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 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, ASCENT/HVTN118/HPX2003 Study Team
Author Information
Daniel J Stieh: Janssen Vaccines and Prevention Leiden, the Netherlands.
Dan H Barouch: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Christy Comeaux: Janssen Vaccines and Prevention Leiden, the Netherlands.
Michal Sarnecki: Janssen Vaccines, Bern, Switzerland.
Kathryn E Stephenson: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Stephen R Walsh: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Sheetal Sawant: Department of Surgery, Center for Human Systems Immunology, and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Jack Heptinstall: Department of Surgery, Center for Human Systems Immunology, and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Georgia D Tomaras: Department of Surgery, Center for Human Systems Immunology, and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
James G Kublin: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
M Juliana McElrath: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Kristen W Cohen: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Stephen C De Rosa: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Galit Alter: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA. ORCID
Guido Ferrari: Department of Surgery, Center for Human Systems Immunology, and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
David Montefiori: Department of Surgery, Center for Human Systems Immunology, and Duke Human Vaccine Institute, Duke University, Durham, North Carolina, USA.
Philipp Mann: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Steven Nijs: Janssen Research and Development, Beerse, Belgium.
Katleen Callewaert: Janssen Research and Development, Beerse, Belgium.
Paul A Goepfert: Division of Infectious Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Srilatha Edupuganti: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Etienne Karita: Rwanda Zambia HIV Research Group, Kigali, Rwanda.
Michael S Seaman: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Lawrence Corey: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Lindsey R Baden: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Maria G Pau: Janssen Vaccines and Prevention Leiden, the Netherlands.
Hanneke Schuitemaker: Janssen Vaccines and Prevention Leiden, the Netherlands.
Frank Tomaka: Janssen Research and Development, Titusville, New Jersey, USA.
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.
