Epitopes for neutralizing antibodies induced by HIV-1 envelope glycoprotein BG505 SOSIP trimers in rabbits and macaques

PLoS Pathogens
P J KlasseJohn P Moore

Abstract

The native-like, soluble SOSIP.664 trimer based on the BG505 clade A env gene of HIV-1 is immunogenic in various animal species, of which the most studied are rabbits and rhesus macaques. The trimer induces autologous neutralizing antibodies (NAbs) consistently but at a wide range of titers and with incompletely determined specificities. A precise delineation of immunogenic neutralization epitopes on native-like trimers could help strategies to extend the NAb response to heterologous HIV-1 strains. One autologous NAb epitope on the BG505 Env trimer is known to involve residues lining a hole in the glycan shield that is blocked by adding a glycan at either residue 241 or 289. This glycan-hole epitope accounts for the NAb response of most trimer-immunized rabbits but not for that of a substantial subset. Here, we have used a large panel of mutant BG505 Env-pseudotyped viruses to define additional sites. A frequently immunogenic epitope in rabbits is blocked by adding a glycan at residue 465 near the junction of the gp120 V5 loop and β24 strand and is influenced by amino-acid changes in the structurally nearby C3 region. We name this new site the "C3/465 epitope". Of note is that the C3 region was under selection pressure in the i...Continue Reading

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Citations

Apr 20, 2018·International Journal of Molecular Sciences·Maria TrovatoPiergiuseppe De Berardinis
Sep 5, 2019·Vaccines·Behazine CombadièreVincent Vieillard
Sep 1, 2020·PLoS Pathogens·Christopher A CottrellMarit J van Gils
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Methods Mentioned

BETA
ELISA

Software Mentioned

Prism
Graphpad
Prism Graphpad

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