Merozoite
surface proteins (MSPs) are critical for parasite invasion; they represent attractive targets for antibody-based protection against clinical
malaria. To identify protection-associated target MSPs, the present study analysed antibody responses to whole merozoite extract (ME) and to defined MSP recombinant
antigens in hospitalized patients from a low endemic urban area as a function of disease severity (mild versus
cerebral malaria). Sera from 110 patients with confirmed severe
cerebral malaria (CM) and 91 patients with mild
malaria (MM) were analysed (mean age = 29 years) for total and subclass
immunoglobulin (Ig)G to ME and total
IgG to MSP1p19, MSP2, MSP3, MSP4 and MSP5 by
enzyme-linked
immunosorbent assay (ELISA). Functional antibody responses were evaluated using the antibody-dependent respiratory burst (ADRB) assay in a subset of sera. There was a trend towards higher
IgG1 and
IgG4 levels to ME in CM compared to MM; only ME
IgM responses differed significantly between fatal and surviving CM patients. Increased prevalence of
IgG to individual MSPs was found in the CM compared to the MM group, including significantly higher levels of
IgG to MSP4 and MSP5 in the former. Sera from fatal (24·5%) versus surviving cases showed significantly lower
IgG to MSP1p19 and MSP3 (P < 0·05). ADRB assay readouts correlated with high levels of anti-MSP
IgG, and trended higher in sera from patients with surviving compared to fatal CM outcome (P = 0·07). These results document strong differential antibody responses to MSP
antigens as targets of protective immunity against CM and in particular MSP1p19 and MSP3 as prognostic indicators.