Preferential engagement of the anti-inflammatory ATP/adenosine axis by HIV vaccine candidate with V1-deleted envelope in male rhesus macaques

Authors

• Isabela Silva de Castro, National Cancer Institute, Bethesda, MD
• Mohammad Arif Rahman, National Cancer Institute, Bethesda, MD
• Massimiliano Bissa, National Cancer Institute, Bethesda, MD
• Katherine C. Goldfarbmuren, Leidos Biomedical Research, Inc., Frederick, MD
• Luca Schifanella, National Cancer Institute, Bethesda, MD
• Sarkis Sarkis, National Cancer Institute, Bethesda, MD
• Kombo F. N’guessan, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD
• Zhong Min Ma, University of California Davis, Davis, CA
• Anna Gutowska, National Cancer Institute, Bethesda, MD
• James D. Stamos, National Cancer Institute, Bethesda, MD
• Melvin N. Doster, National Cancer Institute, Bethesda, MD
• Emmanuel K. Woode, National Cancer Institute, Bethesda, MD
• Justin C. Smith, LSU Health Sciences Center - New OrleansFollow
• Pamela A. Kozlowski, LSU Health Sciences Center - New OrleansFollow
• LaTonya D. Williams, Duke University, Durham, NC
• Katherine M. McKinnon, National Cancer Institute, Bethesda, MD
• Georgia D. Tomaras, Duke University, Durham, NC
• Xiaoying Shen, Duke University, Durham, NC
• David C. Montefiori, Duke University, Durham, NC
• Sampa Santra, Boston Children's Hospital, Boston, MA
• Dominic Paquin-Proulx, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD
• Frank Maldarelli, National Cancer Institute, Bethesda, MD
• Timothy Cardozo, New York University, New York, NY
• Genoveffa Franchini, National Cancer Institute, Bethesda, MD

Document Type

Article

Publication Date

9-15-2026

Publication Title

Cell Reports Medicine

Abstract

We evaluate the efficacy and immunogenicity of HIV clade A/E A244 envelope (Env) immunogens with the 23 amino acids of variable region 1 deleted (ΔV1) or retained (wild-type [WT]) in macaques. Only the ΔV1 regimen significantly reduces the risk of mucosal acquisition of clade C simian/human immunodeficiency virus (SHIV) 1157(QNE)Y173H versus controls, providing 81% efficacy and leaving 10 of 12 immunized animals uninfected. ΔV1 vaccination induces higher systemic antibody-dependent cellular cytotoxicity (ADCC) targeting helical-V2 and anti-inflammatory myeloid cells, which, together with IL-17 + NKp44 + innate lymphoid cells (ILCs) and systemic PD-1 + helper T cells, correlated with reduced infection risk. By contrast, WT immunization induces higher IL-15, CCR2 + pDC, and gp70/V1V2-biased responses, which, along with mucosal IFN-γ + NKG2A − NKp44 − ILCs, were associated with increased susceptibility. Ex vivo , ΔV1 gp120 reduced CCR5 expression on CD4 + T cells relative to WT gp120, consistent with the anti-inflammatory mucosal response by ΔV1-vaccine regimens in vivo . Thus, V1 deletion promotes an anti-inflammatory mucosal landscape less permissive to HIV seeding and dissemination following virus exposure.

PubMed ID

42685700

Volume

7

Issue

9

Publisher

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Silva de Castro, Isabela; Rahman, Mohammad Arif; Bissa, Massimiliano; Goldfarbmuren, Katherine C.; Schifanella, Luca; Sarkis, Sarkis; N’guessan, Kombo F.; Ma, Zhong Min; Gutowska, Anna; Stamos, James D.; Doster, Melvin N.; Woode, Emmanuel K.; Smith, Justin C.; Kozlowski, Pamela A.; Williams, LaTonya D.; McKinnon, Katherine M.; Tomaras, Georgia D.; Shen, Xiaoying; Montefiori, David C.; Santra, Sampa; Paquin-Proulx, Dominic; Maldarelli, Frank; Cardozo, Timothy; and Franchini, Genoveffa, "Preferential engagement of the anti-inflammatory ATP/adenosine axis by HIV vaccine candidate with V1-deleted envelope in male rhesus macaques" (2026). School of Graduate Studies Faculty Publications. 673.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/673
10.1016/j.xcrm.2026.103022