Vaccination induces broadly neutralizing antibody precursors to HIV gp41

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1073-1082
Number of pages10
JournalNature Immunology
Volume25
Issue number6
DOIs
StatePublished - Jun 2024
Externally publishedYes

Fingerprint

Dive into the research topics of 'Vaccination induces broadly neutralizing antibody precursors to HIV gp41'. Together they form a unique fingerprint.

Cite this