Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide
Name
fimmu-15-1484029.pdf
Description
Published version
Size
9.54 MB
Format
Adobe PDF
Checksum (MD5)
9569c617d0b9d66e997c788385299d3e
Author(s)
Reveiz, Mateo
Xu, Kai
Lee, Myungjin
Wang, Shuishu
Olia, Adam S
Harris, Darcy R
Liu, Kevin
Liu, Tracy
Schaub, Andrew J
Stephens, Tyler
Date Issued
November 14, 2024
Journal
Frontiers in Immunology
Publisher
Frontiers Media SA
Citation
Reveiz M, Xu K, Lee M, Wang S, Olia AS, Harris DR, Liu K, Liu T, Schaub AJ, Stephens T, Wang Y, Zhang B, Huang R, Tsybovsky Y, Kwong PD and Rawi R (2024) Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide. Front. Immunol. 15:1484029.
Version
Final published version
Abstract
Broadly neutralizing antibodies have been proposed as templates for HIV-1 vaccine design, but it has been unclear how similar vaccine-elicited antibodies are to their naturally elicited templates. To provide insight, here we compare the recognition of naturally elicited and vaccine-elicited antibodies targeting the HIV-1 fusion peptide, which comprises envelope (Env) residues 512–526, with the most common sequence being AVGIGAVFLGFLGAA. Naturally elicited antibodies bound peptides with substitutions to negatively charged amino acids at residue positions 517–520 substantially better than the most common sequence, despite these substitutions rarely appearing in HIV-1; by contrast, vaccine-elicited antibodies were less tolerant of sequence variation, with no substitution of residues 512–516 showing increased binding. Molecular dynamics analysis and cryo-EM structural analysis of the naturally elicited ACS202 antibody in complex with the HIV-1 Env trimer with an alanine 517 to glutamine substitution suggested enhanced binding to result from electrostatic interactions with positively charged antibody residues. Overall, vaccine-elicited antibodies appeared to be more fully optimized to bind the most common fusion peptide sequence, perhaps reflecting the immunization with fusion peptide of the vaccine-elicited antibodies.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3389/fimmu.2024.1484029
