A Plasmodium falciparum GLURP–MSP3 chimeric protein; expression in Lactococcus lactis, immunogenicity and induction of biologically active antibodies

Plasmodium falciparum malaria is a major cause of morbidity and mortality worldwide. To evaluate the efficacy of a possible vaccine antigen against P. falciparum infection, a fusion protein, derived from P. falciparum Glutamate-rich protein (GLURP) genetically coupled to P. falciparum Merozoite surf...

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Veröffentlicht in:Vaccine 2004-03, Vol.22 (9), p.1188-1198
Hauptverfasser: Theisen, Michael, Soe, Soe, Brunstedt, Katja, Follmann, Frank, Bredmose, Lars, Israelsen, Hans, Madsen, Søren M, Druilhe, Pierre
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Sprache:eng
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Zusammenfassung:Plasmodium falciparum malaria is a major cause of morbidity and mortality worldwide. To evaluate the efficacy of a possible vaccine antigen against P. falciparum infection, a fusion protein, derived from P. falciparum Glutamate-rich protein (GLURP) genetically coupled to P. falciparum Merozoite surface protein 3 (MSP3) was produced in Lactococcus lactis as a secreted recombinant GLURP–MSP3 fusion protein. The hybrid protein was purified to homogeneity by ion exchange and hydrophobic-interaction chromatography and its composition was verified by MALDI MS, SDS/PAGE and Western blotting with antibodies against antigenic components of GLURP and MSP3. Mice immunized with the hybrid protein produced higher levels of both GLURP- and MSP3-specific antibodies than mice immunized with either GLURP, MSP3 or a mix of both. The protective potential of the hybrid protein was also demonstrated by in vitro parasite-growth inhibition of mouse anti-GLURP–MSP3 IgG antibodies in a monocyte-dependent manner. These results indicate that the GLURP–MSP3 hybrid could be a valuable strategy for future P. falciparum vaccine development.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2003.09.017