6U6O

Crystal structure of a vaccine-elicited anti-HIV-1 rhesus macaque antibody DH846

6U6O の概要

• エントリーDOI: 10.2210/pdb6u6o/pdb
• 分子名称: DH846 Fab heavy chain, DH846 Fab light chain (3 entities in total)
• 機能のキーワード: fab fragment, hiv, antibody, immune system, rhesus macaque, vaccine-elicited
• 由来する生物種: Macaca mulatta (Rhesus monkey); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47412.69

構造登録者

Chen, W.-H.,Choe, M.,Saunders, K.O.,Joyce, M.G. (登録日: 2019-08-30, 公開日: 2021-03-24, 最終更新日: 2024-10-09)

主引用文献

Cai, F.,Chen, W.H.,Wu, W.,Jones, J.A.,Choe, M.,Gohain, N.,Shen, X.,LaBranche, C.,Eaton, A.,Sutherland, L.,Lee, E.M.,Hernandez, G.E.,Wu, N.R.,Scearce, R.,Seaman, M.S.,Moody, M.A.,Santra, S.,Wiehe, K.,Tomaras, G.D.,Wagh, K.,Korber, B.,Bonsignori, M.,Montefiori, D.C.,Haynes, B.F.,de Val, N.,Joyce, M.G.,Saunders, K.O.
Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.
Plos Pathog., 17:e1009624-e1009624, 2021

PubMed Abstract: A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.

PubMed: 34086838
DOI: 10.1371/journal.ppat.1009624

実験手法

X-RAY DIFFRACTION (2.806 Å)