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

Autor: 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, Montefiori, Philipp, Mann, Steven, Nijs, Katleen, Callewaert, Paul A, Goepfert, Srilatha, Edupuganti, Etienne, Karita, Michael S, Seaman, Lawrence, Corey, Lindsey R, Baden, Maria G, Pau, Hanneke, Schuitemaker, Frank, Tomaka
Rok vydání: 2022
Předmět:
Zdroj: The Journal of infectious diseases.
ISSN: 1537-6613
0293-5686
Popis: 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.
Databáze: OpenAIRE
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