학술논문
Long trimer-immunization interval and appropriate adjuvant reduce immune responses to the soluble HIV-1-envelope trimer base
Document Type
article
Author
Hongying Duan; Angela R. Corrigan; Cheng Cheng; Andrea Biju; Christopher A. Gonelli; Adam S. Olia; I-Ting Teng; Kai Xu; Sijy O’Dell; Sandeep Narpala; Mike Castro; Leonid Serebryannyy; Jennifer Wang; Danealle K. Parchment; Edward K. Sarfo; Jelle van Schooten; John-Paul Todd; Shuishu Wang; Darcy R. Harris; Hui Geng; Alexander J. Jafari; Ruth A. Woodward; Nicole A. Doria-Rose; Kathryn E. Foulds; Adrian B. McDermott; Marit J. van Gils; Richard A. Koup; Theodore C. Pierson; Peter D. Kwong; John R. Mascola
Source
iScience, Vol 27, Iss 2, Pp 108877- (2024)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: 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.