RV144 vaccine imprinting constrained HIV-1 evolution following breakthrough infection

Author:

Lewitus Eric12,Sanders-Buell Eric12,Bose Meera12,O’Sullivan Anne Marie12,Poltavee Kultida1,Li Yifan12ORCID,Bai Hongjun12ORCID,Mdluli Thembi12,Donofrio Gina12,Slike Bonnie12,Zhao Hong3,Wong Kim3,Chen Lennie3,Miller Shana12,Lee Jenica12,Ahani Bahar12,Lepore Steven12,Muhammad Sevan12,Grande Rebecca12,Tran Ursula12,Dussupt Vincent12,Mendez-Rivera Letzibeth12,Nitayaphan Sorachai4,Kaewkungwal Jaranit4,Pitisuttithum Punnee5,Rerks-Ngarm Supachai6,O’Connell Robert J4,Janes Holly7ORCID,Gilbert Peter B7,Gramzinski Robert1,Vasan Sandhya12,Robb Merlin L12,Michael Nelson L8,Krebs Shelly J12,Herbeck Joshua T9,Edlefsen Paul T7,Mullins James I3,Kim Jerome H1,Tovanabutra Sodsai12,Rolland Morgane12ORCID

Affiliation:

1. US Military HIV Research Program, WRAIR, Silver Spring, MD 20910, USA

2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD 20817, USA

3. Department of Microbiology, University of Washington, Seattle, WA 98195, USA

4. US Army Medical Directorate of the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

5. Mahidol University, Nakhon Pathom, Thailand

6. Thai Ministry of Public Health, Nonthaburi, Thailand

7. Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA

8. Center for Infectious Disease Research, WRAIR, Silver Spring, MD 20910, USA

9. Department of Global Health, University of Washington, Seattle, WA 98195, USA

Abstract

Abstract The scale of the HIV-1 epidemic underscores the need for a vaccine. The multitude of circulating HIV-1 strains together with HIV-1’s high evolvability hints that HIV-1 could adapt to a future vaccine. Here, we wanted to investigate the effect of vaccination on the evolution of the virus post-breakthrough infection. We analyzed 2,635 HIV-1 env sequences sampled up to a year post-diagnosis from 110 vaccine and placebo participants who became infected in the RV144 vaccine efficacy trial. We showed that the Env signature sites that were previously identified to distinguish vaccine and placebo participants were maintained over time. In addition, fewer sites were under diversifying selection in the vaccine group than in the placebo group. These results indicate that HIV-1 would possibly adapt to a vaccine upon its roll-out.

Funder

cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of the Army

Publisher

Oxford University Press (OUP)

Subject

Virology,Microbiology

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