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 DOI | 10.2210/pdb8f9g/pdb |
EMDB information | 28942 28945 |
Descriptor | BG505_MD64_N332-GT5 gp120, BG505_MD64_N332-GT5 gp41, V3-glycan epitope polyclonal Fab heavy chain, ... (7 entities in total) |
Functional Keywords | mouse antibody, germline targeting, hiv-1, vaccine design, polyclonal, viral protein-immune system complex, viral protein/immune system |
Biological source | synthetic construct More |
Total number of polymer chains | 8 |
Total formula weight | 251356.59 |
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 citation | Xie, 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: 38753770DOI: 10.1126/science.adk0582 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
Download full validation report