title: Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults.
abstract: 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].
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Hu
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Mobin
authors.initials: M
authors.lastname: Wan
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Kieny
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zarifah Hussain
authors.initials: ZH
authors.lastname: Reed
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Qu
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Cao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Liu
authors.forename: Xuegong
authors.initials: X
authors.lastname: Pan
authors.forename: Xiudong
authors.initials: X
authors.lastname: Huang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xue
authors.forename: Weiqing
authors.initials: W
authors.lastname: Pan
mesh_terms: 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
chemical_list: 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