Association between cellular response (IL‐4) to RESA/Pf155 and protection from clinical malaria among Papua New Guinean children living in a malaria endemic area

Al-Yaman, Fadwa; Genton, Blaise; Taraika, J.; Rf, Anders; Alpers, M. P.

doi:10.1046/j.1365-3024.1997.d01-204.x

Cited by 22 publications

(16 citation statements)

References 13 publications

(17 reference statements)

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“…Certainly, field studies suggest that antibodies to TRAP play a protective role, 28,29 but no studies have previously directly addressed the role of TRAP-specific T cells in naturally induced protection. Several studies have correlated protection with interleulin-4 (IL-4) or IL-10 release in response to various vaccine candidate antigens, 3,4 and the profile of other cytokines induced by TRAP may have influenced our results. Indeed, in a separate study, we found high levels of IL-10 reactivity to the same TRAP-derived peptides in coastal Kenyans (Flanagan KL and others, unpublished data).…”

Section: Discussionmentioning

confidence: 95%

Ex Vivo Interferon-Gamma Immune Response to Thrombospondin-Related Adhesive Protein in Coastal Kenyans: Longevity and Risk of Plasmodium Falciparum Infection

Flanagan

Mwangi

Plebanski³

et al. 2003

The American Journal of Tropical Medicine and Hygiene

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Abstract. Thrombospondin-related adhesive protein (TRAP) of Plasmodium falciparum is currently being tested in human vaccine studies. However, its natural reactivity in the field remains poorly characterized. More than 40% of 217 Kenyan donors responded in an ex vivo interferon-␥ (IFN-␥) enzyme-linked immunospot (ELISPOT) assay to at least one of 14 20mer peptides spanning 42% of the antigen. Reactivity was comparable from early childhood (>1 year of age) to old age, and the maximal precursor frequency of TRAP-specific cells to all 14 peptides was 1 in 4,000. Prospective follow-up for one year indicated that these low-level ex vivo responses to TRAP did not protect against the subsequent development of malaria. Retesting of selected donors after one year showed a complete change in the reactivity pattern, suggesting that malaria-specific ex vivo IFN-␥ ELISPOT assay responses are short lived in naturally exposed donors, even to conserved epitopes. This study provides important information regarding natural reactivity to a key malaria antigen.

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Section: Discussionmentioning

confidence: 95%

Ex Vivo Interferon-Gamma Immune Response to Thrombospondin-Related Adhesive Protein in Coastal Kenyans: Longevity and Risk of Plasmodium Falciparum Infection

Flanagan

Mwangi

Plebanski³

et al. 2003

The American Journal of Tropical Medicine and Hygiene

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“…Th2 cytokine production appears to be critical for the development of immunity to falciparum malaria. IL-4 levels have been shown to correlate with age, development of antibody to malaria antigen, and malaria protection and are believed to play a role in parasite clearance (1,15,30,33). CD4…”

Section: Discussionmentioning

confidence: 99%

Effects of ConcomitantSchistosoma haematobiumInfection on the Serum Cytokine Levels Elicited by AcutePlasmodium falciparumMalaria Infection in Malian Children

