Safety and Immunogenicity of an AS03 B-Adjuvanted Inactivated Tetravalent Dengue Virus Vaccine Administered on Varying Schedules to Healthy U.S. Adults: A Phase 1/2 Randomized Study

Am J Trop Med Hyg. 2020 Jul;103(1):132-141. doi: 10.4269/ajtmh.19-0738. Epub 2020 Apr 23.

Abstract

Dengue disease and its causative agents, the dengue viruses (DENV-1-4), cause high morbidity in tropical and subtropical regions. We evaluated three dosing regimens of the investigational tetravalent AS03B-adjuvanted dengue-purified inactivated vaccine (DPIV+AS03B). In this phase 1/2, observer-blind, placebo-controlled study (NCT02421367), 140 healthy adults were randomized 1:1:2 to receive DPIV+AS03B according to the following regimens: 0-1 month (M), 0-1-6 M, or 0-3 M. Participants received DPIV+AS03B or placebo at M0, M1, M3, and M6 according to their dosing schedule. Primary objectives were 1) to evaluate the safety of DPIV+AS03B for 28 days (D) after each dose; 2) to demonstrate the added value of a booster dose (0-1-6 M versus 0-1 M) based on neutralizing antibody titers to each DENV type (DENV-1-4) at 28 D after the last dose; and, if this objective was met, 3) to demonstrate the benefit of a longer interval between the first and second doses (0-1 M versus 0-3 M). Adverse events (AEs) within 7 D after vaccination tended to be more frequent after DPIV+AS03B doses than placebo; the number of grade 3 AEs was low (≤ 4.5% after DPIV+AS03B; ≤ 2.9% after placebo), with no obvious differences across groups. Within 28 D following each dose, the frequency of unsolicited AEs after DPIV+AS03B appeared higher for three-dose (0-1-6 M) than two-dose (0-1 M and 0-3 M) regimens. No serious AEs were considered related to vaccination, and no potential immune-mediated diseases were reported during the study. All three schedules were well tolerated. Both primary immunogenicity objectives were demonstrated. The 0-3 M and 0-1-6 M regimens were more immunogenic than the 0-1 M regimen.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Viral / biosynthesis*
  • Dengue / immunology
  • Dengue / prevention & control*
  • Dengue / virology
  • Dengue Vaccines / administration & dosage*
  • Dengue Vaccines / adverse effects
  • Dengue Vaccines / biosynthesis
  • Dengue Virus / immunology*
  • Female
  • Healthy Volunteers
  • Humans
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • Patient Safety
  • Vaccination / methods*
  • Vaccines, Attenuated
  • Vaccines, Subunit

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated
  • Vaccines, Subunit

Associated data

  • ClinicalTrials.gov/NCT02421367