STABILITY OF INTERFERON-γ AND INTERLEUKIN-10 RESPONSES TO PLASMODIUM FALCIPARUM LIVER STAGE ANTIGEN-1 AND THROMBOSPONDIN-RELATED ADHESIVE PROTEIN IN RESIDENTS OF A MALARIA HOLOENDEMIC AREA

ABSTRACT Gamma interferon (IFN-γ) responses to the Plasmodium falciparum antigens liver-stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) are thought to be important in protection against malaria. Optimal methods of testing and the effects of age and transmission intensity on these responses are unknown. IFN-γ responses to LSA-1 and TRAP peptides were assessed by the enzyme-linked immunospot assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA) in children and adults from areas of stable and unstable malaria transmission in Kenya. Adults in the areas of stable and unstable transmission had similar frequencies and levels of IFN-γ responses to LSA-1 and TRAP as determined by ELISPOT and ELISA. In contrast, IFN-γ responses to the LSA-1 T3 peptide (assessed by ELISPOT) and to any LSA-1 peptide (assessed by ELISA) were less frequent in children in the area of unstable transmission than in children in the area of stable transmission. IFN-γ responses to LSA-1 were more frequently detected by ELISA than by ELISPOT in the stable-transmission area. IFN-γ responses detected by ELISA and ELISPOT did not correlate with each other. In children in the stable-transmission area, IFN-γ responses to LSA-1 peptides assessed by ELISA, but not by ELISPOT, were associated with protection against clinical malaria and anemia. IFN-γ responses to LSA-1 appear to require repeated P. falciparum exposure and/or increased age and, as measured by ELISA, are associated with protection against clinical malaria and anemia.

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Antibodies to the Plasmodium falciparum Antigens Circumsporozoite Protein, Thrombospondin-Related Adhesive Protein, and Liver-Stage Antigen 1 Vary by Ages of Subjects and by Season in a Highland Area of Kenya

Infection and Immunity ◽

10.1128/iai.71.8.4320-4325.2003 ◽

2003 ◽

Vol 71 (8) ◽

pp. 4320-4325 ◽

Cited By ~ 39

Author(s):

Chandy C. John ◽

Joseph S. Zickafoose ◽

P. Odada Sumba ◽

Christopher L. King ◽

James W. Kazura

Keyword(s):

Plasmodium Falciparum ◽

Dry Season ◽

Circumsporozoite Protein ◽

Protective Effects ◽

Igg Antibodies ◽

Liver Stage ◽

Highland Area ◽

Adhesive Protein ◽

Adults And Children ◽

Dry Seasons

ABSTRACT Immunoglobulin G (IgG) antibodies to three vaccine candidate preerythrocytic Plasmodium falciparum antigens were evaluated in children and adults in an epidemic-prone highland area of Kenya during rainy (high-transmission) and dry (low-transmission) seasons. The frequencies and median levels of IgG antibodies to circumsporozoite protein (CSP) and thrombospondin-related adhesive protein (TRAP) were compared to the frequencies and median levels of IgG antibodies to liver-stage antigen 1 (LSA-1) reported previously. The frequencies and median levels of IgG antibodies to CSP and TRAP were similar in children and adults in the rainy season, but they were lower in children than in adults in the dry season. The frequencies and median levels of antibodies to LSA-1 were lower in children than in adults in both the rainy and dry seasons. Antibodies to CSP and LSA-1 were primarily members of the IgG1 and IgG3 subclasses, while antibodies to TRAP were primarily members of the IgG3 and IgG4 subclasses. In a treatment-reinfection study following dry season testing, antibodies to TRAP were associated with a trend toward protection from infection in children (P = 0.051) but not in adults. Antibodies to LSA-1 and CSP did not correlate with protection in children or adults. In this highland area of Kenya with unstable transmission, IgG antibodies to preerythrocytic P. falciparum antigens vary in subjects by age and season, and the protective effects of these antibodies against infection may be different in adults and children.

