Cross-reactivity of HIV vaccine responses and the microbiomeWilliams, Wilton B.; Han, Qifeng; Haynes, Barton F.Current Opinion in HIV and AIDS: January 2018 - Volume 13 - Issue 1 - p 9–14 doi: 10.1097/COH.0000000000000423 THE MICROBIOME IN HIV: Edited by Alan L. Landay, James G. Kublin and Seema N. Desai Buy Abstract Author InformationAuthors Article MetricsMetrics Purpose of review A successful human immunodeficiency virus-type 1 (HIV-1) vaccine will require immunogens that induce protective immune responses. However, recent studies suggest that the response to HIV-1 and perhaps other viruses may be altered by immune system exposure to intestinal microbiota-antigens. This review will discuss select aspects of these studies. Recent findings Naïve CD4 T and B cell repertoires can be imprinted by intestinal microbiota-antigens to respond to virus epitopes prior to virus infection. A multiclade envelope (Env) gp145 DNA prime, recombinant adenovirus type 5 boost vaccine tested in a HIV Vaccine Trials Network (HVTN) phase IIb human vaccine efficacy trial (HVTN 505) induced a dominant gp41-reactive antibody response that was non-neutralizing and cross-reactive with intestinal microbiota. This vaccine regimen also induced a dominant gp41-reactive, intestinal microbiota-cross-reactive gp41 antibody response in neonatal and adult Rhesus macaques. Studies of naïve CD4 T cells have demonstrated cross-reactivity to both HIV-1 and influenza peptides. Summary HIV-1 Env vaccine-induced CD4 T and B cell responses can originate from a pool of intestinal microbiota-cross-reactive immune cells. Moreover, intestinal microbiota-cross-reactive HIV-1 Env antibodies are ineffective in protection against HIV-1 infection. Thus, intestinal microbiota-imprinting of the B cell repertoire may be one of several roadblocks to the induction of protective HIV-1 antibodies. Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA Correspondence to Wilton B. Williams and Barton F. Haynes, Duke University Medical Center, 2 Genome Court, MSRBII Bldg., Room 4090, DUMC 103020, Durham, NC 27710, USA. Tel: +1 919 684 5279; fax: +1 919 684 5230; e-mails: Wilton.email@example.com; firstname.lastname@example.org Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.