8G4T

Vaccine-elicited human antibody 2C09 in complex with HIV-1 envelope trimer BG505 DS-SOSIP

Summary for 8G4T

• Entry DOI: 10.2210/pdb8g4t/pdb
• EMDB information: 29731
• Descriptor: Envelope glycoprotein BG505 DS-SOSIP gp41, Envelope glycoprotein BG505 DS-SOSIP gp120, Fab 2C09 heavy chain, ... (9 entities in total)
• Functional Keywords: antibody-antigen complex vaccine-elicited antibody fusion peptide strain specific, antiviral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 380886.60

Authors

Wang, S.,Kwong, P.D. (deposition date: 2023-02-10, release date: 2023-07-12, Last modification date: 2024-10-30)

Primary citation

Wang, S.,Matassoli, F.,Zhang, B.,Liu, T.,Shen, C.H.,Bylund, T.,Johnston, T.,Henry, A.R.,Teng, I.T.,Tripathi, P.,Becker, J.E.,Changela, A.,Chaudhary, R.,Cheng, C.,Gaudinski, M.,Gorman, J.,Harris, D.R.,Lee, M.,Morano, N.C.,Novik, L.,O'Dell, S.,Olia, A.S.,Parchment, D.K.,Rawi, R.,Roberts-Torres, J.,Stephens, T.,Tsybovsky, Y.,Wang, D.,Van Wazer, D.J.,Zhou, T.,Doria-Rose, N.A.,Koup, R.A.,Shapiro, L.,Douek, D.C.,McDermott, A.B.,Kwong, P.D.
HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.
Cell Rep, 42:112755-112755, 2023

PubMed Abstract: Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.

PubMed: 37436899
DOI: 10.1016/j.celrep.2023.112755

Experimental method

ELECTRON MICROSCOPY (2.81 Å)