Assessment of the Role of Naturally Acquired Antibody Levels to Plasmodium falciparum Merozoite Surface Protein-1 in Protecting Papua New Guinean Children from Malaria Morbidity

Abstract

We investigated the prevalence and magnitude of naturally acquired humoral immune response to the major merozoite surface protein (MSP-1) in a malaria-endemic population in Papua New Guinea. A prospective longitudinal study in 0.5-15-year-old children was conducted for one year to examine the relationship between acquired immune response to MSP-1 and subsequent susceptibility to clinical disease. The prevalence and concentration of antibodies to both N-(195A) and C-terminal (BVp42) regions of MSP-1 as well as to the parasite-derived MSP-1 increased with age, with the highest prevalence and concentration of antibodies being detected for the parasite-derived MSP-1 molecule and the C-terminal region of MSP-1. As malaria morbidity decreases with age, a significant negative correlation was observed between antibody levels to both 195A and BVp42 and the incidence rate of clinical malaria. When age and past exposure were corrected for, only antibody concentrations against BVp42 and to a lesser extent parasite-derived MSP-1 were significantly associated with protection from clinical malaria and severe parasitemia. The reduction in the incidence rate of clinical malaria observed in individuals with high antibody concentration to MSP-1 may be due to antibodies directed against epitopes within the C-terminal region of MSP-1.

Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.

“…A higher seroprevalence was reported for RESA, another IRBC membrane-associated antigen and for merozoite antigens, such as merozoite surface protein-1 (MSP-1) or apical membrane antigen-1 (AMA-1). [24][25][26][27] Whether the lower prevalence observed here reflects restricted immunogenicity of the R23, PfEB200, and GST-5 antigenic determinants is unclear. It is possible that the positivity threshold used underestimated the seroprevalence.…”

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

“…14,15,[39][40][41][42][43] The finding of diversity in all of these reinforces the difficulties of inducing protective responses capable of transcending strain differences. Immune selection would be consistent with the diversity seen in AMA1, 44 and inefficient antibody responses are elicited to the repeat regions of the other antigens studied.…”

Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

“…mAbs to MSP-1 have been found to inhibit in vitro growth of parasites (33,34). Ab levels to MSP-1 19 correlate with age-related changes in the level of asexual parasitemia in some, but not all malaria endemic areas (35)(36)(37)(38)(39)(40)(41). Primate vaccine trials (42,43) and studies of mouse malaria models indicate that immunization with MSP-1 19 (44,45) protects against blood-stage infection.…”