Identification of correlates of HIV-1 Neutralizing Antibodies through a systems serology approach 2307607

Abstract Introduction 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. Funding Source National Institute of Health, UM1AI164566 Topic Categories Vaccines and Immunotherapy (VAC)