Immunization with germ line–targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques

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 (<i>n</i> = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants (<i>n</i> = 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.

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Publication Details

Journal
Science Immunology
Published
2024-08-30
DOI
https://doi.org/10.1126/sciimmunol.adm7097
Citations
18
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
5.29

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article

Immunization with germ line–targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques

David C. Montefiori, Emma C. Milligan, Kenneth Cronin, John P. Moore et al.
18 citations
Science Immunology
HIV Research and Treatment
5.29
article

Immunization with germ line–targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques

David C. Montefiori, Emma C. Milligan, Kenneth Cronin, John P. Moore, Joshua Eudailey, Stella J. Berendam, S. Munir Alam, Kenneth A. Rogers, Maria Dennis, Anila Yasmeen, François Villinger, Kaitlyn Cross, Albert Cupo, Gabriel Ozorowski, Per Johan Klasse, Guido Ferrari, Sherry Stanfield-Oakley, Ronald Derking, Xiaoying Shen, Celia C. LaBranche, Sallie R. Permar, Kevin J. Wiehe, Kristina De Paris, Lisa Shirreff, Hongmei Gao, Alliyah Byrd, Andrew B. Ward, Carolyn Weinbaum, Ashley N. Nelson, Yue Chen, John E. Isaac, Michael G. Hudgens, Dominique Davis, Jelle van Schooten, Koen K. A. Van Rompay, Wilton B. Williams, Rogier W. Sanders, Shiyu Zhang, Leigh M. Sewall, Suni Chutkan, Saad Memon, Sravani Vekatayogi
article en
18 citations

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 (<i>n</i> = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants (<i>n</i> = 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.

Science ImmunologyVol. 9(98)
University of North Carolina at Chapel Hill (US), Scripps Research Institute (US), Cornell University (US), Amsterdam UMC Location University of Amsterdam (NL), Duke Medical Center (US), Weill Cornell Medicine (US), University of Louisiana at Lafayette (US), University of California, Davis (US)
Amsterdam University Medical Centers, China Scholarship Council, National Institutes of Health, Weill Cornell Medical College, University of California, Davis, Center for AIDS Research, University of Washington, University of North Carolina at Chapel Hill, National Institute of Allergy and Infectious Diseases, California National Primate Research Center, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Good health and well-being
Openalex Percentile: Top 4%
HIV Research and Treatment
5.29
DOIOpen Access PDFOpenAlex
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