Randomized, Double-Blind Evaluation of Late Boost Strategies for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial

J Infect Dis. 2017 Apr 15;215(8):1255-1263. doi: 10.1093/infdis/jix099.

Abstract

Background: The RV144 ALVAC-HIV prime, AIDSVAX B/E boost afforded 60% efficacy against human immunodeficiency virus (HIV) acquisition at 1 year, waning to 31.2% after 3.5 years. We hypothesized that additional vaccinations might augment immune correlates of protection.

Methods: In a randomized placebo-controlled double-blind study of 162 HIV-negative RV144 vaccine recipients, we evaluated 2 additional boosts, given 6-8 years since RV144 vaccination, for safety and immunogenicity, at weeks 0 and 24. Study groups 1-3 received ALVAC-HIV+AIDSVAX B/E, AIDSVAX B/E, and ALVAC-HIV, respectively, or placebo.

Results: Vaccines were well tolerated. For groups 1 and 2, plasma immunoglobulin (Ig) G, IgA, and neutralizing antibody responses at week 2 were all significantly higher than 2 weeks after the last RV144 vaccination. IgG titers against glycoprotein (gp) 70V1V2 92TH023 increased 14-fold compared with 2 weeks after the last RV144 vaccination (14069 vs 999; P < .001). Groups 1 and 2 did not differ significantly from each other, whereas group 3 was similar to placebo recipients. Responses in groups 1 and 2 declined by week 24 but were boosted by the second vaccination, albeit at lower magnitude than for week 2.

Conclusions: In RV144 vaccinees, AIDSVAX B/E with or without ALVAC-HIV 6-8 years after initial vaccination generated higher humoral responses than after RV144, but these responses were short-lived, and their magnitude did not increase with subsequent boost.

Clinical trials registration: NCT01435135.

Keywords: HIV; RV144; prime-boost.; vaccine.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • Adult
  • Antibodies, Neutralizing / blood
  • Cytokines / immunology
  • Double-Blind Method
  • Female
  • HIV Antibodies / blood
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / prevention & control*
  • HIV-1
  • Healthy Volunteers
  • Humans
  • Immunity, Humoral*
  • Immunization, Secondary*
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Male
  • Thailand

Substances

  • AIDS Vaccines
  • AIDSVAX
  • AIDSVAX B-E
  • Antibodies, Neutralizing
  • Cytokines
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin A
  • Immunoglobulin G

Associated data

  • ClinicalTrials.gov/NCT01435135