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-particle23.0 Å
Deposition: 22/12/2023
Map released: 29/05/2024
Last modified: 29/05/2024
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
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.
Xie Z ,
Lin YC ,
Steichen JM ,
Ozorowski G ,
Kratochvil S ,
Ray R ,
Torres JL ,
Liguori A ,
Kalyuzhniy O ,
Wang X ,
Warner JE,
Weldon SR ,
Dale GA ,
Kirsch KH,
Nair U ,
Baboo S ,
Georgeson E ,
Adachi Y ,
Kubitz M,
Jackson AM ,
Richey ST,
Volk RM,
Lee JH ,
Diedrich JK ,
Prum T ,
Falcone S,
Himansu S ,
Carfi A,
Yates 3rd JR ,
Paulson JC ,
Sok D ,
Ward AB ,
Schief WR ,
Batista FD
(2024) Science , 384 , eadk0582 - eadk0582
(2024) Science , 384 , eadk0582 - eadk0582
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.
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.