CD4+ T cells are dispensable for induction of heterologous tier 2 HIV neutralizing antibodies in rhesus macaques

Abstract

Abstract Induction of a sustained and broad neutralizing antibody (Ab) response is a major goal in developing a protective HIV vaccine. Many HIV Envelope (Env)-specific broadly neutralizing antibodies isolated to date exhibit substantial somatic hypermutation, and their development in HIV infected individuals has been correlated with T follicular helper responses. This has bolstered the rational that a robust CD4+ T helper cell response will likely be required for the induction of such HIV broadly neutralizing antibody responses by vaccination. Using the VC10014 DNA-protein co-immunization vaccine platform consisting of gp160 envelope plasmids and gp140 trimeric envelope proteins derived from a clade B HIV-1 infected subject who developed broadly neutralizing serum Abs, and which has been previously shown to induce Tier 2 heterologous neutralizing Abs in rabbits and rhesus macaques, we determined the influence of CD4+ T cell depletion during the vaccination regimen on the characteristics of the Env-specific humoral response in rhesus macaques. Both CD4+ depleted and non-depleted animals developed Tier 2 heterologous neutralizing plasma antibodies, with no inferiority in titers among the CD4+ T cell depleted animals. Similarly, there was no diminishment of titers of HIV Env-specific cross-clade binding antibodies, antibody dependent cellular phagocytosis or antibody dependent complement deposition in the CD4+ depleted animals. These results suggest that HIV neutralizing antibodies can be induced in the absence of robust CD4+ T cell help, which may have implications for developing effective HIV vaccine strategies.