Frontiers in Immunology (Jun 2020)
Harnessing Activin A Adjuvanticity to Promote Antibody Responses to BG505 HIV Envelope Trimers
- Diane G. Carnathan,
- Diane G. Carnathan,
- Diane G. Carnathan,
- Kirti Kaushik,
- Ali H. Ellebedy,
- Ali H. Ellebedy,
- Ali H. Ellebedy,
- Chiamaka A. Enemuo,
- Etse H. Gebru,
- Pallavi Dhadvai,
- Mohammed Ata Ur Rasheed,
- Mohammed Ata Ur Rasheed,
- Matthias G. Pauthner,
- Matthias G. Pauthner,
- Gabriel Ozorowski,
- Gabriel Ozorowski,
- Rafi Ahmed,
- Rafi Ahmed,
- Dennis R. Burton,
- Dennis R. Burton,
- Dennis R. Burton,
- Andrew B. Ward,
- Andrew B. Ward,
- Guido Silvestri,
- Guido Silvestri,
- Guido Silvestri,
- Shane Crotty,
- Shane Crotty,
- Shane Crotty,
- Michela Locci,
- Michela Locci,
- Michela Locci
Affiliations
- Diane G. Carnathan
- Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States
- Diane G. Carnathan
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Diane G. Carnathan
- Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, United States
- Kirti Kaushik
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Ali H. Ellebedy
- Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, United States
- Ali H. Ellebedy
- Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, United States
- Ali H. Ellebedy
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
- Chiamaka A. Enemuo
- Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States
- Etse H. Gebru
- Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States
- Pallavi Dhadvai
- Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States
- Mohammed Ata Ur Rasheed
- Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, United States
- Mohammed Ata Ur Rasheed
- Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, United States
- Matthias G. Pauthner
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Matthias G. Pauthner
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Gabriel Ozorowski
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Gabriel Ozorowski
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, United States
- Rafi Ahmed
- Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, United States
- Rafi Ahmed
- Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, United States
- Dennis R. Burton
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Dennis R. Burton
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United States
- Dennis R. Burton
- Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States
- Andrew B. Ward
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Andrew B. Ward
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, United States
- Guido Silvestri
- Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States
- Guido Silvestri
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Guido Silvestri
- Emory Vaccine Center, School of Medicine, Emory University, Atlanta, GA, United States
- Shane Crotty
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Shane Crotty
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Shane Crotty
- 0Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA, United States
- Michela Locci
- Scripps Center for HIV/AIDS Vaccine Immunogen Development (CHAVD), The Scripps Research Institute, La Jolla, CA, United States
- Michela Locci
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, United States
- Michela Locci
- 1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- DOI
- https://doi.org/10.3389/fimmu.2020.01213
- Journal volume & issue
-
Vol. 11
Abstract
T follicular helper (TFH) cells are powerful regulators of affinity matured long-lived plasma cells. Eliciting protective, long-lasting antibody responses to achieve persistent immunity is the goal of most successful vaccines. Thus, there is potential in manipulating TFH cell responses. Herein, we describe an HIV vaccine development approach exploiting the cytokine activin A to improve antibody responses against recombinant HIV Envelope (Env) trimers in non-human primates. Administration of activin A improved the magnitude of Env-specific antibodies over time and promoted a significant increase in Env-specific plasma cells in the bone marrow. The boost in antibody responses was associated with reduced frequencies of T follicular regulatory (TFR) cells and increased germinal center T follicular helper (GC-TFH) to TFR cell ratios. Overall, these findings suggest that adjuvants inducing activin A production could potentially be incorporated in future rational design vaccine strategies aimed at improving germinal centers, long-lived plasma cells, and sustained antibody responses.
Keywords
