7JKS

Crystal structure of vaccine-elicited broadly neutralizing VRC01-class antibody 2411a in complex with HIV-1 gp120 core

Summary for 7JKS

• Entry DOI: 10.2210/pdb7jks/pdb
• Descriptor: HIV-1 gp120 core, The heavy chain of antibody 2411a, The light chain of antibody 2411a, ... (6 entities in total)
• Functional Keywords: broadly neutralizing antibody, vrc01-class, vaccine-elicited, hiv-1, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 93002.73

Authors

Zhou, T.,Chen, X.,Kwong, P.D.,Mascola, J.R. (deposition date: 2020-07-28, release date: 2021-06-09, Last modification date: 2024-10-30)

Primary citation

Chen, X.,Zhou, T.,Schmidt, S.D.,Duan, H.,Cheng, C.,Chuang, G.Y.,Gu, Y.,Louder, M.K.,Lin, B.C.,Shen, C.H.,Sheng, Z.,Zheng, M.X.,Doria-Rose, N.A.,Joyce, M.G.,Shapiro, L.,Tian, M.,Alt, F.W.,Kwong, P.D.,Mascola, J.R.
Vaccination induces maturation in a mouse model of diverse unmutated VRC01-class precursors to HIV-neutralizing antibodies with >50% breadth.
Immunity, 54:324-339.e8, 2021

PubMed Abstract: Vaccine elicitation of broadly neutralizing antibodies (bnAbs) is a key HIV-research goal. The VRC01 class of bnAbs targets the CD4-binding site on the HIV-envelope trimer and requires extensive somatic hypermutation (SHM) to neutralize effectively. Despite substantial progress, vaccine-induced VRC01-class antibodies starting from unmutated precursors have exhibited limited neutralization breadth, particularly against viruses bearing glycan on loop D residue N276 (glycan276), present on most circulating strains. Here, using sequential immunization of immunoglobulin (Ig)-humanized mice expressing diverse unmutated VRC01-class antibody precursors, we elicited serum responses capable of neutralizing viruses bearing glycan276 and isolated multiple lineages of VRC01-class bnAbs, including two with >50% breadth on a 208-strain panel. Crystal structures of representative bnAbs revealed the same mode of recognition as known VRC01-class bnAbs. Structure-function studies further pinpointed key mutations and correlated their induction with specific immunizations. VRC01-class bnAbs can thus be matured by sequential immunization from unmutated ancestors to >50% breadth, and we delineate immunogens and regimens inducing key SHM.

PubMed: 33453152
DOI: 10.1016/j.immuni.2020.12.014

Experimental method

X-RAY DIFFRACTION (3.45 Å)