Journal Article

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

Hall, Breana, Kim, Jerome H., Juraska, Michal, Robb, Merlin L., Kublin, James, O’Connell, Robert J., Roederer, Mario, O'Sullivan, Annemarie, Edlefsen, Paul T., Bailer, Robert, Koup, Richard A., Hammer, Scott M., Gottardo, Raphael, Graham, Barney S., Dommaraju, Kalpana, Styrchak, Sheila, LePore, Steven, Bai, Hongjun, Chen, Lennie, Ahmed, Hasan, Corey, Lawrence, Mullins, James I., Sanders-Buell, Eric, Sobieszczyk, Magdalena E., Adams, Elizabeth, Michael, Nelson L., D’Souza, Patricia, Geraghty, Daniel E., Mascola, John R., Tomaras, Georgia D., deCamp, Allan C., Tovanabutra, Sodsai, Gilbert, Peter B., Poltavee, Kultida, Zhao, Hong, Goodman, Derrick, Miller, Shana, Fiore-Gartland, Andrew J., Rolland, Morgane, Carpp, Lindsay N., Bose, Meera, Frahm, Nicole, Karuna, Shelly T., Magaret, Craig A., Wong, Kim, Frenkel, Lisa, McElrath, M. Juliana, Tay, Matthew Z.

2017

Overview

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / AIDS / AIDS vaccines / Binding sites / Biology and Life Sciences / Cancer / CD4 antigen / Combined vaccines / Deoxyribonucleic acid / Disease prevention / DNA / Effectiveness / Gag protein / Gene mapping / Genetic aspects / Genomes / Glycoprotein gp120 / Glycoproteins / HIV / HIV infection / Human immunodeficiency virus / Immune response / Infections / Infectious diseases / Medical research / Medicine / Medicine and Health Sciences / Military medicine / Monoclonal antibodies / Physiological aspects / Prevention / Research and Analysis Methods / Sieve analysis / Vaccine efficacy / Vaccines / Viral proteins / Viruses