et al. 2006

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Polyparasitism is common in the developing world, and interactions that alter disease severity may occur. We previously demonstrated that infection with Schistosoma hematobium was associated with protection against Plasmodium falciparum infection in children who were 4 to 8 years old. In this study, we determined whether underlying helminth infections affected the cytokine responses to acute falciparum malaria. A total of 338 schistosomiasis-positive [Sch(؉)] children who were 4 to 14 years old were matched by age, residence, and sex with 338 schistosomiasis-negative [Sch(؊)] children and monitored for a malaria transmission season (25 weeks). Serologic cytokine levels were measured at the time of the first clinical malaria episode and in children who did not contract malaria. Elevated background levels of interleukin-6 (IL-6) (37.1 pg/ml versus 10.9 pg/ml [P ‫؍‬ 0.04]), IL-4 (27.7 pg/ml versus 6.9 pg/ml [P ‫؍‬ 0.02]), IL-10 (18.2 pg/ml versus 7.2 pg/ml [P < 0.001]), and gamma interferon (18.2 pg/ml versus 4.7 pg/ml [P ‫؍‬ 0.006]) were noted in Sch(؉) children compared to Sch(؊) children without malaria. IL-6 and IL-10 levels were elevated in association with acute malaria, but the levels appeared to be blunted in Sch(؉) children compared to Sch(؊) children who were 4 to 8 years old (for IL-6, 96.2 pg/ml versus 137.2 pg/ml [P ‫؍‬ 0.08]; for IL-10, 195.9 pg/ml versus 282.2 pg/ml [P ‫؍‬ 0.06]). The level of IL-10 was similarly lower in Sch(؉) children than in Sch(؊) children who were 9 to 14 years old (91.2 pg/ml versus 141.2 pg/ml [P ‫؍‬ 0.03]). IL-4 levels were inversely correlated with the time until the first malaria infection in both the Sch(؉) children (P < 0.001) and the Sch(؊) children (P < 0.001) who were 4 to 8 years old. We postulate that the Th2-enriched environment induced by schistosomiasis protects against malaria and alters the cytokine milieu during an actual infection.

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“…This confirms previous findings that proliferating, IFN-␥-and IL-4-producing cells frequently belong to functionally different subsets and emphasizes the importance of including measurements of several different T cell activities when screening donors for responsiveness to a given epitope. [34][35][36][37][38][39][40] Since the studies described here were performed with unseparated T cell preparations (i.e., mixed CD4 ϩ and CD8 ϩ cells), we can not exclude that functionally distinct CD8 ϩ cells were also stimulated. 41 These qualities will be further investigated by comparing T cell activation with phenotype characterization of the responding cells.…”

Section: Discussionmentioning

confidence: 99%

Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

Kulane

Siddique²,

Sarthou³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The B and T cell responses to EB200, a repetitive part of the Plasmodium falciparum antigen Pf332, were examined in malaria-exposed Senegalese adults. Most donors had high levels of antibodies to recombinant EB200 and 17 overlapping peptides spanning EB200. Taking proliferation and/or cytokine (interferon-␥ and interleukin-4) production as a measure of T cell activation, eight of the EB200-derived peptides induced responses in Ͼ 40% of the donors tested. There was no general association between the different types of T cell responses measured, emphasizing the importance of including multiple parameters when analyzing T cell responses and suggesting that EB200 induces functionally distinct T cell responses. The most efficient peptide for induction of proliferative responses was one previously shown to induce T cell responses in five different H-2 congenic mouse strains primed with EB200, suggesting that this is a universal T cell epitope. The presence of multiple B and T cell epitopes in EB200, widely recognized by humans, is important since EB200 has been shown to elicit protective antibody responses in monkeys and may be considered for inclusion in malaria subunit vaccines.The Plasmodium falciparum antigen Pf332 is of potential interest for inclusion in a subunit vaccine against the malaria parasite.

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Association between cellular response (IL‐4) to RESA/Pf155 and protection from clinical malaria among Papua New Guinean children living in a malaria endemic area

Cited by 22 publications

References 13 publications

Ex Vivo Interferon-Gamma Immune Response to Thrombospondin-Related Adhesive Protein in Coastal Kenyans: Longevity and Risk of Plasmodium Falciparum Infection

Ex Vivo Interferon-Gamma Immune Response to Thrombospondin-Related Adhesive Protein in Coastal Kenyans: Longevity and Risk of Plasmodium Falciparum Infection

Effects of ConcomitantSchistosoma haematobiumInfection on the Serum Cytokine Levels Elicited by AcutePlasmodium falciparumMalaria Infection in Malian Children

Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

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