Article

The Breadth, but Not the Magnitude, of Circulating Memory B Cell Responses to P. falciparum Increases with Age/Exposure in an Area of Low Transmission

Medical Research Council Laboratories, Fajara, Banjul, The Gambia.
PLoS ONE (Impact Factor: 3.23). 10/2011; 6(10):e25582. DOI: 10.1371/journal.pone.0025582
Source: PubMed

ABSTRACT

Malaria caused by Plasmodium falciparum remains a major cause of death in sub-Saharan Africa. Immunity against symptoms of malaria requires repeated exposure, suggesting either that the parasite is poorly immunogenic or that the development of effective immune responses to malaria may be impaired.
We carried out two age-stratified cross-sectional surveys of anti-malarial humoral immune responses in a Gambian village where P. falciparum malaria transmission is low and sporadic. Circulating antibodies and memory B cells (MBC) to four malarial antigens were measured using ELISA and cultured B cell ELISpot.
The proportion of individuals with malaria-specific MBC and antibodies, and the average number of antigens recognised by each individual, increased with age but the magnitude of these responses did not. Malaria-specific antibody levels did not correlate with either the prevalence or median number of MBC, indicating that these two assays are measuring different aspects of the humoral immune response. Among those with immunological evidence of malaria exposure (defined as a positive response to at least one malarial antigen either by ELISA or ELISPOT), the median number of malaria-specific MBC was similar to median numbers of diphtheria-specific MBC, suggesting that the circulating memory cell pool for malaria antigens is of similar size to that for other antigens.

Download full-text

Full-text

Available from: Edmond Joseph Remarque
  • Source
    • "Similarly, memory B cells specific for one or more malarial antigens have been reported to be maintained for more than a decade in individuals with a history of acute malaria following travel but have since lived in the complete absence of infection (Ndungu et al. 2013), suggesting that parasite-specific memory B cells can be generated and sustained without repeated exposure. Furthermore, memory B cell responses to different malaria antigens can be induced at a similar magnitude to vaccine antigenspecific responses in The Gambia, where malaria transmission is low and sporadic (Nogaro et al. 2011). Collectively, these findings suggest that variable transmission levels might affect the acquisition and maintenance of memory B cells, and lend weight to the notion that frequent clinical malaria episodes could have a detrimental effect in the generation of immunologic B cell memory. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Malaria is one of the most serious infectious diseases with ~250 million clinical cases annually. Most cases of severe disease are caused by Plasmodium falciparum . The blood stage of Plasmodium parasite is entirely responsible for malaria-associated pathology. Disease syndromes range from fever to more severe complications, including respiratory distress, metabolic acidosis, renal failure, pulmonary oedema and cerebral malaria. The most susceptible population to severe malaria is children under the age of 5, with low levels of immunity. It is only after many years of repeated exposure, that individuals living in endemic areas develop clinical immunity. This form of protection does not result in sterilizing immunity but prevents clinical episodes by substantially reducing parasite burden. Naturally acquired immunity predominantly targets blood-stage parasites and it is known to require antibody responses. A large body of epidemiological evidence suggests that antibodies to Plasmodium antigens are inefficiently generated and rapidly lost in the absence of ongoing exposure, which suggests a defect in the development of B cell immunological memory. This review summarizes the main findings to date contributing to our understanding on cellular processes underlying the slow acquisition of humoral immunity to malaria. Some of the key outstanding questions in the field are discussed.
    Full-text · Article · Jan 2016 · Parasitology
  • Source
    • "The intensity of antibody response to P. falciparum is significantly lower amongst residents of the low transmission hilltop site compared to the valley bottom where transmission is more stable. Although those previous studies did not compare the breadth of antibody responses between the sites, we found that there was significant difference in the number of antigens recognized by sera from the different sites but only amongst the youngest age group, confirming previous findings that repeated parasite exposure expands the repertoire of antibodies as children grow older [14,16], and is associated with protection from disease in adults [64]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Malaria represents a major public health problem in Africa. In the East African highlands, the high-altitude areas were previously considered too cold to support vector population and parasite transmission, rendering the region particularly prone to epidemic malaria due to the lack of protective immunity of the population. Since the 1980's, frequent malaria epidemics have been reported and these successive outbreaks may have generated some immunity against Plasmodium falciparum amongst the highland residents. Serological studies reveal indirect evidence of human exposure to the parasite, and can reliably assess prevalence of exposure and transmission intensity in an endemic area. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasite's antigens. We surveyed and compared the antibody response profiles of age-stratified sera from residents of two endemic areas in the western Kenyan highlands with differing malaria transmission intensities, during two distinct seasons, against 854 polypeptides of P. falciparum using high-throughput proteomic microarray technology. We identified 107 proteins as serum antibody targets, which were then characterized for their gene ontology biological process and cellular component of the parasite, and showed significant enrichment for categories related to immune evasion, pathogenesis and expression on the host's cell and parasite's surface. Additionally, we calculated age-fitted annual seroconversion rates for the immunogenic proteins, and contrasted the age-dependent antibody acquisition for those antigens between the two sampling sites. We observed highly immunogenic antigens that produce stable antibody responses from early age in both sites, as well as less immunogenic proteins that require repeated exposure for stable responses to develop and produce different seroconversion rates between sites. We propose that a combination of highly and less immunogenic proteins could be used in serological surveys to detect differences in malaria transmission levels, distinguishing sites of unstable and stable transmission.
    Full-text · Article · Dec 2013 · PLoS ONE
  • Source
    • "It appears that frequent reinfection is required to maintain high levels of circulating Ab, thus in highly endemic areas Ab levels are stable [36,37], but in low or unstable transmission areas Ab levels diminish quickly after an infection [28,38], showing seasonal variation [26,27,39–41]. Conversely, memory B cells (MBC) can persist with reduced transmission [42–45]. However, a study reported the presence of Ab, but only very low frequencies of malaria-specific MBC in children, suggesting a low induction of malaria-specific circulating MBC as a reason for short-lived anti-malarial Ab responses [46]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or without malaria (n=37), naïve adults (travelers) with a first clinical malaria episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-142 (3D7 and FVO strains), EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry. Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026), but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-142 (P≤0.015), similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001), both with malaria. Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its effect on protection, with important implications for future vaccine design and public health control measures.
    Full-text · Article · Aug 2013 · PLoS ONE
Show more