A Phase 1 Trial of MSP 2-C 1 , a Blood-Stage Malaria Vaccine Containing 2 Isoforms of MSP 2 Formulated with Montanide H ISA 720

Background: In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2), parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naı̈ve adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27), formulated in equal amounts with MontanideH ISA 720 as a water-in-oil emulsion. Methodology/Principal Findings: The trial was designed to include three dose cohorts (10, 40, and 80 mg), each with twelve subjects receiving the vaccine and three control subjects receiving MontanideH ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 mg dose; no subjects received the 80 mg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 mg and 40 mg dose cohorts, with antibody levels by ELISA higher in the 40 mg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced antiMSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI) of parasite growth. Conclusions/Significance: As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this formulation, further clinical development of MSP2-C1 will require formulation of MSP2 in an alternative adjuvant. Trial Registration: Australian New Zealand Clinical Trials Registry 12607000552482 Citation: McCarthy JS, Marjason J, Elliott S, Fahey P, Bang G, et al. (2011) A Phase 1 Trial of MSP2-C1, a Blood-Stage Malaria Vaccine Containing 2 Isoforms of MSP2 Formulated with MontanideH ISA 720. PLoS ONE 6(9): e24413. doi:10.1371/journal.pone.0024413 Editor: David Joseph Diemert, The George Washington University Medical Center, United States of America Received February 25, 2011; Accepted August 10, 2011; Published September 19, 2011 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: The trial was funded by PATH-MVI. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. JMC is supported by an NHMRC Practitioner Fellowship and a Queensland Health Research Fellowship. JGB was supported by a Career Development Award from the National Health and Medical Research Council, and a Future Fellowship from the Australian Research Council. Carole Long was supported in part by the intramural program of the National Institute of Allergy and Infectious Diseases, NIH. The GIA Reference Center at NIH is supported by the PATH-Malaria Vaccine Initiative. Competing Interests: PF, EM and ET were employees of the trial funder PATH-MVI at the time that the trial was undertaken. Authors JM, SE and HAH are employed by a commercial company, Q-Pharm Pty Ltd. These conflicts do not alter the authors’ adherence to all the PLoS ONE policies on sharing data and material. * E-mail: J.McCarthy@uq.edu.au