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. (9th November 2022)

• Record Type: Journal Article
• Authors: Stieh, Daniel J; Barouch, Dan H; Comeaux, Christy; Sarnecki, Michal; Stephenson, Kathryn E; Walsh, Stephen R; Sawant, Sheetal; Heptinstall, Jack; Tomaras, Georgia D; Kublin, James G; McElrath, M Juliana; Cohen, Kristen W; De Rosa, Stephen C; Alter, Galit; Ferrari, Guido; Montefiori, David; Mann, Philipp; Nijs, Steven; Callewaert, Katleen; Goepfert, Paul A; Edupuganti, Srilatha; Karita, Etienne; Seaman, Michael S; Corey, Lawrence; Baden, Lindsey R; Pau, Maria G; Schuitemaker, Hanneke; Tomaka, Frank
• Is Part Of: Journal of infectious diseases. Volume 227:Number 8(2023)
• Page Start: 939
• Page End: 950
• Publication Date: 2022-11-09
• Subjects: Ad26 HIV vaccine -- broad immunogenicity -- cross-clade -- heterologous regimen -- mosaic HIV antigen -- tetravalent; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiac445
• Languages: English
• ISSNs: 0022-1899

Abstract

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.