title: Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children.
abstract: Immunity to the sexual stages of Plasmodium falciparum can be induced during natural infections. Characterization of this immunity may facilitate the design of a transmission-blocking vaccine (TBV). This study aimed to assess the prevalence and serological correlates of functional transmission-blocking immunity in Gambian children (aged 1-4 years old) who were P. falciparum gametocyte carriers. Serological assays showed 100% response to fixed, whole parasites but only 42% to live gametes. Responses to the antigens Pfs230 and Pfs48/45 were 54.1% and 37.3%, respectively, in an IgG1 ELISA. 14/55 sera were capable of reducing the infectivity of laboratory isolate NF54 in a standard membrane-feeding assay (SMFA). This activity was strongly correlated with IgG1 responses to Pfs48/45 (r = 0.49, P < 0.001) and to a serological reaction with epitopes of the same molecule (r = 0.38, P = 0.003). A weaker correlation was observed with IgG1 to Pfs230 (r = 0.29, P = 0.03). In direct membrane feeding assays (DMFA) with autologous isolates, sera from 4/29 children showed transmission-blocking activity. There was no correlation with serological assays and the DMFA or between the SMFA and DMFA. This may be caused by variation in sexual stage antigens and/or alternative modes of transmission-blocking immunity, both of which have implications for vaccine implementation.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel St., London WC1E 7HT, UK. chris.drakeley@lshtm.ac.uk
authors.forename: C J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: W
authors.initials: W
authors.lastname: Eling
authors.forename: K
authors.initials: K
authors.lastname: Teelen
authors.forename: J T
authors.initials: JT
authors.lastname: Bousema
authors.forename: R
authors.initials: R
authors.lastname: Sauerwein
authors.forename: B M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: G A T
authors.initials: GA
authors.lastname: Targett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology; D002353:Carrier State / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D002675:Child, Preschool; D009033:Culicidae / Q000469:parasitology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D010455:Peptides