title: Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens.
abstract: Cytophilic immunoglobulin (IgG) subclass responses (IgG1 and IgG3) to Plasmodium falciparum antigens have been associated with protection from malaria, yet the relative importance of transmission intensity and age in generation of subclass responses to pre-erythrocytic and blood-stage antigens have not been clearly defined. We analyzed IgG subclass responses to the pre-erythrocytic antigens CSP, LSA-1, and TRAP and the blood-stage antigens AMA-1, EBA-175, and MSP-1 in asymptomatic residents age 2 years or older in stable (n=116) and unstable (n=96) transmission areas in Western Kenya. In the area of stable malaria transmission, a high prevalence of cytophilic (IgG1 and IgG3) antibodies to each antigen was seen in all age groups. Prevalence and levels of cytophilic antibodies to pre-erythrocytic and blood-stage P. falciparum antigens increased with age in the unstable transmission area, yet IgG1 and IgG3 responses to most antigens for all ages in the unstable transmission area were less prevalent and lower in magnitude than even the youngest age group from the stable transmission area. The dominance of cytophilic responses over non-cytophilic (IgG2 and IgG4) was more pronounced in the stable transmission area, and the ratio of IgG3 over IgG1 generally increased with age. In the unstable transmission area, the ratio of cytophilic to non-cytophilic antibodies did not increase with age, and tended to be IgG3-biased for pre-erythrocytic antigens yet IgG1-biased for blood-stage antigens. The differences between areas could not be attributed to active parasitemia status, as there were minimal differences in antibody responses between those positive and negative for Plasmodium infection by microscopy in the stable transmission area. Individuals in areas of unstable transmission have low cytophilic to non-cytophilic IgG subclass ratios and low IgG3:IgG1 ratios to P. falciparum antigens. These imbalances could contribute to the persistent risk of clinical malaria in these areas and serve as population-level, age-specific biomarkers of transmission.
authors.affiliation: Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, 717 Delaware Street, SE, Room 363, Minneapolis, MN 55414, USA. Electronic address: gregory.noland@emory.edu.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Noland
authors.affiliation: Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, 717 Delaware Street, SE, Room 363, Minneapolis, MN 55414, USA. Electronic address: jansenpa@gmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Jansen
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. Electronic address: vulule@yahoo.com.
authors.forename: John M
authors.initials: JM
authors.lastname: Vulule
authors.affiliation: Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, 717 Delaware Street, SE, Room 363, Minneapolis, MN 55414, USA. Electronic address: parkx479@umn.edu.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Park
authors.affiliation: Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. Electronic address: ondigo2002@yahoo.com.
authors.forename: Bartholomew N
authors.initials: BN
authors.lastname: Ondigo
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, 10900 Euclid Avenue LC: 7286, Cleveland, OH 44106, USA. Electronic address: james.kazura@case.edu.
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
authors.affiliation: Division of Pediatric Immunology & Infectious Diseases, Department of Pediatrics, University of Massachusetts Medical School - Biotech II, 373 Plantation Street, Suite 318, Worcester, MA 01605, USA. Electronic address: ann.moormann@umassmed.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Moormann
authors.affiliation: Division of Global Pediatrics, Department of Pediatrics, University of Minnesota Medical School, 717 Delaware Street, SE, Room 363, Minneapolis, MN 55414, USA. Electronic address: ccj@umn.edu.
authors.forename: Chandy C
authors.initials: CC
authors.lastname: John
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015995:Prevalence; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G
keywords: Antibodies; Blood-stage antigen; Immunity; Malaria; Pre-erythrocytic antigen; Subclass