IgG3 enhances neutralization potency and Fc effector function of the CAP256-VRC26.25 antibody

31 January 2020

In yet another interesting angle to the CAP256 story, researchers at the NICD discovered that members of the CAP256-VRC26 antibody lineage were naturally expressed as IgG3.  This antibody isotype is known to mediate the broadest range of Fc effector functions and IgG3 has been associated with HIV vaccine efficacy and HIV control.

 Simone Richardson (right in the photo), a post-doctoral fellow at the NICD engineered and expressed the CAP256-VRC26.25 broadly neutralizing antibody (bNAb) as an IgG3. She found that IgG3 variants had significantly higher phagocytosis and trogocytosis compared to the IgG1 version. Interestingly, neutralization potency was also significantly higher for IgG3 bNAbs, particularly against viruses lacking the N160 glycan.

 She was able to confirm experimentally that the long hinge region was responsible for this improved functionality probably due to the flexibility of the IgG3 molecule.

 These data suggest that isotype may be tuned to enhance both neutralization and cytotoxic activity of bNAbs that could improve the efficacy of passive immunization strategies for HIV prevention. This study was published in PLoS Pathogens in December 2019 and Simone is now exploring whether IgG3 can be used to improve the functionality of other bNAbs.