AUTHOR=Carnathan Diane G. , Kaushik Kirti , Ellebedy Ali H. , Enemuo Chiamaka A. , Gebru Etse H. , Dhadvai Pallavi , Rasheed Mohammed Ata Ur , Pauthner Matthias G. , Ozorowski Gabriel , Ahmed Rafi , Burton Dennis R. , Ward Andrew B. , Silvestri Guido , Crotty Shane , Locci Michela 

TITLE=Harnessing Activin A Adjuvanticity to Promote Antibody Responses to BG505 HIV Envelope Trimers

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01213

DOI=10.3389/fimmu.2020.01213

ISSN=1664-3224

ABSTRACT=<p>T follicular helper (T<sub>FH</sub>) 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 T<sub>FH</sub> 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 (T<sub>FR</sub>) cells and increased germinal center T follicular helper (GC-T<sub>FH</sub>) to T<sub>FR</sub> 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.</p>