Temporal stability of naturally acquired immunity to Merozoite Surface Protein-1 in Kenyan adults

Abstract

BACKGROUND: Naturally acquired immunity to blood-stage Plasmodium falciparum infection develops with age and after repeated infections. In order to identify immune surrogates that can inform vaccine trials conducted in malaria endemic populations and to better understand the basis of naturally acquired immunity it is important to appreciate the temporal stability of cellular and humoral immune responses to malaria antigens. METHODS: Blood samples from 16 adults living in a malaria holoendemic region of western Kenya were obtained at six time points over the course of 9 months. T cell immunity to the 42 kDa C-terminal fragment of Merozoite Surface Protein-1 (MSP-1(42)) was determined by IFN-gamma ELISPOT. Antibodies to the 42 kDa and 19 kDa C-terminal fragments of MSP-1 were determined by serology and by functional assays that measure MSP-1(19) invasion inhibition antibodies (IIA) to the E-TSR (3D7) allele and growth inhibitory activity (GIA). The haplotype of MSP-1(19) alleles circulating in the population was determined by PCR. The kappa test of agreement was used to determine stability of immunity over the specified time intervals of 3 weeks, 6 weeks, 6 months, and 9 months. RESULTS: MSP-1 IgG antibodies determined by serology were most consistent over time, followed by MSP-1 specific T cell IFN-gamma responses and GIA. MSP-1(19) IIA showed the least stability over time. However, the level of MSP-1(19) specific IIA correlated with relatively higher rainfall and higher prevalence of P. falciparum infection with the MSP-1(19) E-TSR haplotype. CONCLUSION: Variation in the stability of cellular and humoral immune responses to P. falciparum blood stage antigens needs to be considered when interpreting the significance of these measurements as immune endpoints in residents of malaria endemic regions.