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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-021-00298-4 |
| _version_ | 1797428070925205504 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T08:52:49Z |
| format | Article |
| id | doaj.art-1a878c0b5f054d51810e80949b2527b7 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T08:52:49Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-1a878c0b5f054d51810e80949b2527b72023-12-02T13:42:53ZengNature Portfolionpj Vaccines2059-01052021-03-016111710.1038/s41541-021-00298-4Effects of persistent modulation of intestinal microbiota on SIV/HIV vaccination in rhesus macaquesNichole R. Klatt0Courtney Broedlow1Jessica M. Osborn2Andrew T. Gustin3Sandra Dross4Megan A. O’Connor5Ernesto Coronado6Philip Barnette7Tiffany Hensley-McBain8Alexander S. Zevin9Roshell Muir10Alexander Roederer11Solomon Wangari12Naoto Iwayama13Chul Y. Ahrens14Jeremy Smedley15Cassandra Moats16Rebecca M. Lynch17Elias K. Haddad18Nancy L. Haigwood19Deborah H. Fuller20Jennifer A. Manuzak21Department of Pharmaceutics, University of WashingtonDepartment of Pharmaceutics, University of WashingtonWashington National Primate Research Center, University of WashingtonDepartment of Pharmaceutics, University of WashingtonWashington National Primate Research Center, University of WashingtonWashington National Primate Research Center, University of WashingtonDepartment of Pharmaceutics, University of WashingtonOregon National Primate Research Center, Oregon Health and Science UniversityDepartment of Pharmaceutics, University of WashingtonDepartment of Pharmaceutics, University of WashingtonDivision of Infectious Diseases and HIV Medicine, Drexel University College of MedicineDepartment of Pharmaceutics, University of WashingtonWashington National Primate Research Center, University of WashingtonWashington National Primate Research Center, University of WashingtonWashington National Primate Research Center, University of WashingtonWashington National Primate Research Center, University of WashingtonWashington National Primate Research Center, University of WashingtonDepartment of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health SciencesDivision of Infectious Diseases and HIV Medicine, Drexel University College of MedicineOregon National Primate Research Center, Oregon Health and Science UniversityWashington National Primate Research Center, University of WashingtonDepartment of Pharmaceutics, University of WashingtonAbstract 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.https://doi.org/10.1038/s41541-021-00298-4 |
| spellingShingle | 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 npj Vaccines |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41541-021-00298-4 |
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