Abstract
The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.
Authors
Margaret C. Costanzo, Dominic Paquin-Proulx, Alexandra Schuetz, Siriwat Akapirat, Zhanna Shubin, Dohoon Kim, Lindsay Wieczorek, Victoria R. Polonis, Hung V. Trinh, Mangala Rao, Hanna Anenia, Michael D. Barrera, Jacob Boeckelman, Barbara Nails, Pallavi Thapa, Michelle Zemil, Carlo Sacdalan, Eugene Kroon, Boot Kaewboon, Somporn Tipsuk, Surat Jongrakthaitae, Sanjay Gurunathan, Faruk Sinangil, Jerome H. Kim, Merlin L. Robb, Julie A. Ake, Robert J. O’Connell, Punnee Pitisutthithum, Sorachai Nitayaphan, Suwat Chariyalertsak, Michael A. Eller, Nittaya Phanuphak, Sandhya Vasan, the RV306, RV328 study groups
Figure 4
TZM-bl neutralizing antibody levels and antibody effector function levels after 3 AIDSVAX B/E vaccinations in participants who received ALVAC-HIV versus participants who received AIDSVAX B/E alone.
