Humoral and cellular immunity to plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites

Ann M. Moormann, Peter Odada Sumba, Kiprotich Chelimo, Hua Fang, Daniel J. Tisch, Arlene E. Dent, Chandy John, Carole A. Long, John Vulule, James W. Kazura

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.Methods. The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.Results. Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.Conclusions. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalJournal of Infectious Diseases
Volume208
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Fingerprint

Merozoite Surface Protein 1
Plasmodium falciparum
Humoral Immunity
Cellular Immunity
Interferons
Parasites
Interleukin-10
Malaria
Infection
Parasitemia
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Alleles
Sickle Hemoglobin
Antibodies
Kenya
Adaptive Immunity
Proportional Hazards Models
Antibody Formation
Vaccines

Keywords

  • cellular immunity
  • human immunity
  • humoral immunity
  • interferon-gamma
  • interleukin-10
  • longitudinal study
  • Merozoite Surface Protein 1
  • observational study
  • sickle cell trait

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Humoral and cellular immunity to plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites. / Moormann, Ann M.; Sumba, Peter Odada; Chelimo, Kiprotich; Fang, Hua; Tisch, Daniel J.; Dent, Arlene E.; John, Chandy; Long, Carole A.; Vulule, John; Kazura, James W.

In: Journal of Infectious Diseases, Vol. 208, No. 1, 01.07.2013, p. 149-158.

Research output: Contribution to journalArticle

Moormann, Ann M. ; Sumba, Peter Odada ; Chelimo, Kiprotich ; Fang, Hua ; Tisch, Daniel J. ; Dent, Arlene E. ; John, Chandy ; Long, Carole A. ; Vulule, John ; Kazura, James W. / Humoral and cellular immunity to plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites. In: Journal of Infectious Diseases. 2013 ; Vol. 208, No. 1. pp. 149-158.
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abstract = "Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.Methods. The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.Results. Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.Conclusions. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.",
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T1 - Humoral and cellular immunity to plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites

AU - Moormann, Ann M.

AU - Sumba, Peter Odada

AU - Chelimo, Kiprotich

AU - Fang, Hua

AU - Tisch, Daniel J.

AU - Dent, Arlene E.

AU - John, Chandy

AU - Long, Carole A.

AU - Vulule, John

AU - Kazura, James W.

PY - 2013/7/1

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N2 - Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.Methods. The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.Results. Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.Conclusions. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.

AB - Background. Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.Methods. The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.Results. Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.Conclusions. Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.

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KW - interleukin-10

KW - longitudinal study

KW - Merozoite Surface Protein 1

KW - observational study

KW - sickle cell trait

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DO - 10.1093/infdis/jit134

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