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.
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.


METHODS
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.


BACKGROUND
NCT01883609.
The Jenner Institute.
Tommy
T
Rampling
The Jenner Institute.
Katie J
KJ
Ewer
The Jenner Institute.
Georgina
G
Bowyer
The Jenner Institute.
Carly M
CM
Bliss
The Jenner Institute.
Nick J
NJ
Edwards
The Jenner Institute.
Danny
D
Wright
The Jenner Institute.
Ruth O
RO
Payne
The Jenner Institute.
Navin
N
Venkatraman
Royal College of Surgeons in Ireland, Dublin.
Eoghan
E
de Barra
The Jenner Institute.
Claudia M
CM
Snudden
The Jenner Institute.
Ian D
ID
Poulton
NIHR Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, United Kingdom.
Hans
H
de Graaf
NIHR Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, United Kingdom.
Priya
P
Sukhtankar
The Jenner Institute.
Rachel
R
Roberts
PATH Malaria Vaccine Initiative, Seattle, Washington.
Karen
K
Ivinson
PATH Malaria Vaccine Initiative, Seattle, Washington.
Rich
R
Weltzin
PATH Malaria Vaccine Initiative, Seattle, Washington.
Bebi-Yassin
BY
Rajkumar
PATH Malaria Vaccine Initiative, Seattle, Washington.
Ulrike
U
Wille-Reece
PATH Malaria Vaccine Initiative, Seattle, Washington.
Cynthia K
CK
Lee
PATH Malaria Vaccine Initiative, Seattle, Washington.
Christian F
CF
Ockenhouse
Department of Life Sciences.
Robert E
RE
Sinden
Centre for Statistics in Medicine, University of Oxford.
Stephen
S
Gerry
The Jenner Institute.
Alison M
AM
Lawrie
GSK Vaccines, Rixensart, Belgium.
Johan
J
Vekemans
GSK Vaccines, Rixensart, Belgium.
Danielle
D
Morelle
GSK Vaccines, Rixensart, Belgium.
Marc
M
Lievens
GSK Vaccines, Rixensart, Belgium.
Ripley W
RW
Ballou
Infectious Diseases Section, Faculty of Medicine, Department of Medicine, Imperial College London.
Graham S
GS
Cooke
NIHR Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, United Kingdom.
Saul N
SN
Faust
The Jenner Institute.
Sarah
S
Gilbert
The Jenner Institute.
Adrian V S
AV
Hill
D000256:Adenoviridae / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D004337:Drug Carriers; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007115:Immunization Schedule; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016896:Treatment Outcome; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D055815:Young Adult
D004337:Drug Carriers; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C526041:RTS,S-AS01B vaccine; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic; C069428:thrombospondin-related adhesive protein, protozoan
ChAd63; ME-TRAP; P. falciparum; RTS,S; malaria; vaccine