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

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.

Author information

1
The Jenner Institute.
2
Royal College of Surgeons in Ireland, Dublin.
3
NIHR Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, United Kingdom.
4
PATH Malaria Vaccine Initiative, Seattle, Washington.
5
Department of Life Sciences.
6
Centre for Statistics in Medicine, University of Oxford.
7
GSK Vaccines, Rixensart, Belgium.
8
Infectious Diseases Section, Faculty of Medicine, Department of Medicine, Imperial College London.

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

PMID:
27307573
PMCID:
PMC4978377
DOI:
10.1093/infdis/jiw244
[Indexed for MEDLINE]
Free PMC Article

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