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
- Author(s)
- John, CC; O'Donnell, RA; Sumba, PO; Moormann, AM; de Koning-Ward, TF; King, CL; Kazura, JW; Crabb, BS;
- Details
- Publication Year 2004-07-01,Volume 173,Issue #1,Page 666-672
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- The C-terminal 19-kDa fragment of Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) 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-1(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.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- HUMORAL IMMUNE-RESPONSES; C-TERMINAL FRAGMENT; GROWTH IN-VITRO; SERUM ANTIBODIES; WESTERN KENYA; VACCINE; RECOGNIZE; HIGHLANDS; EFFICACY; ANTIGEN
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Creation Date: 2004-07-01 12:00:00