The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 of<i>Plasmodium falciparum</i>Strain FVO Expressed in<i>Escherichia coli</i>Protects<i>Aotus nancymai</i>against Challenge with Homologous Erythrocytic-Stage Parasites

  • Christian A. Darko
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring
  • Evelina Angov
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring
  • William E. Collins
    Division of Parasitic Diseases, Centers for Disease Control and Prevention, Chamblee, Georgia
  • Elke S. Bergmann-Leitner
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring
  • Autumn S. Girouard
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring
  • Stacy L. Hitt
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring
  • Jana S. McBride
    School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland
  • Carter L. Diggs
    USAID Malaria Vaccine Development Program, U.S. Agency for International Development, Washington, D.C.
  • Anthony A. Holder
    Division of Parasitology, National Institute for Medical Research, London, United Kingdom
  • Carole A. Long
    Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland
  • John W. Barnwell
    Division of Parasitic Diseases, Centers for Disease Control and Prevention, Chamblee, Georgia
  • Jeffrey A. Lyon
    Department of Immunology, Walter Reed Army Institute of Research, Silver Spring

抄録

<jats:title>ABSTRACT</jats:title><jats:p>A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP1<jats:sub>42</jats:sub>gene fragment from the Vietnam-Oak Knoll (FVO) strain of<jats:italic>Plasmodium falciparum</jats:italic>was expressed as a soluble protein in<jats:italic>Escherichia coli</jats:italic>and purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised against<jats:italic>P. falciparum</jats:italic>malaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinating<jats:italic>Aotus nancymai</jats:italic>monkeys and challenging them with homologous<jats:italic>P. falciparum</jats:italic>FVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen of<jats:italic>Plasmodium vivax</jats:italic>, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP1<jats:sub>42</jats:sub>(FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced by<jats:italic>E. coli</jats:italic>MSP1<jats:sub>42</jats:sub>were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the<jats:italic>E. coli</jats:italic>MSP1<jats:sub>42</jats:sub>antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP1<jats:sub>42</jats:sub>, but not the MSP1<jats:sub>42</jats:sub>protein itself or the EGF-like domain 1 fragment. Soluble MSP1<jats:sub>42</jats:sub>(FVO) expressed in<jats:italic>E. coli</jats:italic>offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.</jats:p>

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