T cell responses generated by HIV vaccines in clinical trials

Here we summarize evaluations of T cell immune responses in HIV vaccine clinical trials, highlighting investigations addressing optimization and validation of assays, reagents for determining multiclade HIV-specific responses, and current findings in phase I and II clinical testing.

Maintaining peripheral blood mononuclear cell quality and function is critical for optimal detection of T cell responses. Two recent reports emphasize the necessity for processing and freezing peripheral blood mononuclear cell within 8-12 h of venipuncture at local processing sites. Analytical designs of HIV peptide panels for use in T cell assays permit standardization of measurements between vaccines and laboratories, and evaluation of responses representing global HIV-1 strains. Phase I trials indicate superior induction of T cell response frequencies and magnitude using recombinant DNA and adenovirus serotype 5 (Ad5) vaccine with HIV-1 gene inserts. Additionally, use of a unique adjuvant with a recombinant Nef/Tat/gp120 vaccine induced high titer anti-HIV neutralizing antibodies, T cell proliferation, but not CD8 T cell responses.

T cell functional assays have achieved the standardization and validation to support licensure of vaccine candidates. Studies in progress will determine if these measurements are critical in defining correlates of immune protection.