Rapid elicitation of a new class of neutralizing N332-glycan independent V3-glycan antibodies against HIV-1 in nonhuman primates.

Relano-Rodriguez, I.; Du, J.; Lin, Z. J.; Kerwin, M.; Tarquis-Medina, M.; Urbano, E.; Cui, J.; Watkins, M.; Zhao, P.; Habib, R.; Gosh, S.; Park, J.; Boroughs, C.; Walsh, A. A.; Melo, M. B.; Shaw, G. M.; Hahn, B. H.; Irvine, D. J.; Wells, L.; Weiner, D. B.; Kulp, D. W.; Veazey, R. S.; Pallesen, J.; Escolano, A.

doi:10.1101/2025.09.04.674340

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bioRxiv · 10.1101/2025.09.04.674340

Rapid elicitation of a new class of neutralizing N332-glycan independent V3-glycan antibodies against HIV-1 in nonhuman primates.

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Abstract

Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env-immunogen that induces a new class of neutralizing N332-glycan-independent antibodies to the conserved V3-glycan epitope of Env after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human N332-glycan-dependent (Type-I) V3-glycan bNAbs but also of a first-of-its-class N332-glycan-independent (Type-II) V3-glycan bNAb. A single immunization elicits neutralizing serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. EMPEM analysis of serum antibodies, antibody cloning and cryo-EM analysis reveal that WIN332 elicits N332-glycan-independent antibodies with remarkable sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.

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Relano-Rodriguez, I., Du, J., Lin, Z. J., Kerwin, M., Tarquis-Medina, M., Urbano, E., Cui, J., Watkins, M., Zhao, P., Habib, R., Gosh, S., Park, J., Boroughs, C., Walsh, A. A., Melo, M. B., Shaw, G. M., Hahn, B. H., Irvine, D. J., Wells, L., Weiner, D. B., Kulp, D. W., Veazey, R. S., Pallesen, J., Escolano, A.. 2025-09-09. Rapid elicitation of a new class of neutralizing N332-glycan independent V3-glycan antibodies against HIV-1 in nonhuman primates.. https://doi.org/10.1101/2025.09.04.674340

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