2007

2007. old). However, antibodies to merozoite surface protein 2 were shorter lived than antibodies to other antigens and were not N-Desethyl Sunitinib more persistent in older children. The age-specific and antigen-specific differences were not explained by different IgG subclass response profiles, indicating the probable importance of differential longevities of plasma cell populations rather than antibody molecules. It is likely that young children mostly have short-lived plasma cells and thus experience rapid declines in antibody levels but that older children have longer-lasting antibody responses that depend on long-lived plasma cells. Immunity to mild malaria is acquired after repeated infections, although the longevity of the relevant components of the immune response that mediate this protection needs to be better determined (31). Passive transfer experiments have shown the importance of antibodies against blood-stage parasites in serum, and there are epidemiological associations between antibodies to particular antigens and protection from malaria, with some discrimination between those antibodies that Egfr are likely to be protective and those that are simply covariate N-Desethyl Sunitinib (15, 27). Levels of naturally acquired antibodies to antigens in sera have been shown previously to peak and decline rapidly after clinical malaria infections in young children (1, 7, N-Desethyl Sunitinib 18, 19, 23). It is possible that the clearance of antibodies is particularly rapid during the resolution of a clinical malaria episode, and it is important that studies of antibody decline be conducted also with asymptomatic individuals who have previously resolved their infections. A model to explain cross-sectional age-specific serological profiles indicates that low levels of antibodies may be maintained for many years after infection (11), and early studies using crude malaria antigen preparations also indicated that antibodies can be detected for some years after infection (4, 9). Antibody-secreting plasma cells can be short or long lived. Both types can be generated in the germinal center, and short-lived plasma cells can also be generated in the T-cell-rich extrafollicular regions. Short-lived plasma cells need to be replenished from a memory B-cell population, but long-lived plasma cells survive and secrete antibody for extended N-Desethyl Sunitinib periods independently (20, 30). The longevity of antibody responses in the absence of continued antigenic presentation may provide an indication of the plasma cell populations responsible for antibody secretion. To study the longevity of naturally acquired antibody responses to malaria antigens, children of up to 6 years of age in The Gambia were recruited into two longitudinal study cohorts and monitored during annual dry seasons when there was no detectable malaria transmission. We examined the duration of naturally acquired antibody responses to merozoite antigens apical merozoite antigen 1 (AMA1), erythrocyte binding antigen 175 (EBA175), merozoite surface protein 1 (MSP1), and MSP2, for which vaccine constructs have been developed and are under preclinical development or clinical testing (29, 34), as well as crude schizont extract. Associations among the longevity of antibody responses and the persistence of parasites, the ages of children, residential locations, and ethnicities were examined, as well as differences among the antigens. MATERIALS AND METHODS Study area. Samples were collected during the dry months of 2003 and 2004 from children under 74 weeks of age living in The Gambia in the town of Farafenni and surrounding villages, an area situated approximately 130 km from your coast. Rainfall and the transmission of malaria are very rare during the dry time of year between November and June, so the study was conducted during this time of year in two different years when the risk of incident infections was minimal. Each year, consultations and open meetings with community leaders and traditional rulers were held to obtain community-wide consent prior to inviting N-Desethyl Sunitinib individual participation and educated consent. The studies were reviewed and authorized by the Medical Study Council Scientific Coordinating Committee and the Medical Study Council and Gambian Authorities Joint Ethics Committee. Dry time of year cohort 1 (December 2002 to June 2003). At the beginning of the dry time of year in December 2002, 129 children under 6 years of age whose parents offered written educated consent after the study and procedure were explained were enrolled for any prospective study of antibody levels. A finger prick blood sample (minimum of 200 l) was collected from each child for the preparation of serum samples and thick-blood-smear slides. Later on, during April, May, and June in the 2003 dry time of year, the children were went to every 2 weeks and a finger prick blood sample.