Sophie Jones1, Lynn Grignard1, Issa Nebie2, Jaffu Chilongola3, Daniel Dodoo4, Robert Sauerwein5, Michael Theisen6, Will Roeffen5, Shrawan Kumar Singh7, Rajesh Kumar Singh7, Sanjay Singh7, Eric Kyei-Baafour4, Kevin Tetteh1, Chris Drakeley1, Teun Bousema8. 1. Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom. 2. Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. 3. Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania. 4. Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana. 5. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. 6. 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. 7. Gennova Bio Pharmaceuticals Limited, Pune, India. 8. 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.
Abstract
OBJECTIVES: 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.
OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparumsexual 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.
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