Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP

J Infect Dis. 2016 Sep 1;214(5):772-81. doi: 10.1093/infdis/jiw244. Epub 2016 Jun 15.

Abstract

Background: The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector.

Method: Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls.

Results: No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected.

Conclusions: The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.

Clinical trials registration: NCT01883609.

Keywords: ChAd63; ME-TRAP; P. falciparum; RTS,S; malaria; vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adenoviridae / genetics
  • Adolescent
  • Adult
  • Animals
  • Drug Carriers*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Healthy Volunteers
  • Humans
  • Immunization Schedule*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / adverse effects*
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Protozoan Proteins / administration & dosage
  • Protozoan Proteins / immunology*
  • Treatment Outcome
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Vaccinia virus / genetics
  • Young Adult

Substances

  • Drug Carriers
  • Malaria Vaccines
  • Protozoan Proteins
  • RTS,S-AS01B vaccine
  • Vaccines, Combined
  • Vaccines, Synthetic
  • thrombospondin-related adhesive protein, protozoan

Associated data

  • ClinicalTrials.gov/NCT01883609