Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

Victoria E. K. Walker-Sperling, Noe B. Mercado, Abishek Chandrashekar, Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Mark Lewis, Jeffrey P. Murry, Yunling Yang, Romas Geleziunas, Merlin L. Robb, Nelson L. Michael, Maria G. Pau, Frank Wegmann, Hanneke Schuitemaker, Emily J. Fray, Mithra R. Kumar, Janet D. Siliciano, Robert F. Siliciano and Dan H. Barouch ()
Additional contact information
Victoria E. K. Walker-Sperling: Beth Israel Deaconess Medical Center
Noe B. Mercado: Beth Israel Deaconess Medical Center
Abishek Chandrashekar: Beth Israel Deaconess Medical Center
Erica N. Borducchi: Beth Israel Deaconess Medical Center
Jinyan Liu: Beth Israel Deaconess Medical Center
Joseph P. Nkolola: Beth Israel Deaconess Medical Center
Mark Lewis: Bioqual
Jeffrey P. Murry: Gilead Sciences
Yunling Yang: Gilead Sciences
Romas Geleziunas: Gilead Sciences
Merlin L. Robb: Walter Reed Army Institute of Research
Nelson L. Michael: Walter Reed Army Institute of Research
Maria G. Pau: Janssen Vaccines & Prevention
Frank Wegmann: Janssen Vaccines & Prevention
Hanneke Schuitemaker: Janssen Vaccines & Prevention
Emily J. Fray: Johns Hopkins University School of Medicine
Mithra R. Kumar: Johns Hopkins University School of Medicine
Janet D. Siliciano: Johns Hopkins University School of Medicine
Robert F. Siliciano: Johns Hopkins University School of Medicine
Dan H. Barouch: Beth Israel Deaconess Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

Date: 2022
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DOI: 10.1038/s41467-022-31196-5

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