Research Assistant 2 Harvard Univ. Chan Sch. of Pub. Hlth., United States
Disclosure(s):
Ross Blanc: No relevant disclosure to display
Introduction/Rationale: Antibodies utilize their antigen-binding fragment (Fab) and fragment crystallizable (Fc) domains to provide protection against infectious pathogens. Recent work has shown that the Fc region plays an as-yet fully understood role in antibody breadth coverage and neutralization potency. We sought to identify antibody features correlated to neutralization capacity at the systems level to HIV-1.
Methods: A systems-based predictive neutralizing antibody (SNAb) assay was used to quantify HIV-1 neutralization across diverse envelope glycoproteins representing multiple clades and subtypes, using specimens from HIV-vaccinated (Ad26/MVA) non-human primates (NHPs). These NHPs were further subdivided into groups receiving the monoclonal antibody (mAb) PGT121 or placebo to characterize how exogenous mAbs influence the neutralizing antibody profile.
Results: Predicted neutralizing antibodies to HIV-1 Env isolates and clades were quantified through SNAb, and showed heterogeneous neutralization capacities for all treatment arms. Correlations between antibody binding and Fc-receptor binding antibodies to the predicted neutralization titers are ongoing.
Conclusion: Our approach provides a method for dissecting correlates of HIV-1 neutralizing activity that may inform future vaccine and/or mAb therapy design. Future studies understanding how these neutralization signatures relate to latent reservoir expansion/contraction are ongoing.
