A phase 1b randomized, controlled, double-blinded dosage-escalation trial to evaluate the safety, reactogenicity and immunogenicity of an adenovirus type 35 based circumsporozoite malaria vaccine in Burkinabe healthy adults 18 to 45 years of age.
BACKGROUND
Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.


METHODS
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 10(9), 10(10), 5X10(10), 10(11) vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.


RESULTS
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.


CONCLUSIONS
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.


BACKGROUND
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459.
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
Alphonse
A
Ouédraogo
Alfred B
AB
Tiono
Désiré
D
Kargougou
Jean Baptiste
JB
Yaro
Esperance
E
Ouédraogo
Youssouf
Y
Kaboré
David
D
Kangoye
Edith C
EC
Bougouma
Adama
A
Gansane
Noelie
N
Henri
Amidou
A
Diarra
Souleymane
S
Sanon
Issiaka
I
Soulama
Amadou T
AT
Konate
Nora L
NL
Watson
Valerie
V
Brown
Jenny
J
Hendriks
Maria Grazia
MG
Pau
Isabella
I
Versteege
Edison
E
Wiesken
Jerald
J
Sadoff
Issa
I
Nebie
Sodiomon B
SB
Sirima
D000256:Adenoviridae; D000293:Adolescent; D000328:Adult; D002050:Burkina Faso; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan