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Age-related differences in naturally acquired T cell memory to Plasmodium falciparum merozoite surface protein 1.

ABSTRACT: Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual, age-related development of protection against high-density parasitemia and clinical malaria. Animal studies, and less commonly, observations of humans with malaria, suggest that T-cell responses are important in the development and maintenance of this immunity, which is mediated primarily by antibodies that slow repeated cycles of merozoites through erythrocytes. To advance our rather limited knowledge on human T-cell immunity to blood stage malaria infection, we evaluated CD4 and CD8 T-cell effector memory subset responses to the 42 kDa C-terminal fragment of Merozoite Surface Protein 1 (MSP1(42)), a malaria vaccine candidate, by 49 healthy 0.5 to ?18 year old residents of a holoendemic area in western Kenya. The proportion of individuals with peripheral blood mononuclear cell MSP1(42) driven IFN-? ELISPOT responses increased from 20% (2/20) among 0.5-1 year old children to 90% (9/10) of adults ?18 years (P?=?0.01); parallel increases in the magnitude of IFN-? responses were observed across all age groups (0.5, 1, 2, 5 and ?18 years, P?=?0.001). Less than 1% of total CD4 and CD8 T-cells from both children and adults produced IFN-? in response to MSP1(42). However, adults had higher proportions of MSP1(42) driven IFN-? secreting CD4 and CD8 effector memory (CD45RA(-) CD62L(-)) T-cells than children (CD4: 50.9% vs. 28.8%, P?=?0.036; CD8: 52.1% vs. 18.3%, respectively P?=?0.009). In contrast, MSP1(42) driven IFN-? secreting naïve-like, transitional (CD45RA(+) CD62L(+)) CD4 and CD8 cells were the predominant T-cell subset among children with significantly fewer of these cells in adults (CD4: 34.9% vs. 5.1%, P?=?0.002; CD8: 47.0% vs. 20.5%, respectively, P?=?0.030). These data support the concept that meaningful age-related differences exist in the quality of T-cell immunity to malaria antigens such as MSP1.

SUBMITTER: Chelimo K

PROVIDER: S-EPMC3174209 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Age-related differences in naturally acquired T cell memory to Plasmodium falciparum merozoite surface protein 1.

Chelimo Kiprotich K Embury Paula B PB Sumba Peter Odada PO Vulule John J Ofulla Ayub V AV Long Carole C Kazura James W JW Moormann Ann M AM

PloS one 20110916 9

Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual, age-related development of protection against high-density parasitemia and clinical malaria. Animal studies, and less commonly, observations of humans with malaria, suggest that T-cell responses are important in the development and maintenance of this immunity, which is mediated primarily by antibodies that slow repeated cycles of merozoites through erythrocytes. To advance ...[more]

PMID: 21935482

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Project description:Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

Project description:BackgroundNaturally acquired malaria immunity has many determinants and, in the absence of immunological markers of protection, studies assessing malaria incidence through clinical endpoints remain an approach to defining immunity acquisition. We investigated the role of age in disease incidence and the effects of chemoprophylaxis on clinical immunity development to Plasmodium falciparum during a randomised controlled trial.Methods and findingsA total of 415 Tanzanian infants were randomly assigned to receive weekly malaria prophylaxis with Deltaprim (3.125 mg of pyrimethamine plus 25 mg of dapsone) or placebo between the ages of 2 and 12 mo. Children were followed up until 4 y of age. Uncomplicated febrile malaria, severe malaria, and anaemia morbidity were assessed through hospital-based passive surveillance. Compared with the group of control participants, there was a marked reduction in the incidence of clinical malaria, severe malaria, and anaemia in the group of children who had received chemoprophylaxis during the first year of life. After discontinuing the intervention, there was a significant increase in the incidence of clinical malaria for 2 y. The cumulative rates of clinical malaria, by age 4 y, were slightly higher in the group of children who had previously received chemoprophylaxis: 3.22 episodes versus 3.02 episodes in the group of control participants; rate difference 0.20 (95% confidence interval [CI]: -0.21 to 0.59). By age 4 y, the cumulative rates of severe malaria, however, were slightly lower in chemosuppressed children (0.47 versus 0.59) (rate difference -0.12 [95% CI: -0.27 to 0.03]). The number of episodes of anaemia was also slightly lower in chemosuppressed children by age 4 y: 0.93 episodes (95% CI: 0.79 to 0.97) versus 1.12 episodes in the group of control participants (95% CI: 0.97 to 1.28) (rate difference -0.19 [95% CI: -0.40 to 0.01]), respectively.ConclusionsReducing exposure to P. falciparum antigens through chemoprophylaxis early in life can delay immunity acquisition. Infants appear to acquire immunity faster than older children, but have a higher risk of developing severe forms of malaria and anaemia. These findings provide insight on the interplay between immunity and exposure-reduction interventions.

Dataset Information

Age-related differences in naturally acquired T cell memory to Plasmodium falciparum merozoite surface protein 1.

Publications

Age-related differences in naturally acquired T cell memory to Plasmodium falciparum merozoite surface protein 1.

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