MassIVE MSV000094176

Partial Public PXD050174

mRNA-LNP HIV-1 trimer boosters elicit precursors to bnAbs

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Description

Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized Ig knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18, and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off target V1-binding responses. The delivery of the prime and boost immunogens as mRNA-LNPs generated long-lasting GCs, somatic hypermutation, and affinity maturation, and may, therefore, be an effective tool in HIV vaccine development. [doi:10.25345/C5NV99N53] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: DeGlyPHER ; N-glycans ; HIV Env Trimer ; mRNA vaccine ; V3-glycan epitope ; bNAb ; germline targeting

Contact

Principal Investigators:
(in alphabetical order) 		John R. Yates III, The Scripps Research Institute, USA
Submitting User: sbaboo
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