TY - JOUR
T1 - The breadth of HIV-1 neutralizing antibodies depends on the conservation of key sites in their epitopes
AU - Bai, Hongjun
AU - Li, Yifan
AU - Michael, Nelson L.
AU - Robb, Merlin L.
AU - Rolland, Morgane
N1 - Funding Information:
This work was supported by a cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of the Army [W81XWH-11-2-0174]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Drs. Ivelin Georgiev, Cinque Soto and Peter Kwong for sharing data and helpful discussion. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or the Department of Health and Human Services.
Publisher Copyright:
© 2019 Bai et al.
PY - 2019/6
Y1 - 2019/6
N2 - Developing HIV-1 vaccines that trigger broadly neutralizing antibodies (bnAbs) is a priority as bnAbs are considered key to elicitation of a protective immune response. To investigate whether the breadth of a neutralizing antibody (nAb) depended on the conservation of its epitope among circulating viruses, we examined Antibody:Envelope (Ab:Env) interactions and worldwide Env diversity. We found that sites corresponding to bnAb epitopes were as variable as other accessible, non-hypervariable Env sites (p = 0.50, Mann-Whitney U-test) with no significant relationship between epitope conservation and neutralization breadth (Spearman’s ρ =-0.44, adjusted p = 0.079). However, when accounting for key sites in the Ab:Env interaction, we showed that the broadest bnAbs targeted more conserved epitopes (Spearman’s ρ =-0.70, adjusted p = 5.0e-5). Neutralization breadth did not stem from the overall conservation of Ab epitopes but depended instead on the conservation of key sites of the Ab:Env interaction, revealing a mechanistic basis for neutralization breadth that could be exploited for vaccine design.
AB - Developing HIV-1 vaccines that trigger broadly neutralizing antibodies (bnAbs) is a priority as bnAbs are considered key to elicitation of a protective immune response. To investigate whether the breadth of a neutralizing antibody (nAb) depended on the conservation of its epitope among circulating viruses, we examined Antibody:Envelope (Ab:Env) interactions and worldwide Env diversity. We found that sites corresponding to bnAb epitopes were as variable as other accessible, non-hypervariable Env sites (p = 0.50, Mann-Whitney U-test) with no significant relationship between epitope conservation and neutralization breadth (Spearman’s ρ =-0.44, adjusted p = 0.079). However, when accounting for key sites in the Ab:Env interaction, we showed that the broadest bnAbs targeted more conserved epitopes (Spearman’s ρ =-0.70, adjusted p = 5.0e-5). Neutralization breadth did not stem from the overall conservation of Ab epitopes but depended instead on the conservation of key sites of the Ab:Env interaction, revealing a mechanistic basis for neutralization breadth that could be exploited for vaccine design.
UR - http://www.scopus.com/inward/record.url?scp=85068488044&partnerID=8YFLogxK
U2 - 10.1371/journal.pcbi.1007056
DO - 10.1371/journal.pcbi.1007056
M3 - Article
C2 - 31170145
AN - SCOPUS:85068488044
SN - 1553-734X
VL - 15
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 6
M1 - e1007056
ER -