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The molecular immune modulator adenosine deaminase-1 enhances HIV specific humoral and cellular responses to a native-like HIV envelope trimer DNA vaccine
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The molecular immune modulator adenosine deaminase-1 enhances HIV specific humoral and cellular responses to a native-like HIV envelope trimer DNA vaccine

Michele A Kutzler, Gina Cusimano, David Joyner, Emily Konopka, Roshell Muir, Philip Barnette, Melanie Guderian, Iván Del Moral-Sánchez, Ronald Derking, Tom Bijl, …
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22 Apr 2024
DOI: https://doi.org/10.21203/rs.3.rs-4139764/v1
PMID: 38746176
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092827View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open
url
https://doi.org/10.21203/rs.3.rs-4139764/v1View
Published, Version of Record (VoR) Open

Abstract

There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines. We have previously demonstrated that adenosine deaminase-1 (ADA-1) is critical to the T follicular helper (TFH) function and improves vaccine immune responses . In this study, we demonstrate that co-delivery of plasmid-encoded adenosine deaminase 1 (pADA) with pBG505-TTT enhances the magnitude, durability, isotype switching and functionality of HIV-specific antibodies in a dose-sparing manner. Co-delivery of the molecular immune modulator ADA-1 also enhances HIV-specific T cell polyfunctionality, activation, and degranulation as well as memory B cell responses. These data demonstrate that pADA enhances HIV-specific cellular and humoral immunity, making ADA-1 a promising immune modulator for HIV-targeting vaccines.

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