P04-48. HIV-1 envelope induces memory B cell responses that correlate with plasma antibody levels after gp120 protein vaccination or chronic HIV-1 infection

Background

Successful vaccines (e.g. tetanus) can induce long-lived antibody levels that are maintained by long-lived plasma cells and do not correlate with numbers of blood memory B-cells. Early events during HIV-1 acute infection may impair the timely onset of neutralizing antibody responses. Thus, an effective HIV-1 vaccine should elicit high levels of durable antibodies by long-lived plasma cells. We asked if HIV-1 envelope-specific memory responses are sustained by memory B-cells in the settings of HIV-1 gp120 envelope vaccination and chronic HIV-1 infection (CHI).

Methods

Total, gp140 envelope and V3-specific IgG memory B-cells from PBMCs of 26 CHI patients and 25 vaccinated volunteers from the VaxGen clinical trial VAX004 were enumerated with ELISpot assays after in vitro stimulation. Respective plasma antibody levels were tested with ELISA. An additional 8 CHI subjects, treated with ART for between 125 and 387 weeks and with viremia suppression, were studied for levels of anti-gp120, -gp41, -p55, -tetanus toxoid and -influenza IgG plasma antibodies (Luminex assay and ELISA) over time of ART to determine the relative antibody level half-lives.

Results

Levels of anti-HIV-1 envelope plasma antibodies and memory B-cells correlated both in CHI and vaccinated individuals. Moreover, whereas the reported expected half-life of plasma antibody levels to protein vaccines is >10 years when maintained by long-lived plasma cells (we observed ~11 years for tetanus), plasma anti-envelope antibody level half-lives were ~33–81 weeks in ART-induced aviremic CHI subjects. In contrast, anti-p55 Gag antibody level half-life was 648 weeks and antibody titers against influenza did not decay in-between yearly or biennial influenza vaccine boosts.

Conclusion

These data demonstrated that HIV-1 envelope induces predominantly short-lived memory B-cell-dependent plasma antibodies in the settings of envelope vaccination and chronic HIV-1 infection. The inability to generate high titers of long-lived anti-envelope antibodies is a major hurdle to overcome for the development of a successful HIV-1 vaccine.