Vaccination induces broadly neutralizing antibody precursors to HIV gp41

Schiffner, Torben; Phung, Ivy; Ray, Rashmi; Irimia, Adriana; Tian, Ming; Swanson, Olivia; Lee, Jeong Hyun; Lee, Chang-Chun D.; Marina-Zárate, Ester; Cho, So Yeon; Huang, Jiachen; Ozorowski, Gabriel; Skog, Patrick D.; Serra, Andreia M.; Rantalainen, Kimmo; Allen, Joel D.; Baboo, Sabyasachi; Rodriguez, Oscar L.; Himansu, Sunny; Zhou, Jianfu; Hurtado, Jonathan; Flynn, Claudia T.; McKenney, Katherine; Havenar-Daughton, Colin; Saha, Swati; Shields, Kaitlyn; Schultze, Steven; Smith, Melissa L.; Liang, Chi-Hui; Toy, Laura; Pecetta, Simone; Lin, Ying-Cing; Willis, Jordan R.; Sesterhenn, Fabian; Kulp, Daniel W.; Hu, Xiaozhen; Cottrell, Christopher A.; Zhou, Xiaoya; Ruiz, Jennifer; Wang, Xuesong; Nair, Usha; Kirsch, Kathrin H.; Cheng, Hwei-Ling; Davis, Jillian; Kalyuzhniy, Oleksandr; Liguori, Alessia; Diedrich, Jolene K.; Ngo, Julia T.; Lewis, Vanessa; Phelps, Nicole; Tingle, Ryan D.; Spencer, Skye; Georgeson, Erik; Adachi, Yumiko; Kubitz, Michael; Eskandarzadeh, Saman; Elsliger, Marc A.; Amara, Rama R.; Landais, Elise; Briney, Bryan; Burton, Dennis R.; Carnathan, Diane G.; Silvestri, Guido; Watson, Corey T.; Yates, John R.; Paulson, James C.; Crispin, Max; Grigoryan, Gevorg; Ward, Andrew B.; Sok, Devin; Alt, Frederick W.; Wilson, Ian A.; Batista, Facundo D.; Crotty, Shane; Schief, William R.

doi:10.1038/s41590-024-01833-w

Title: Vaccination induces broadly neutralizing antibody precursors to HIV gp41

Journal Article · Thu May 30 00:00:00 UTC 2024 · Nature Immunology

DOI: https://doi.org/10.1038/s41590-024-01833-w · OSTI ID:2470208

Schiffner, Torben ^[1];

; Ray, Rashmi; Irimia, Adriana; Tian, Ming;

; Lee, Jeong Hyun;

;

; Cho, So Yeon; Huang, Jiachen;

; Skog, Patrick D.; Serra, Andreia M.;

;

; Zhou, Jianfu more »

The Scripps Research Institute, La Jolla, CA (United States); Leipzig University (Germany); et al.

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Bill & Melinda Gates Foundation; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470208

Journal Information:: Nature Immunology, Journal Name: Nature Immunology Journal Issue: 6 Vol. 25; ISSN 1529-2908

Publisher:: Nature Research, Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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