Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy

Boris Julg*, Kathryn E. Stephenson, Frank Tomaka, Stephen R. Walsh, C. Sabrina Tan, Ludo Lavreys, Michal Sarnecki, Jessica L. Ansel, Diane G. Kanjilal, Kate Jaegle, Tessa Speidel, Joseph P. Nkolola, Erica N. Borducchi, Esmee Braams, Laura Pattacini, Eleanor Burgess, Shlomi Ilan, Yannic Bartsch, Katherine E. Yanosick, Michael S. SeamanDaniel J. Stieh, Janine van Duijn, Wouter Willems, Merlin L. Robb, Nelson L. Michael, Bruce D. Walker, Maria Grazia Pau, Hanneke Schuitemaker, Dan H. Barouch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.

Original languageEnglish
Article number89
Journalnpj Vaccines
Issue number1
StatePublished - Dec 2024
Externally publishedYes


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