Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and VAX004 Vaccine Trials—Balasubramanian 2018

HIV/AIDS vaccinationVAX gp120 vaccinations failed in phase III VAX003 and VAX004 trials. We investigated the kinetics of antibody (Ab) responses to the V1V2 and V3 regions of gp120 and the induction of Ab-mediated antiviral activities during 7 immunizations over 30.5 months to understand these vaccines' inadequacies. ELISA-binding Abs, viral neutralization, ADCP, and ADCC were evaluated in plasma from VAX003 and VAX004 vaccinees and placebo recipients. V1V2 and V3 Ab responses peaked after 3–4 vaccinations and dropped after 5–7. The V1V2 β-barrel underside and V3 crown epitopes showed the most deterioration. After 3 or 4 immunizations, vaccinees neutralized SF162 pseudovirus sensitive to anti-V1V2 and anti-V3 Abs better than after 7. Early and mid-time points had higher ADCP and ADCC than the end time point. Thus, VAX003 and VAX004 vaccinees produced V1V2- and V3-binding Abs and functional Abs after 3 to 4 vaccinations but not after boosts.

Balasubramanian, P., Williams, C., Shapiro, M. B., Sinangil, F., Higgins, K., Nádas, A., Totrov, M., Kong, X. P., Fiore-Gartland, A. J., Haigwood, N. L., Zolla-Pazner, S., & Hioe, C. E. (2018). Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and VAX004 Vaccine Trials. Scientific reports, 8(1), 542. https://doi.org/10.1038/s41598-017-18863-0