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Abstract: Merozoite surface protein 1 (MSP1) of Plasmodium falciparum has been implicated as an important target of acquired immunity, and candidate components for a vaccine include polymorphic epitopes in the N-terminal polymorphic block 2 region. We designed a polyvalent hybrid recombinant protein incorporating sequences of the three major allelic types of block 2 together with a composite repeat sequence of one of the types and N-terminal flanking T cell epitopes, and compared this with a series of recombinant proteins containing modular sub-components and similarly expressed in Escherichia coli. Immunogenicity of the full polyvalent hybrid protein was tested in both mice and rabbits, and comparative immunogenicity studies of the sub-component modules were performed in mice. The full hybrid protein induced high titre antibodies against each of the major block 2 allelic types expressed as separate recombinant proteins and against a wide range of allelic types naturally expressed by a panel of diverse P. falciparum isolates, while the sub-component modules had partial antigenic coverage as expected. This encourages further development and evaluation of the full MSP1 block 2 polyvalent hybrid protein as a candidate blood-stage component of a malaria vaccine. [Copyright &y& Elsevier]

To investigate relationships between Plasmodium falciparum parasitaemia, parasite genotypes, and specific anti-parasite antibodies, 244 school children (aged 4 to 16 years) were studied in April/May 2002, the peak malaria transmission season in Buea, Cameroon. Antibody reactivities were analysed by ELISA using an array of recombinant antigens representing different sequences from the polymorphic block 2 region of the merozoite surface protein 1 (MSP1), and the blood samples that were slide-positive for P. falciparum were genotyped for msp1 block 2 alleles. The prevalence of antibodies to the specific MSP1 block 2 antigens was significantly higher in children at one particular school (situated at the lowest altitude) compared to the others, although the prevalence of infection or particular parasite genotypes did not differ. Thus, at a population level, the prevalence of these antibodies does not simply reflect prevalence of parasites, but rather may be due to differences in the incidence of past infections. However, there were weak positive associations between specific antibody reactivity and the presence of the corresponding allele in the blood of individuals (statistically significant for the MAD20-type allele of block 2), indicating that antibody specificities are to some extent determined by current parasite infections. [Copyright &y& Elsevier]