HIV-specific Fc effector function early in infection predicts broadly neutralizing antibody development

3 May 2018

A study by Simone Richardson (right), a PhD student at the National Institutes for Communicable Diseases (NICD) was recently published in PLoS Pathogens entitled “HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies”.  Simone is supervised by Professor Lynn Morris, CAPRISA Research Associate and Dr Nono Mkhize, a senior scientist at NICD.

   While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. This study showed that HIV-infected individuals from the CAPRISA cohort who show a diversified and potent Fc response early in infection were more likely to develop bNAbs later on. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens, which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. This provides evidence for a common mechanistic link between the regulation of the Fc and Fab mediated activities in these

“Simone has done ground-breaking work. She is one of the few people who has examined both ends of the antibody molecule. Most people study one end or the other!” said Prof Morris. “Her finding that an Fc effector function profile that arises early and predicts neutralization breadth could have important implications for the testing of vaccine candidates designed to generate neutralizing antibodies”, she added.  

For further reading see:

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006987

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Figure: Early Fc effector function can predict the development of broadly neutralizing antibodies