the next generation HIV vaccine

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 elective second generation vaccine construct for HIV infection.