Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119
Spyros A. Kalams, Barbara K. Felber, James I. Mullins, Hyman M. Scott, Mary A. Allen, Stephen C. De Rosa, Jack Heptinstall, Georgia D. Tomaras, Jiani Hu, Allan C. DeCamp, Margherita Rosati, Jenifer Bear, Michael N. Pensiero, John Eldridge, Michael A. Egan, Drew Hannaman, M. Juliana McElrath, George N. Pavlakis, HIV Vaccine Trials Network 119(HVTN 119) Study Team
Spyros A. Kalams, Barbara K. Felber, James I. Mullins, Hyman M. Scott, Mary A. Allen, Stephen C. De Rosa, Jack Heptinstall, Georgia D. Tomaras, Jiani Hu, Allan C. DeCamp, Margherita Rosati, Jenifer Bear, Michael N. Pensiero, John Eldridge, Michael A. Egan, Drew Hannaman, M. Juliana McElrath, George N. Pavlakis, HIV Vaccine Trials Network 119(HVTN 119) Study Team
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Clinical Research and Public Health AIDS/HIV Clinical trials

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

Abstract

BACKGROUND An HIV-1 DNA vaccine composed of 7 highly conserved, structurally important elements (conserved elements, CE) of p24Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. DNA vaccination of CE prime/CE+p55Gag boost was compared with p55Gag.METHODS Two groups (n = 25) received 4 DNA vaccinations (CE/CE+p55Gag or p55Gag) by intramuscular injection/electroporation, including IL-12 DNA adjuvant. The placebo group (n = 6) received saline. Participants were followed for safety and tolerability. Immunogenicity was assessed for T cell and antibody responses.RESULTS Both regimens were safe and generally well tolerated. The p24CE vaccine was immunogenic and significantly boosted by CE+p55Gag (64% CD4+, P = 0.037; 42% CD8+, P = 0.004). CE+p55Gag induced responses to 5 of 7 CE, compared with only 2 CE by p55Gag DNA, with a higher response to CE5 in 30% of individuals (P = 0.006). CE+p55Gag induced significantly higher CD4+ CE T cell breadth (0.68 vs. 0.22 CE; P = 0.029) and a strong trend for overall T cell breadth (1.14 vs. 0.52 CE; P = 0.051). Both groups developed high cellular and humoral responses. p24CE vaccine–induced CD4+ CE T cell responses correlated (P = 0.007) with p24Gag antibody responses.CONCLUSION The CE/CE+p55Gag DNA vaccine induced T cell responses to conserved regions in p24Gag, increasing breadth and epitope recognition throughout p55Gag compared with p55Gag DNA. Vaccines focusing immune responses by priming responses to highly conserved regions could be part of a comprehensive HIV vaccine strategy.TRIAL REGISTRATION Clinical Trials.gov NCT03181789FUNDING HVTN, NIAID/NIH

Authors

Spyros A. Kalams, Barbara K. Felber, James I. Mullins, Hyman M. Scott, Mary A. Allen, Stephen C. De Rosa, Jack Heptinstall, Georgia D. Tomaras, Jiani Hu, Allan C. DeCamp, Margherita Rosati, Jenifer Bear, Michael N. Pensiero, John Eldridge, Michael A. Egan, Drew Hannaman, M. Juliana McElrath, George N. Pavlakis, HIV Vaccine Trials Network 119(HVTN 119) Study Team

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Figure 6

T cell responses to the 3 proteolytic cleavage products p17Gag, p24Gag, and p15Gag derived from p55Gag.

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T cell responses to the 3 proteolytic cleavage products p17Gag, p24Gag, ...
Bar and line plots show T cell response rates (upper panels) and magnitudes (box-line plots, lower panels) at M1.5 and M6.5. IFN-γ+ p55Gag-specific CD4+ (A) and CD8+ (B) T cell responses to p17Gag, p24Gag, and p15Gag were measured at M1.5 and M6.5 in the T1 and T2 groups. Peptide pools comprised a mixture of 10-mer peptides overlapping by 9 AA spanning each protein. Response rates are given as the percentage of all vaccine recipients analyzed. Median response magnitudes are given in the panels as percentage of CD4+ and CD8+ T cells found in positive responders (see Methods).