Comparison of the protective efficacy of yeast-derived and Escherichia coli-derived recombinant merozoite surface protein 4/5 against lethal challenge by Plasmodium yoelii

The gene encoding the Plasmodium yoelii homologue of P. falciparum merozoit e surface proteins 4 (MSP4) and 5 (MSP5) has been expressed in Escherichia coli and Saccharomyces cerevisiae. The protein contains a single epidermal growth factor (EGF)-like domain and is expressed in a form lacking the pred icted N-terminal signal and glycosyl phosphatidylinositol (GPI) attachment sequences. The recombinant protein derived from E. coli (EcMSP4/5) was high ly effective at protecting mice against lethal challenge with 10(5) parasit es of the P. yoelii YM strain. In contrast, the protective efficacy of yeas t-derived MSP4/5 (yMSP4/5) was considerably less. The antibody titres in bo th groups were significantly different with mice immunised with yeast-deriv ed protein showing significantly lower pre-challenge antibody responses. Th ere was a significant inverse correlation between antibody levels as measur ed by ELISA and peak parasitaemia. Mice immunised with EcMSP4/5 produced an ti-PyMSP4/5 antibodies predominantly of the IgG2a and IgG2b isotypes, where as, mice immunised with yMSP4/5 mainly produced antibodies of the IgG1 isot ype. The differences in antibody titres and subtype distribution may accoun t for the observed differences in protective efficacy of these protein prep arations. Levels of protective efficacy of MSP4/5 were compared with that o btained using P. yoelii MSPI produced in S. cerevisiae. Levels of protectio n induced by E. coh derived MSP4/5 were superior to those induced by MSPI w hich in turn were better than those induced by yeast-derived MSP4/5. (C) 20 01 Elsevier Science Ltd. All rights reserved.