Antibody responses to polymorphic Plasmodium falciparum merozoite antigens in Malawian children with severe and uncomplicated malaria.

BACKGROUND

The magnitude and specificity of naturally acquired antibody responses to Plasmodium falciparum merozoite surface proteins could influence the clinical presentation of malaria in young children. As many putative targets of immunity are structurally diverse, lack of antibodies to the infective parasite genotype could lead to immune evasion, higher parasitaemia and more severe clinical manifestation of the disease.

METHODS

The degree of concordance between IgG responses to polymorphic and dimorphic antigenic regions of vaccine candidates MSP-1 and MSP-2 and the infective parasites detected by PCR was investigated in 269 paediatric patients presenting with cerebral malaria (CM), severe malarial anaemia (SMA) or uncomplicated malaria (UM) in Blantyre, Malawi.

RESULTS

Overall, the specificities of antibodies matched the infecting P. falciparum genotypes, more so at convalescence, although levels generally decreased after parasite clearance. At presentation, no evidence that children with severe malaria (SM) had lower concentrations of antibodies matching parasite genotypes, defined by polymorphic MSP-1 block 2 alleles, than children with UM, was found. However, a lower IgG response to MSP-2 type B (FC27) correlated with CM while a lower response to MSP-2 type A (IC1/3D7) parasites correlated with SMA. In addition, discordant antibody-genotype responses were associated with neurological sequelae after CM compared to full recovery.

CONCLUSIONS

Although antibody specificities were generally concordant with the genotyped parasites, UM patients tended to have a higher proportion of antibody responses matching the dimorphic MSP-2 parasite genotypes than SM patients, and thus antigenic diversity of blood stage antigens could contribute to immune escape and malaria severity.