Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity

Kavli Affiliate: Robert Edwards

| Authors: Parker J. Jamieson, Xiaoying Shen, Alexandra A. Abu-Shmais, Perry T. Wasdin, Katarzyna Janowska, Robert J. Edwards, Garrett Scapellato, Simone I. Richardson, Nelia P. Manamela, Shuying Liu, Maggie Barr, Rebecca A. Gillespie, Jessica Mimms, Naveenchandra Suryadevara, Ty A. Sornberger, Seth Zost, Rob Parks, Shelby Flaherty, Alexis K. Janke, Bethany N. Howard, Yukthi P. Suresh, Ruth M. Ruprecht, James E. Crowe, Jr., Robert H. Carnahan, Justin R. Bailey, Kanekiyo Masaru, Barton F. Haynes, Penny L. Moore, Priyamvada Acharya, David C. Montefiori, Spyros A. Kalams, Shan Lu and Ivelin S. Georgiev

| Summary:

HIV-1 continues to pose a significant global health challenge, requiring ongoing research into effective prevention and treatment strategies. Understanding the B cell repertoire that can be engaged upon vaccination in humans is crucial for the development of future preventive vaccines. In this study, PBMCs from HIV-negative participants in the multivalent HVTN124 human HIV-1 vaccine clinical trial were interrogated for HIV-reactive B cells using LIBRA-seq, a high-throughput B cell mapping technology. We report the discovery of glycan-reactive antibodies capable of neutralizing diverse heterologous HIV-1 virus strains. Further, isolated antibodies showed broad cross-reactivity against antigens from a variety of other pathogens, while remaining mostly negative on autoreactivity assays. The emerging class of glycan-reactive virus-neutralizing antibodies with exceptional breadth of pathogen cross-reactivity may present an effective target for vaccination at the population level.

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