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.

Antiretroviral therapy alone is insufficient in curing HIV-1 infection, due to latent viral reservoir persistency. Here, authors explore the post-virologic control of combining active and passive immunisation with vesatolimod, in a SHIV-infected rhesus macaque model.

Details

Title
Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques
Author
Walker-Sperling, Victoria E. K. 1 ; Mercado, Noe B. 1   VIAFID ORCID Logo  ; Chandrashekar, Abishek 1   VIAFID ORCID Logo  ; Borducchi, Erica N. 1 ; Liu, Jinyan 1 ; Nkolola, Joseph P. 1 ; Lewis, Mark 2   VIAFID ORCID Logo  ; Murry, Jeffrey P. 3 ; Yang, Yunling 3 ; Geleziunas, Romas 3 ; Robb, Merlin L. 4   VIAFID ORCID Logo  ; Michael, Nelson L. 4   VIAFID ORCID Logo  ; Pau, Maria G. 5 ; Wegmann, Frank 5   VIAFID ORCID Logo  ; Schuitemaker, Hanneke 5   VIAFID ORCID Logo  ; Fray, Emily J. 6 ; Kumar, Mithra R. 6 ; Siliciano, Janet D. 6 ; Siliciano, Robert F. 6 ; Barouch, Dan H. 7   VIAFID ORCID Logo 

 Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Boston, USA (GRID:grid.239395.7) (ISNI:0000 0000 9011 8547) 
 Bioqual, Rockville, USA (GRID:grid.282501.c) (ISNI:0000 0000 8739 6829) 
 Gilead Sciences, Foster City, USA (GRID:grid.418227.a) (ISNI:0000 0004 0402 1634) 
 Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166) 
 Janssen Vaccines & Prevention, Leiden, The Netherlands (GRID:grid.497529.4) (ISNI:0000 0004 0625 7026) 
 Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311) 
 Beth Israel Deaconess Medical Center, Center for Virology and Vaccine Research, Boston, USA (GRID:grid.239395.7) (ISNI:0000 0000 9011 8547); Ragon Institute of MGH, MIT, and Harvard, Cambridge, USA (GRID:grid.461656.6) (ISNI:0000 0004 0489 3491) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2677215205
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.