Immunisation with recombinant AMA-1 protects mice against infection with Plasmodium chabaudi
Autor: | S J Edwards, David Pye, Mary L.S.M. Matthew, Robin F. Anders, P E Crewther, Mai B. Margetts, Bronwyn Pollock |
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Rok vydání: | 1998 |
Předmět: |
Protozoan Proteins
Antibodies Protozoan Antigens Protozoan Microbiology Plasmodium chabaudi Mice Antigen Malaria Vaccines parasitic diseases Animals Apical membrane antigen 1 Mice Inbred BALB C Mice Inbred C3H General Veterinary General Immunology and Microbiology biology Immunogenicity Public Health Environmental and Occupational Health Membrane Proteins Apical membrane biology.organism_classification Virology Recombinant Proteins Malaria Infectious Diseases Rhoptry neck Ectodomain Plasmodium knowlesi Molecular Medicine |
Zdroj: | Vaccine. 16:240-247 |
ISSN: | 0264-410X |
DOI: | 10.1016/s0264-410x(97)88331-4 |
Popis: | The Plasmodium merozoite surface antigen apical membrane antigen-1 (AMA-1) has previously been shown to provide partial protection to Saimiri and rhesus monkeys immunised with recombinant Plasmodium fragile or parasite-derived Plasmodium knowlesi AMA-1, respectively. In the study reported here we have used the Plasmodium chabaudi/mouse model system to extend our pre-clinical assessment of an AMA-1 vaccine. We describe here the expression of the full-length Plasmodium chabaudi adami AMA-1 and the P. chabaudi adami AMA-1 ectodomain using both baculovirus and Escherichia coli. The ectodomain expressed in E. coli, which contained an N-terminal hexa-his tag, was purified by Ni-chelate chromatography and refolded in vitro in the presence of oxidised and reduced glutathione to generate intramolecular disulphide bonds. In a series of vaccine trials, in both inbred and outbred mice, highly significant protection was obtained by immunising with the refolded AMA-1 ectodomain. Protection was shown to correlate with antibody response and was dependent on intact disulphide bonds. Passive transfer of antibodies raised in rabbits against the refolded AMA-1 ectodomain was also protective. In view of this demonstration that E. coli expression of a soluble P. chabaudi AMA-1 domain can generate a vaccine that is effective in mice, we are pursuing a similar approach to generating a vaccine against P. falciparum for testing in human volunteers. |
Databáze: | OpenAIRE |
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