HIV-1 specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galcer Blocking and Phagocytosis

Wills S, et al., pii: JVI.01552-17, J Virol., 2018

Immunoglobulin A (IgA) is known to play a key role in the host defense against pathogens. However, more studies are needed to fully understand specifically the role of vaccine-elicited IgA and how they mediate antiviral functions. Described herein is the identification of antiviral functions of two HIV-1 Env-specific IgA mAbs, HG129 and HG130 obtained from peripheral blood memory B cells of a RV144 vaccinee. The HIV-1 Env 1086 C gp140 binding to HG129 and HG129 IgA binding to V3 peptide sequences were studied by using Bio-Layer Interferometry (BLI). BLI experiments were performed using two Pall ForteBio Octet instruments, OctetRED 384 and OctetRED96 equipped with Streptavidin Biosensor probes. The binding of HIV-1 Env 1086 C gp140 to HG129 was studied by immobilizing HG129 IgA antibody onto biotin-peptide M coated Streptavidin sensor tips and dipping them in various concentrations of 1086 C gp140 samples. Binding data obtained were globally fitted to a 1:1 binding model. Kinetic rate constants (kon and koff) and the equilibrium dissociation constant values (KD values) were determined. The HG129 IgA-V3 peptide binding interaction was studied by immobilizing biotin tagged V3 peptide sequences onto Streptavidin sensor tips and dipping them in wells containing different concentrations of HG129 samples. The equilibrium dissociation constant (KD) was determined using steady state analysis. Overall results of this investigation demonstrate that the two HIV-1 Env-specific IgA mAbs, HG129 and HG130 mediate monocyte phagocytosis and block HIV-1 Env glycoprotein binding to Galcer.

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