Abstract
BackgroundNaturally 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.MethodsBlood 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-142) was determined by IFN-γ 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-119 invasion inhibition antibodies (IIA) to the E-TSR (3D7) allele and growth inhibitory activity (GIA). The haplotype of MSP-119 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.ResultsMSP-1 IgG antibodies determined by serology were most consistent over time, followed by MSP-1 specific T cell IFN-γ responses and GIA. MSP-119 IIA showed the least stability over time. However, the level of MSP-119 specific IIA correlated with relatively higher rainfall and higher prevalence of P. falciparum infection with the MSP-119 E-TSR haplotype.ConclusionVariation 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.
Highlights
Acquired immunity to blood-stage Plasmodium falciparum infection develops with age and after repeated infections
growth inhibitory activity (GIA) appears to be moderately stable over time intervals as long as six months. 3D7 merozoite surface protein (MSP)-119specific inhibition antibodies (IIA) demonstrates fair stability at three-week intervals that disappears at longer time intervals
Based on serial observations of 16 adult residents of western Kenya examined over a ninemonth period, these results show that 1) IFN-γ responses to 3D7 MSP-142 are fair to moderately stable; 2) IgG antibodies to the FVO and 3D7 alleles of MSP-142 measured serologically by ELISA are most stable over time; and 3) functional measures of MSP-119 specific IIA is a transient but potentially sensitive indicator of antibody-mediated immunity that may reflect recent exposure to P. falciparum with the corresponding MSP-119 haplotype
Summary
Acquired immunity to blood-stage Plasmodium falciparum infection develops with age and after repeated infections. Individuals living in areas where transmission of Plasmodium falciparum is intense and stable develop naturally acquired immunity that is characterized by a high degree of protection against high-density parasitaemia and clinical illness. There have been fewer descriptions of how T cell immunity to blood stage antigens varies over time [1316], and whether T cell and antibody responses are concordant in the same individuals An appreciation of this aspect of naturally acquired immunity is important to the identification and interpretation of immune assays that may be used as primary and secondary endpoints in clinical vaccine trials that assess immunogenicity and protective efficacy in malaria endemic populations
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