Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques

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...

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Autores principales: Nichole R. Klatt, Courtney Broedlow, Jessica M. Osborn, Andrew T. Gustin, Sandra Dross, Megan A. O’Connor, Ernesto Coronado, Philip Barnette, Tiffany Hensley-McBain, Alexander S. Zevin, Roshell Muir, Alexander Roederer, Solomon Wangari, Naoto Iwayama, Chul Y. Ahrens, Jeremy Smedley, Cassandra Moats, Rebecca M. Lynch, Elias K. Haddad, Nancy L. Haigwood, Deborah H. Fuller, Jennifer A. Manuzak
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:1a878c0b5f054d51810e80949b2527b72021-12-02T15:52:58ZEffects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques10.1038/s41541-021-00298-42059-0105https://doaj.org/article/1a878c0b5f054d51810e80949b2527b72021-03-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00298-4https://doaj.org/toc/2059-0105Abstract 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™ adjuvant, while receiving daily oral Visbiome® 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.Nichole R. KlattCourtney BroedlowJessica M. OsbornAndrew T. GustinSandra DrossMegan A. O’ConnorErnesto CoronadoPhilip BarnetteTiffany Hensley-McBainAlexander S. ZevinRoshell MuirAlexander RoedererSolomon WangariNaoto IwayamaChul Y. AhrensJeremy SmedleyCassandra MoatsRebecca M. LynchElias K. HaddadNancy L. HaigwoodDeborah H. FullerJennifer A. ManuzakNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-17 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Nichole R. Klatt
Courtney Broedlow
Jessica M. Osborn
Andrew T. Gustin
Sandra Dross
Megan A. O’Connor
Ernesto Coronado
Philip Barnette
Tiffany Hensley-McBain
Alexander S. Zevin
Roshell Muir
Alexander Roederer
Solomon Wangari
Naoto Iwayama
Chul Y. Ahrens
Jeremy Smedley
Cassandra Moats
Rebecca M. Lynch
Elias K. Haddad
Nancy L. Haigwood
Deborah H. Fuller
Jennifer A. Manuzak
Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
description 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™ adjuvant, while receiving daily oral Visbiome® 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.
format article
author Nichole R. Klatt
Courtney Broedlow
Jessica M. Osborn
Andrew T. Gustin
Sandra Dross
Megan A. O’Connor
Ernesto Coronado
Philip Barnette
Tiffany Hensley-McBain
Alexander S. Zevin
Roshell Muir
Alexander Roederer
Solomon Wangari
Naoto Iwayama
Chul Y. Ahrens
Jeremy Smedley
Cassandra Moats
Rebecca M. Lynch
Elias K. Haddad
Nancy L. Haigwood
Deborah H. Fuller
Jennifer A. Manuzak
author_facet Nichole R. Klatt
Courtney Broedlow
Jessica M. Osborn
Andrew T. Gustin
Sandra Dross
Megan A. O’Connor
Ernesto Coronado
Philip Barnette
Tiffany Hensley-McBain
Alexander S. Zevin
Roshell Muir
Alexander Roederer
Solomon Wangari
Naoto Iwayama
Chul Y. Ahrens
Jeremy Smedley
Cassandra Moats
Rebecca M. Lynch
Elias K. Haddad
Nancy L. Haigwood
Deborah H. Fuller
Jennifer A. Manuzak
author_sort Nichole R. Klatt
title Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
title_short Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
title_full Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
title_fullStr Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
title_full_unstemmed Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaques
title_sort effects of persistent modulation of intestinal microbiota on siv/hiv vaccination in rhesus macaques
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1a878c0b5f054d51810e80949b2527b7
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