8F9M

HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized wild type mice, and NHP monoclonal Fab RM20A3

これはPDB形式変換不可エントリーです。

8F9M の概要

• エントリーDOI: 10.2210/pdb8f9m/pdb
• EMDBエントリー: 28942 28945
• 分子名称: BG505_MD64_N332-GT5 gp120, RM20A3 Fab Heavy Chain, RM20A3 Fab Light Chain, ... (9 entities in total)
• 機能のキーワード: mouse antibody, germline targeting, hiv-1, vaccine design, polyclonal, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 331295.09

構造登録者

Ozorowski, G.,Ward, A.B. (登録日: 2022-11-23, 公開日: 2024-05-15, 最終更新日: 2024-05-29)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.1 Å)