PMID- 18398475
OWN - NLM
STAT- MEDLINE
DCOM- 20080610
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 4
DP  - 2008 Apr 9
TI  - Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 
      chimeric protein formulated in montanide ISA 720 in healthy adults.
PG  - e1952
LID - 10.1371/journal.pone.0001952 [doi]
LID - e1952
AB  - 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. 
      METHODS AND FINDINGS: 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). CONCLUSION: 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. TRIAL REGISTRATION: Chinese State Food and Drug Administration 
      (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
FAU - Hu, Jinhong
AU  - Hu J
AD  - Changhai Hospital, Second Military Medical University, Shanghai, China.
FAU - Chen, Zhihui
AU  - Chen Z
FAU - Gu, Jun
AU  - Gu J
FAU - Wan, Mobin
AU  - Wan M
FAU - Shen, Qian
AU  - Shen Q
FAU - Kieny, Marie-Paule
AU  - Kieny MP
FAU - He, Jia
AU  - He J
FAU - Li, Zhen
AU  - Li Z
FAU - Zhang, Qingfeng
AU  - Zhang Q
FAU - Reed, Zarifah Hussain
AU  - Reed ZH
FAU - Zhu, Yongmei
AU  - Zhu Y
FAU - Li, Wenjie
AU  - Li W
FAU - Cao, Yang
AU  - Cao Y
FAU - Qu, Li
AU  - Qu L
FAU - Cao, Zhifang
AU  - Cao Z
FAU - Wang, Qiang
AU  - Wang Q
FAU - Liu, Haitao
AU  - Liu H
FAU - Pan, Xuegong
AU  - Pan X
FAU - Huang, Xiudong
AU  - Huang X
FAU - Zhang, Dongmei
AU  - Zhang D
FAU - Xue, Xiangyang
AU  - Xue X
FAU - Pan, Weiqing
AU  - Pan W
LA  - eng
SI  - ISRCTN/ISRCTN66850051
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080409
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Membrane Proteins)
RN  - 0 (Merozoite Surface Protein 1)
RN  - 0 (Oleic Acids)
RN  - 0 (Protein Subunits)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (apical membrane antigen I, Plasmodium)
RN  - 25339-93-9 (mannide monooleate)
RN  - 3OWL53L36A (Mannitol)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Antigens, Protozoan/*chemistry
MH  - Female
MH  - Humans
MH  - Malaria Vaccines/*chemistry/pharmacology
MH  - Malaria, Falciparum/*prevention & control
MH  - Male
MH  - Mannitol/*analogs & derivatives/chemistry/pharmacology
MH  - Membrane Proteins/*chemistry
MH  - Merozoite Surface Protein 1/*chemistry
MH  - Middle Aged
MH  - Oleic Acids/*chemistry/pharmacology
MH  - Plasmodium falciparum/*metabolism
MH  - Protein Subunits/*chemistry
MH  - Protozoan Proteins/*chemistry
MH  - Recombinant Fusion Proteins/chemistry
MH  - Safety
PMC - PMC2276862
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2008/04/10 09:00
MHDA- 2008/06/11 09:00
PMCR- 2008/04/09
CRDT- 2008/04/10 09:00
PHST- 2007/10/04 00:00 [received]
PHST- 2008/02/28 00:00 [accepted]
PHST- 2008/04/10 09:00 [pubmed]
PHST- 2008/06/11 09:00 [medline]
PHST- 2008/04/10 09:00 [entrez]
PHST- 2008/04/09 00:00 [pmc-release]
AID - 07-PONE-CT-02409R1 [pii]
AID - 10.1371/journal.pone.0001952 [doi]
PST - epublish
SO  - PLoS One. 2008 Apr 9;3(4):e1952. doi: 10.1371/journal.pone.0001952.