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

Jamieson, P. J.; Shen, X.; Abu-Shmais, A. A.; Wasdin, P. T.; Janowska, K.; Edwards, R. J.; Scapellato, G.; Richardson, S. I.; Manamela, N. P.; Liu, S.; Barr, M.; Gillespie, R. A.; Mimms, J.; Suryadevara, N.; Sornberger, T. A.; Zost, S.; Parks, R.; Flaherty, S.; Janke, A. K.; Howard, B. N.; Suresh, Y. P.; Ruprecht, R. M.; Crowe, J. E.; Carnahan, R. H.; Bailey, J. R.; Masaru, K.; Haynes, B. F.; Moore, P. L.; Acharya, P.; Montefiori, D. C.; Kalams, S. A.; Lu, S.; Georgiev, I. S.

doi:10.1101/2025.01.17.633475

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bioRxiv · 10.1101/2025.01.17.633475

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

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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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Jamieson, P. J., Shen, X., Abu-Shmais, A. A., Wasdin, P. T., Janowska, K., Edwards, R. J., Scapellato, G., Richardson, S. I., Manamela, N. P., Liu, S., Barr, M., Gillespie, R. A., Mimms, J., Suryadevara, N., Sornberger, T. A., Zost, S., Parks, R., Flaherty, S., Janke, A. K., Howard, B. N., Suresh, Y. P., Ruprecht, R. M., Crowe, J. E., Carnahan, R. H., Bailey, J. R., Masaru, K., Haynes, B. F., Moore, P. L., Acharya, P., Montefiori, D. C., Kalams, S. A., Lu, S., Georgiev, I. S.. 2025-01-20. Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity. https://doi.org/10.1101/2025.01.17.633475

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