Evidence That Invasion-Inhibitory Antibodies Specific for the 19-kDa Fragment of Merozoite Surface Protein-1(MSP-1_(19))Can Play a Protective Role against Blood-Stage Plasmodium falciparum Infection in Individuals in a Malaria Endemic Area of Africa

摘要

The C-terminal 19-kDa fragment of Plasmodium falciparum merozoite surface protein-1(MSP-119)is a target of protective Abs against blood-stage infection and a leading candidate for inclusion in a human malaria vaccine.However,the precise role,relative importance,and mechanism of action of Abs that target this protein remain unclear.To examine the potential protective role of Abs to MSP-1_(19)in individuals naturally exposed to malaria,we conducted a treatment time to infection study over a 10-wk period in 76 residents of a highland area of western Kenya during a malaria epidemic.These semi-immune individuals were not all equally susceptible to reinfection with P.falciparum following drug cure.Using a new neutralization assay based on transgenic P.falciparum expressing the P.chabaudi MSP-1_(19)orthologue,individuals with high-level MSP-l_(19)-specific invasion-inhibitory Abs(>75th percentile)had a 66% reduction in the risk of blood-stage infection relative to others in the population(95% confidence interval,3-88%).In contrast,high levels of MSP-1_(19)IgG or IgG subclass Abs measured by enzyme immunoassay with six different recombinant MSP-1_(19)Ags did not correlate with protection from infection.IgG Abs measured by serology and functional invasion-inhibitory activity did not correlate with each other.These findings implicate an important protective role for MSP-1_(19)-specific invasion inhibitory Abs in immunity to blood-stage P.falciparum infection,and suggest that the measurement of MSP-1_(19)specific inhibitory Abs may serve as an accurate correlate of protection in clinical trials of MSP-1-based vaccines.