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Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Abstract : Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.
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Submitted on : Thursday, April 28, 2022 - 2:44:44 PM
Last modification on : Thursday, May 5, 2022 - 4:15:53 PM

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Valerie Lorin, Ignacio Fernández, Guillemette Masse-Ranson, Mélanie Bouvin-Pley, Luis M. Molinos-Albert, et al.. Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller. Journal of Experimental Medicine, Rockefeller University Press, 2022, 219 (3), pp.e20212045. ⟨10.1084/jem.20212045⟩. ⟨pasteur-03654254⟩

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