title: Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates.
abstract: OBJECTIVE
  Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria.
  
  
  METHODS
  We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45.
  
  
  RESULTS
  Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region.
  
  
  CONCLUSIONS
  We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity.
authors: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors: Sophie
authors: S
authors: Jones
authors: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors: Lynn
authors: L
authors: Grignard
authors: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.
authors: Issa
authors: I
authors: Nebie
authors: Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania.
authors: Jaffu
authors: J
authors: Chilongola
authors: Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana.
authors: Daniel
authors: D
authors: Dodoo
authors: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Robert
authors: R
authors: Sauerwein
authors: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Michael
authors: M
authors: Theisen
authors: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Will
authors: W
authors: Roeffen
authors: Gennova Bio Pharmaceuticals Limited, Pune, India.
authors: Shrawan Kumar
authors: SK
authors: Singh
authors: Gennova Bio Pharmaceuticals Limited, Pune, India.
authors: Rajesh Kumar
authors: RK
authors: Singh
authors: Gennova Bio Pharmaceuticals Limited, Pune, India.
authors: Sanjay
authors: S
authors: Singh
authors: Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana.
authors: Eric
authors: E
authors: Kyei-Baafour
authors: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors: Kevin
authors: K
authors: Tetteh
authors: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors: Chris
authors: C
authors: Drakeley
authors: Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: teun.bousema@lshtm.ac.uk.
authors: Teun
authors: T
authors: Bousema
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood*; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology*; D002050:Burkina Faso; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005869:Ghana; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013636:Tanzania
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; C430263:Pfs230 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; C084847:pfs48-45 protein, Plasmodium falciparum
keywords: Gamete; Gametocyte; Immunity; Plasmodium falciparum; Polymorphism; Transmission