EMD-43192

Single-particle
23.0 Å
EMD-43192 Deposition: 22/12/2023
Map released: 29/05/2024
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-43192

N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at day 15 from N332-GT5 nanoparticle-immunized BG18HCgl knock-in mice

EMD-43192

Single-particle
23.0 Å
EMD-43192 Deposition: 22/12/2023
Map released: 29/05/2024
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus
Sample: N332-GT5 SOSIP in complex with V1V3 polyclonal Fabs isolated at day 15 from N332-GT5 nanoparticle-immunized BG18HCgl knock-in mice

Deposition Authors: Ozorowski G , Torres JL , Ward AB
mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.
PUBMED: 38753770
DOI: doi:10.1126/science.adk0582
ISSN: 1095-9203
ASTM: SCIEAS
Abstract:
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 immunoglobulin 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 messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.