Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults.
BACKGROUND
The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.


RESULTS
The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).


CONCLUSIONS
This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.


BACKGROUND
Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
Hu
Jinhong
J
Changhai Hospital, Second Military Medical University, Shanghai, China.
Chen
Zhihui
Z
Gu
Jun
J
Wan
Mobin
M
Shen
Qian
Q
Kieny
Marie-Paule
MP
He
Jia
J
Li
Zhen
Z
Zhang
Qingfeng
Q
Reed
Zarifah Hussain
ZH
Zhu
Yongmei
Y
Li
Wenjie
W
Cao
Yang
Y
Qu
Li
L
Cao
Zhifang
Z
Wang
Qiang
Q
Liu
Haitao
H
Pan
Xuegong
X
Huang
Xiudong
X
Zhang
Dongmei
D
Xue
Xiangyang
X
Pan
Weiqing
W
D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry*; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000737:chemistry* / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008565:Membrane Proteins / Q000737:chemistry*; D020066:Merozoite Surface Protein 1 / Q000737:chemistry*; D008875:Middle Aged; D009829:Oleic Acids / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000378:metabolism*; D021122:Protein Subunits / Q000737:chemistry*; D015800:Protozoan Proteins / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012449:Safety
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D009829:Oleic Acids; D021122:Protein Subunits; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C090077:apical membrane antigen I, Plasmodium; C001681:mannide monooleate; D008353:Mannitol