Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
Authors: Philip Barnette
Alexander Roederer
Solomon Wangari
Tiffany Hensley-McBain
Courtney Broedlow
Nancy L Haigwood
Nichole R Klatt
Alexander S Zevin
Sandra Dross
Jennifer A Manuzak
Elias K Haddad
Jeremy Smedley
Rebecca M Lynch
Jessica M Osborn
Andrew T Gustin
Roshell Muir
Megan A O&#x27;Connor
Chul Y Ahrens
Cassandra Moats
Naoto Iwayama
Deborah H Fuller
Ernesto Coronado
Journal: NPJ vaccines (2021)
Discipline: IMMUNOLOGY
Keywords: HIV transmission; microbiome; probiotic therapy; mucosal immunity; SIV/HIV vaccination
Affiliations: Department of Pharmaceutics, University of Washington, Seattle, WA, USA. ., Washington National Primate Research Center, University of Washington, Seattle, WA, USA. ., Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, FL, USA. ., Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA. ., Department of Pharmaceutics, University of Washington, Seattle, WA, USA., Washington National Primate Research Center, University of Washington, Seattle, WA, USA., Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA., Department of Microbiology, University of Washington, Seattle, WA, USA., Department of Immunology, University of Washington, Seattle, WA, USA., Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR, USA., Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, USA., Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA., Tulane National Primate Research Center, Tulane University, Covington, LA, USA. .

Abstract:  An effective vaccine to prevent HIV transmission has not yet been achieved. Modulation of the microbiome via probiotic therapy has been suggested to result in enhanced mucosal immunity. Here, we evaluated whether probiotic therapy could improve the immunogenicity and protective efficacy of SIV/HIV vaccination. Rhesus macaques were co-immunized with an SIV/HIV DNA vaccine via particle-mediated epidermal delivery and an HIV protein vaccine administered intramuscularly with Adjuplex‚Ñ?adjuvant, while receiving daily oral Visbiome¬Æ probiotics. Probiotic therapy alone led to reduced frequencies of colonic CCR5+ and CCR6+ CD4+ T cells. Probiotics with SIV/HIV vaccination led to similar reductions in colonic CCR5+ CD4+ T cell frequencies. SIV/HIV-specific T cell and antibody responses were readily detected in the periphery of vaccinated animals but were not enhanced with probiotic treatment. Combination probiotics and vaccination did not impact rectal SIV/HIV target populations or reduce the rate of heterologous SHIV acquisition during the intrarectal challenge. Finally, post-infection viral kinetics were similar between all groups. Thus, although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses. 

Retracted: No

PubPeer comments:
 It would have been nice to see the controls on the pre-infection figures as well for comparison. Interesting study. ,