Greater avidity and phagocytic activity of HIV gp41-specific serum IgA antibodies in elite controllers compared to subjects on antiretroviral therapy (VIR1P.1144)

Abstract

Abstract Identification of the mechanisms of natural control of HIV replication in elite controllers (EC) may inform approaches for prevention of HIV. We investigated whether EC produce envelope-specific serum IgA responses of greater magnitude, avidity and function compared to subjects on combination antiretroviral therapy (cART). Serum was obtained from age- and race-matched HIV-uninfected women and infected women classified as EC or cART controllers (HC) or noncontrollers (HN). The EC and HC had undetectable viremia and CD4 T cell counts > 450/µl. The HN had high viremia and CD4 T cells < 250/µl. Concentrations and avidity of IgA and IgG against Clade B consensus gp120 and gp41BAL proteins were determined using ELISA. THP-1 monocytes and fluorescent beads coated with gp120 or gp41 were used to evaluate phagocytosis in whole serum and in IgA- or IgG-depleted serum. The magnitude of IgA and IgG responses to gp120 and gp41 was not found to differ between groups. Also, no differences were observed for avidity and phagocytic activity of gp120-specific antibodies. However, avidity and phagocytic activity of the anti-gp41 IgA in EC was significantly greater (p = 0.0186 or p = 0.0054 compared to HC or HN; p = 0.0474 compared to HC, respectively). These data indicate that, in EC, affinity maturation of IgA antibodies to gp41 may occur to a greater extent, resulting in gp41-specific IgA with greater antiviral function. Induction of gp41-specific IgA should be considered in vaccine design.