title: Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites.
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.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA. ann.moormann@umassmed.edu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moormann
authors.forename: Peter Odada
authors.initials: PO
authors.lastname: Sumba
authors.forename: Kiprotich
authors.initials: K
authors.lastname: Chelimo
authors.forename: Hua
authors.initials: H
authors.lastname: Fang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tisch
authors.forename: Arlene E
authors.initials: AE
authors.lastname: Dent
authors.forename: Chandy C
authors.initials: CC
authors.lastname: John
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: John
authors.initials: J
authors.lastname: Vulule
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006451:Hemoglobin, Sickle / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D055815:Young Adult
chemical_list: D006451:Hemoglobin, Sickle; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Merozoite Surface Protein 1; cellular immunity; human immunity; humoral immunity; interferon-gamma; interleukin-10; longitudinal study; observational study; sickle cell trait
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