Merozoite surface protein MSP2 is avaccine candidate antigen of Plasmodium falciparum that is polymorphic in natural populations. In this study we aimed to investigate whether malaria infection in associated with anti-malaria specific IgG, using recombinant proteins derived from the two major allelic types of MSP2 and ABO blood group. The conclusion is the Higher anti-malarial IgG1, IgG3, IgG2 and lower levels of IgG4 were associated with reduced risk of malaria infection. IgG2 is activator of the classical complement pathway, Fc?RIIa H131 is essential for handling IgG2 immune complexes. These data suggest that an MSP2 based vaccine should be designed to induce high level antibody responses against the different MSP2 types present globally in P. falciparum populations and that MSP2 could be combined with other P. falciparum antigens to form a multi-component malaria vaccine.