8VFV

HIV Env BG505_MD39_B16 SOSIP boosting trimer in complex with B16_d77.5 mouse Fab and RM20A3 Fab

This is a non-PDB format compatible entry.

Summary for 8VFV

• Entry DOI: 10.2210/pdb8vfv/pdb
• EMDB information: 43190
• Descriptor: RM20A3 Fab heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, RM20A3 Fab light chain, ... (10 entities in total)
• Functional Keywords: mouse antibody, germline targeting, hiv-1, vaccine design, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 14
• Total formula weight: 335814.31

Authors

Ozorowski, G.,Torres, J.L.,Ward, A.B. (deposition date: 2023-12-22, 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

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

Experimental method

ELECTRON MICROSCOPY (3.3 Å)