JCI Insight (May 2023)

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

  • 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

Journal volume & issue
Vol. 8, no. 9

Abstract

Read online

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.

Keywords