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

Publication ,  Journal Article
Nelson, AN; Shen, X; Vekatayogi, S; Zhang, S; Ozorowski, G; Dennis, M; Sewall, LM; Milligan, E; Davis, D; Cross, KA; Chen, Y; van Schooten, J ...
Published in: bioRxiv
November 11, 2023

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.

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Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

November 11, 2023

Location

United States
 

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Chicago
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Nelson, A. N., Shen, X., Vekatayogi, S., Zhang, S., Ozorowski, G., Dennis, M., … Permar, S. R. (2023). Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques. BioRxiv. https://doi.org/10.1101/2023.11.07.565306
Nelson, Ashley N., Xiaoying Shen, Sravani Vekatayogi, Shiyu Zhang, Gabriel Ozorowski, Maria Dennis, Leigh M. Sewall, et al. “Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.BioRxiv, November 11, 2023. https://doi.org/10.1101/2023.11.07.565306.
Nelson AN, Shen X, Vekatayogi S, Zhang S, Ozorowski G, Dennis M, et al. Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques. bioRxiv. 2023 Nov 11;
Nelson AN, Shen X, Vekatayogi S, Zhang S, Ozorowski G, Dennis M, Sewall LM, Milligan E, Davis D, Cross KA, Chen Y, van Schooten J, Eudailey J, Isaac J, Memon S, Weinbaum C, Stanfield-Oakley S, Byrd A, Chutkan S, Berendam S, Cronin K, Yasmeen A, Alam SM, LaBranche CC, Rogers K, Shirreff L, Cupo A, Derking R, Villinger F, Klasse PJ, Ferrari G, Williams WB, Hudgens MG, Ward AB, Montefiori DC, Van Rompay KKA, Wiehe K, Moore JP, Sanders RW, De Paris K, Permar SR. Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques. bioRxiv. 2023 Nov 11;

Published In

bioRxiv

DOI

EISSN

2692-8205

Publication Date

November 11, 2023

Location

United States