Immunization with germ line–targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques
Ashley N. Nelson, Xiaoying Shen, Sravani Vekatayogi, Shiyu Zhang, Gabriel Ozorowski, Maria Dennis, Leigh M. Sewall, Emma C. Milligan, Dominique Davis, Kaitlyn Cross, Yue Chen, Jelle van Schooten, Joshua Eudailey, John E. Isaac, Saad Memon, Carolyn Weinbaum, Hongmei Gao, Sherry Stanfield-Oakley, Alliyah Byrd, Suni Chutkan, Stella J. Berendam, Kenneth Cronin, Anila Yasmeen, S. Munir Alam, Celia C. LaBranche, Kenneth A. Rogers, Lisa Shirreff, Albert Cupo, Ronald Derking, François 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
Abstract
Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage–designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41—named “SOS”—and an isoleucine-to-proline point mutation—named “IP”—at residue 559) to induce precursor CD4 binding site (CD4bs)–targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line–targeting BG505 SOSIP GT1.1 ( n = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants ( n = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage–designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.