EMD-8977
Cryo-EM structure at 3.2 A resolution of HIV-1 fusion peptide-directed antibody, A12V163-b.01, elicited by vaccination of Rhesus macaques, in complex with stabilized HIV-1 Env BG505 DS-SOSIP, which was also bound to antibodies VRC03 and PGT122
EMD-8977
Single-particle3.18 Å
![EMD-8977](/em_static/emdb/emdb_no_image.png)
Map released: 11/09/2019
Last modified: 11/09/2019
Sample Organism:
Homo sapiens,
Human immunodeficiency virus 1,
Macaca mulatta
Sample: Quaternary complex of HIV-1 Env BG505 DS-SOSIP with antibodies A12V163-b.01, VRC03 and PGT122.
Deposition Authors: Acharya P, Eng ET, Kwong PD
Sample: Quaternary complex of HIV-1 Env BG505 DS-SOSIP with antibodies A12V163-b.01, VRC03 and PGT122.
Deposition Authors: Acharya P, Eng ET, Kwong PD
Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
Kong R,
Duan H
,
Sheng Z,
Xu K,
Acharya P
,
Chen X,
Cheng C,
Dingens AS,
Gorman J
,
Sastry M,
Shen CH,
Zhang B,
Zhou T,
Chuang GY,
Chao CW,
Gu Y,
Jafari AJ,
Louder MK,
O'Dell S,
Rowshan AP,
Viox EG,
Wang Y,
Choi CW,
Corcoran MM
,
Corrigan AR
,
Dandey VP,
Eng ET
,
Geng H,
Foulds KE,
Guo Y
,
Kwon YD,
Lin B,
Liu K,
Mason RD,
Nason MC,
Ohr TY,
Ou L,
Rawi R,
Sarfo EK
,
Schon A,
Todd JP,
Wang S,
Wei H,
Wu W,
Mullikin JC,
Bailer RT,
Doria-Rose NA,
Karlsson Hedestam GB,
Scorpio DG,
Overbaugh J,
Bloom JD,
Carragher B,
Potter CS,
Shapiro L,
Kwong PD,
Mascola JR
(2019) Cell , 178 , 567 - 584.e19
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(2019) Cell , 178 , 567 - 584.e19
Abstract:
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.