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.
- MeSH
- epitopy MeSH
- genové produkty env - virus lidské imunodeficience MeSH
- HIV infekce * MeSH
- HIV protilátky MeSH
- HIV-1 * MeSH
- imunoglobulin A MeSH
- imunoglobulin G MeSH
- lidé MeSH
- myši MeSH
- neutralizující protilátky MeSH
- non-progresoři MeSH
- polysacharidy MeSH
- široce neutralizující protilátky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- černoši nebo Afroameričané * MeSH
- imunosupresivní léčba MeSH
- kvalita života MeSH
- lidé MeSH
- pigmentace kůže * MeSH
- rejekce štěpu diagnóza MeSH
- senioři MeSH
- transplantace obličeje * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
- Research Support, N.I.H., Extramural MeSH
- Publikační typ
- abstrakt z konference MeSH