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Interferon-γ and Interleukin-10 Responses during Clinical Malaria Episodes in Infants Aged 0–2 Years Prenatally Exposed to Plasmodium falciparum: Tanzanian Birth Cohort

Journal of Tropical Medicine ◽

10.1155/2018/6847498 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Boniphace Sylvester ◽

Dinah B. Gasarasi ◽

Said Aboud ◽

Donath Tarimo ◽

Siriel Masawe ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Prenatal Exposure ◽

Geometric Mean ◽

Placental Malaria ◽

Clinical Malaria ◽

Interleukin 10 ◽

Interferon Γ ◽

Enzyme Linked Immunosorbent Assay ◽

Prenatally Exposed ◽

Malaria Episodes

Background. Infants born to mothers with placental malaria are prenatally exposed to Plasmodium falciparum antigens. However, the effect of that exposure to subsequent immune responses has not been fully elucidated. This study aimed at determining the effect of prenatal exposure to P. falciparum on Interleukin-10 and Interferon-γ responses during clinical malaria episodes in the first 24 months of life. Methods. This prospective cohort study involved 215 infants aged 0-2 years born to mothers with or without placental malaria. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of IL-10 and IFN-γ in infants and detect IgM in cord blood. Data were analyzed using SPSS version 20. Findings. Geometric mean for IFN-γ in exposed infants was 557.9 pg/ml (95% CI: 511.6-604.1) and in unexposed infants it was 634.4 pg/ml (95% CI: 618.2-668.5) (P=0.02). Mean IL-10 was 22.4 pg/ml (95% CI: 19.4-28.4) and 15.1 pg/ml (95%CI: 12.4-17.6), respectively (P=0.01). Conclusions. Prenatal exposure to P. falciparum antigens significantly affects IL-10 and IFN-γ responses during clinical malaria episodes in the first two years of life.

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The Plasmodium falciparum Antigen MB2 Induces Interferon-γ and Interleukin-10 Responses in Adults in Malaria Endemic Areas of Western Kenya

Journal of Global Infectious Diseases ◽

10.4103/0974-777x.122001 ◽

2013 ◽

Vol 5 (4) ◽

pp. 131 ◽

Cited By ~ 1

Author(s):

LyticiaA Ochola ◽

BartholomewN Ondigo ◽

GideonM Ng′wena ◽

GregoryS Noland ◽

George Ayodo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Interleukin 10 ◽

Interferon Γ ◽

Western Kenya ◽

Endemic Areas

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Faculty Opinions recommendation of Antibodies to the Plasmodium falciparum antigens circumsporozoite protein, thrombospondin-related adhesive protein, and liver-stage antigen 1 vary by ages of subjects and by season in a highland area of Kenya.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.719352138.793500854 ◽

2014 ◽

Author(s):

James Beeson

Keyword(s):

Plasmodium Falciparum ◽

Circumsporozoite Protein ◽

Liver Stage ◽

Highland Area ◽

Adhesive Protein

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Interleukin-10 Responses to Liver-Stage Antigen 1 Predict Human Resistance to Plasmodium falciparum

Infection and Immunity ◽

10.1128/iai.67.7.3424-3429.1999 ◽

1999 ◽

Vol 67 (7) ◽

pp. 3424-3429 ◽

Cited By ~ 45

Author(s):

Jonathan D. Kurtis ◽

David E. Lanar ◽

Malachi Opollo ◽

Patrick E. Duffy

Keyword(s):

Plasmodium Falciparum ◽

Immune Responses ◽

Eradication Therapy ◽

Therapy Resistance ◽

Interleukin 10 ◽

Effective Vaccine ◽

Necrosis Factor Alpha ◽

Liver Stage ◽

Humoral Immune ◽

Humoral Immune Responses

ABSTRACT The design of an effective vaccine against Plasmodium falciparum, the most deadly malaria parasite of humans, requires a careful definition of the epitopes and the immune responses involved in protection. Liver-stage antigen 1 (LSA-1) is specifically expressed during the hepatic stage of P. falciparum and elicits cellular and humoral immune responses in naturally exposed individuals. We report here that interleukin-10 (IL-10) production in response to LSA-1 predicts resistance to P. falciparum after eradication therapy. Resistance was not related to gamma interferon or tumor necrosis factor alpha production. This is the first report that human IL-10 responses are associated with resistance after eradication therapy, and our findings support the inclusion of LSA-1 in a vaccine against malaria.

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Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis

Malaria Journal ◽

10.1186/s12936-021-03664-8 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Li-Yun Lin ◽

Hui-Ying Huang ◽

Xue-Yan Liang ◽

Dong-De Xie ◽

Jiang-Tao Chen ◽

...

Keyword(s):

Genetic Diversity ◽

Plasmodium Falciparum ◽

Natural Selection ◽

Protein Structure ◽

Transmembrane Protein ◽

Fixation Index ◽

Bioko Island ◽

Adhesive Protein ◽

Trap Gene ◽

Selection Of

Abstract Background Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. Methods 153 blood spot samples from Bioko malaria patients were collected during 2016–2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. Results A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN–dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. Conclusions Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

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