[PDF][PDF] IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria …

RR Taylor, SJ Allen, BM Greenwood… - The American journal of …, 1998 - Citeseer
RR Taylor, SJ Allen, BM Greenwood, EM Riley
The American journal of tropical medicine and hygiene, 1998Citeseer
In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium
falciparum malaria is endemic with seasonal transmission, 178 individuals 1–75 years of
age were assessed for their antibody response to the malaria vaccine candidate, merozoite
surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length,
repetitive, and group-specific domains of both allelic families of MSP2 was determined by
ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence …
Abstract
In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1–75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3–8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.
In areas with stable endemic Plasmodium falciparum malaria transmission, parasitemia is most common in young children, with the incidence of parasitemia decreasing steadily with age. The precise timing of events depends on local patterns of malaria transmission and levels of endemicity. In The Gambia, where transmission is seasonal but stable from year to year, parasite rates do not begin to decrease until 10–12 years of age, whereas the incidence of clinical disease peaks at six years of age; in the same population, peak mortality from malaria occurs in children four years of age. 1 Various factors are thought to contribute to the slow development of immunity to malaria. Many malaria antigens are antigenically diverse and it has been proposed that protective immunity is dependent upon cumulative exposure to the many parasite variants circulating in the local population. 2 Critical malaria antigens may be poorly immunogenic and immunologic nonresponsiveness may be the result of parasite antigens evolving, presenting limited T cell epitopes to the immune system and thus failing to give T cell help for antibody production. 3 It has also been proposed that host age itself is a determinant of naturally acquired immunity such that protection is governed by a relatively brief heavy exposure and some intrinsic immune factor (s) associated with the age of the host. 4 However, this hypothesis cannot easily be demonstrated in populations from malaria endemic areas where age and exposure are directly related. It is becoming apparent that the functional specificity of antibodies to malaria antigens may play an important role in the protective immune response. 5–8 In vivo protective immunity to malaria correlates with in vitro inhibition of parasite growth by immune IgG in the presence of blood monocytes. 5, 7 If ancillary cells are required for antibody-mediated immunity, the isotype or subclass of the relevant antibodies is an important variable to consider; an individual may not be protected until there are sufficient levels of antibodies of …
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