EMD-28942
HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized BG18HCgl knock-in mice
EMD-28942
Single-particle3.2 Å

Map released: 15/05/2024
Last modified: 13/11/2024
Sample Organism:
Mus musculus,
synthetic construct
Sample: HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized BG18HCgl knock-in mice V3-glycan epitope polyclonal Fab heavy chain
Fitted models: 8f9g (Avg. Q-score: 0.446)
Deposition Authors: Ozorowski G
,
Torres JL
,
Ward AB
Sample: HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized BG18HCgl knock-in mice V3-glycan epitope polyclonal Fab heavy chain
Fitted models: 8f9g (Avg. Q-score: 0.446)
Deposition Authors: Ozorowski G



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.