Assessment of the role of the humoral response to Plasmodium falciparum MSP2 compared to RESA and SPf66 in protecting Papua New Guinean children from clinical malaria

Abstract

The prevalence and concentration of naturally acquired humoral response (IgG) to merozoite surface protein 2 (MSP2), RESA, SPf66 and crude schizont extract were measured in a population living in a malaria highly endemic area of Papua New Guinea. A prospective longitudinal study in 0.5-15 year old children was conducted for one year in order to examine the relationship between the humoral response to these antigens and subsequent susceptibility to clinical malaria using a series of clinical definitions. The prevalence and concentration of antibodies to all antigens increased with age. Such correlation with age was most marked for MSP2 recombinant proteins. When age and previous exposure were controlled for, only antibody levels to MSP2 recombinant proteins (3D7 and d3D7) and to RESA predicted a reduction in incidence rate of episodes of clinical malaria. Our results support the inclusion of the recombinant proteins of the 3D7 allelic family of merozoite surface antigen 2 and RESA into a subunit vaccine against malaria.

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

“…14,15,[39][40][41][42][43] The finding of diversity in all of these reinforces the difficulties of inducing protective responses capable of transcending strain differences. Immune selection would be consistent with the diversity seen in AMA1, 44 and inefficient antibody responses are elicited to the repeat regions of the other antigens studied.…”

High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

“…The genetic diversity of a parasite population is shaped by various influences, including genetic drift, mutation, natural selection, and gene flow. 40 MSP2 is the second most abundant protein on the surface of the merozoite 41 and a target of naturally acquired antibodies, 42,43 and therefore diversity is influenced by immune (balancing) selection. A comparison of msp2 diversity between Tanzania and PNG showed many more alleles (A = 76 and 35, respectively), however only slightly higher expected heterozygosity (H e = 0.933 and 0.965, respectively) in the African population where transmission is approximately ten times that of PNG.…”

Using Population Genetics to Guide Malaria Vaccine Design

“…MSP2 is a target of naturally acquired antibodies [123,124] and antibodies are associated with protection against clinical malaria in some studies [125][126][127][128]. Longitudinal studies have suggested allele-specific antibody responses, with encountered strains not being observed in subsequent infections [129,130], while others have shown that individuals can be re-infected with homologous strains [131].…”

“…For example, meta-analysis of studies investigating the protective effects of anti-MSP2 3D7 and MSP2 FC27 responses showed no evidence of a reduced risk of symptomatic P. falciparum (all strains combined) [192]. Four studies included allele-specific endpoints; two studies in PNG showed protective MSP2 responses to homologous strains [125,128] whereas studies in South America and Africa [193,194], show no evidence of a protective effect of pre-existing MSP2 allele-specific immunity on clinical episodes with homologous parasites.…”