Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults: A Phase 1/2a Study
Daniel J Stieh, Dan H. Barouch, Christy Comeaux, Michal Sarnecki, Kathryn E. Stephenson, Stephen R. Walsh, Sheetal Sawant, Jack Heptinstall, Georgia D. Tomaras, James G. Kublin, M. Juliana McElrath, Kristen W. Cohen, Stephen C. De Rosa, Galit Alter, Guido Ferrari, David C. Montefiori, Philipp Mann, Steven Nijs, Katleen Callewaert, Paul Goepfert, Srilatha Edupuganti, Etienne Karita, Michael S. Seaman, Lawrence Corey, Lindsey R. Baden, Maria Grazia Pau, Hanneke Schuitemaker, Frank Tomaka, the ASCENT/HVTN118/HPX2003 Study Team, Julie A. Ake, Susan Buchbinder, Trevor A. Crowell, Zelda Euler, Ian Frank, Dimitri Goedhart, Jennifer Johnson, Michael C. Keefer, Colleen F. Kelley, Kenneth H. Mayer, Joseph P. Nkolola, Lauren Peter, Merlin L. Robb, Nadine Rouphael, Lorenz Scheppler, Magda Sobieszczyk, Hong‐Van Tieu, Matthew H. Collins, Varun K. Phadke
Abstract
BACKGROUND: Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV. METHODS: This placebo-controlled, double-blind, phase 1/2a study enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade C regimen plus mosaic gp140), or placebo. Primary end points were safety and antibody responses. RESULTS: In total 152/155 participants (clade C, n = 26; bivalent protein, n = 103; placebo, n = 26) received ≥1 injection. The highest adverse event (AE) severity was grade 3 (local pain/tenderness, 12%, 2%, and 0% of the respective groups; solicited systemic AEs, 19%, 15%, 0%). HIV-1 mosaic gp140-binding antibody titers were 79 595 ELISA units (EU)/mL and 137 520 EU/mL in the clade C and bivalent protein groups (P < .001) after dose 4 and 16 862 EU/mL and 25 162 EU/mL 6 months later. Antibody response breadth against clade C gp140 and clade C/non-clade C gp120 was highest in the bivalent protein group. CONCLUSIONS: Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses. Clinical Trials Registration. NCT02935686.