Enhanced neutralization potency of an identical HIV neutralizing antibody expressed as different isotypes is achieved through genetically distinct mechanisms.

Antibodies with the same variable region can exist as multiple isotypes with varying neutralization potencies, though the mechanism for this is not fully defined. We previously isolated an HIV-directed IgA1 monoclonal antibody (mAb), CAP88-CH06, and showed that IgA1 and IgG3 isotypes of this antibody demonstrated enhanced neutralization compared to IgG1. To explore the mechanism behind this, hinge region and constant heavy chain (CH1) chimeras were constructed between the IgA1, IgG3 and IgG1 mAbs and assessed for neutralization activity, antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC).

T cell responses to SARS-CoV-2 spike cross-recognize Omicron.

The SARS-CoV-2 Omicron variant (B.1.1.

Rapid and Focused Maturation of a VRC01-Class HIV Broadly Neutralizing Antibody Lineage Involves Both Binding and Accommodation of the N276-Glycan.

The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063.

HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual.

Unlabelled: The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs).