Article
作者: Goedhart, Dimitri ; Robb, Merlin L ; Kelley, Colleen F ; Tomaka, Frank ; Sawant, Sheetal ; Van Tieu, Hong ; Schuitemaker, Hanneke ; Peter, Lauren ; Stieh, Daniel J ; Goepfert, Paul A ; Baden, Lindsey R ; Johnson, Jennifer A ; Heptinstall, Jack ; Frank, Ian ; Edupuganti, Srilatha ; Rouphael, Nadine ; Tomaras, Georgia D ; Nkolola, Joseph ; Euler, Zelda ; Sobieszczyk, Magda ; Comeaux, Christy ; McElrath, M Juliana ; Buchbinder, Susan ; Crowell, Trevor A ; Sarnecki, Michal ; Stephenson, Kathryn E ; Alter, Galit ; Karita, Etienne ; Barouch, Dan H ; Ferrari, Guido ; Pau, Maria G ; Phadke, Varun K ; Keefer, Michael ; Walsh, Stephen R ; Cohen, Kristen W ; De Rosa, Stephen C ; Corey, Lawrence ; Kublin, James G ; Callewaert, Katleen ; Ake, Julie A ; Mayer, Kenneth H ; Mann, Philipp ; Collins, Matthew H ; Montefiori, David ; Scheppler, Lorenz ; Seaman, Michael S ; Nijs, Steven
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.
