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8F9G

HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized BG18HCgl knock-in mice

This is a non-PDB format compatible entry.
Summary for 8F9G
Entry DOI10.2210/pdb8f9g/pdb
EMDB information28942 28945
DescriptorBG505_MD64_N332-GT5 gp120, BG505_MD64_N332-GT5 gp41, V3-glycan epitope polyclonal Fab heavy chain, ... (7 entities in total)
Functional Keywordsmouse antibody, germline targeting, hiv-1, vaccine design, polyclonal, viral protein-immune system complex, viral protein/immune system
Biological sourcesynthetic construct
More
Total number of polymer chains8
Total formula weight251356.59
Authors
Ozorowski, G.,Torres, J.L.,Ward, A.B. (deposition date: 2022-11-23, release date: 2024-05-15, Last modification date: 2024-11-13)
Primary citationXie, Z.,Lin, Y.C.,Steichen, J.M.,Ozorowski, G.,Kratochvil, S.,Ray, R.,Torres, J.L.,Liguori, A.,Kalyuzhniy, O.,Wang, X.,Warner, J.E.,Weldon, S.R.,Dale, G.A.,Kirsch, K.H.,Nair, U.,Baboo, S.,Georgeson, E.,Adachi, Y.,Kubitz, M.,Jackson, A.M.,Richey, S.T.,Volk, R.M.,Lee, J.H.,Diedrich, J.K.,Prum, T.,Falcone, S.,Himansu, S.,Carfi, A.,Yates 3rd, J.R.,Paulson, J.C.,Sok, D.,Ward, A.B.,Schief, W.R.,Batista, F.D.
mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies.
Science, 384:eadk0582-eadk0582, 2024
Cited by
PubMed 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.
PubMed: 38753770
DOI: 10.1126/science.adk0582
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.2 Å)
Structure validation

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