2. Academic Validation
  3. Long trimer-immunization interval and appropriate adjuvant reduce immune responses to the soluble HIV-1-envelope trimer base

Long trimer-immunization interval and appropriate adjuvant reduce immune responses to the soluble HIV-1-envelope trimer base

  • iScience. 2024 Jan 11;27(2):108877. doi: 10.1016/j.isci.2024.108877.
Hongying Duan 1,  Angela R Corrigan 1,  Cheng Cheng 1,  Andrea Biju 1,  Christopher A Gonelli 1,  Adam S Olia 1,  I-Ting Teng 1,  Kai Xu 1,  Sijy O'Dell 1,  Sandeep Narpala 1,  Mike Castro 1,  Leonid Serebryannyy 1,  Jennifer Wang 1,  Danealle K Parchment 1,  Edward K Sarfo 1,  Jelle van Schooten 2,  John-Paul Todd 1,  Shuishu Wang 1,  Darcy R Harris 1,  Hui Geng 1,  Alexander J Jafari 1,  VRC Production Program,  Ruth A Woodward 1,  Nicole A Doria-Rose 1,  Kathryn E Foulds 1,  Adrian B McDermott 1,  Marit J van Gils 2,  Richard A Koup 1,  Theodore C Pierson 1,  Peter D Kwong 1,  John R Mascola 1
Affiliations

Affiliations

  • 1 Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 2 Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam 1105AZ, the Netherlands.
PMID: 38318357 DOI: 10.1016/j.isci.2024.108877
Abstract

Soluble 'SOSIP'-stabilized HIV-1 envelope glycoprotein (Env) trimers elicit dominant antibody responses targeting their glycan-free base regions, potentially diminishing neutralizing responses. Previously, using a nonhuman primate model, we demonstrated that priming with fusion peptide (FP)-carrier conjugate immunogens followed by boosting with Env trimers reduced the anti-base response. Further, we demonstrated that longer immunization intervals further reduced anti-base responses and increased neutralization breadth. Here, we demonstrate that long trimer-boosting intervals, but not long FP immunization intervals, reduce the anti-base response. Additionally, we identify that FP priming before trimer immunization enhances antibody avidity to the Env trimer. We also establish that adjuvants Matrix M and Adjuplex further reduce anti-base responses and increase neutralizing titers. FP priming, long trimer-immunization interval, and an appropriate Adjuvant can thus reduce anti-base antibody responses and improve Env-directed vaccine outcomes.

Keywords

Immune response; Immunology; Virology.

Figures
Products