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

Parker J. Jamieson; Xiaoying Shen; Alexandra A. Abu-Shmais; Perry T. Wasdin; Katarzyna Janowska; Robert J. Edwards; Garrett Scapellato; Maurice Bukenya; Lindsay E Bass; Simone I. Richardson; Nelia P. Manamela; Shuying Liu; Maggie Barr; Lindsey Adams; Cristina Paola Velez-Castro; Caitlin McCarthy; Caroline A. Alexander; Rebecca A. Gillespie; Jessica L. Mimms; Naveenchandra Suryadevara; Ty A. Sornberger; Seth J. Zost; Robert Parks; Shelby Flaherty; Alexis K. Janke; Bethany N. Howard; Yukthi P. Suresh; Ruth M. Ruprecht; James E. Crowe; Robert H. Carnahan

doi:10.1128/jvi.01256-25

ImmunologyJournal of VirologyNov 10, 2025

Peer-reviewed journal article

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

Parker J. Jamieson iD, Xiaoying Shen iD, Alexandra A. Abu-Shmais iD, Perry T. Wasdin iD, Katarzyna Janowska iD, Robert J. Edwards iD, Garrett Scapellato, Maurice Bukenya iD, Lindsay E Bass iD, Simone I. Richardson iD, Nelia P. Manamela iD, Shuying Liu iD, Maggie Barr iD, Lindsey Adams, Cristina Paola Velez-Castro, Caitlin McCarthy, Caroline A. Alexander iD, Rebecca A. Gillespie iD, Jessica L. Mimms, Naveenchandra Suryadevara iD, Ty A. Sornberger iD, Seth J. Zost iD, Robert Parks iD, Shelby Flaherty iD, Alexis K. Janke iD, , Ivelin S. Georgiev iD

Abstract

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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