Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

Abstract

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

• Authors: Ashley N Nelson, Xiaoying Shen, Sravani Vekatayogi, Shiyu Zhang, Gabriel Ozorowski, Maria Dennis, Leigh M Sewall, Emma Milligan, Dominique Davis, Kaitlyn A Cross, Yue Chen, Jelle van Schooten, Joshua Eudailey, John Isaac, Saad Memon, Carolyn Weinbaum, Sherry Stanfield-Oakley, Alliyah Byrd, Suni Chutkan, Stella Berendam, Kenneth Cronin, Anila Yasmeen, S Munir Alam, Celia C LaBranche, Kenneth Rogers, Lisa Shirreff, Albert Cupo, Ronald Derking, Francois Villinger, Per Johan Klasse, Guido Ferrari, Wilton B Williams, Michael G Hudgens, Andrew B Ward, David C Montefiori, Koen K A Van Rompay, Kevin Wiehe, John P Moore, Rogier W Sanders, Kristina De Paris, Sallie R Permar
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Nov 11 2023) United States
• PMID: 37986885 (Publication Type: Preprint)