title: Naturally acquired immunity to sexual stage P. falciparum parasites.
abstract: Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.
authors.affiliation: Department of Medical Microbiology,Radboud University Medical Center,Geert-Grooteplein 28,6525 GA Nijmegen,The Netherlands.
authors.forename: Will J R
authors.initials: WJ
authors.lastname: Stone
authors.affiliation: Department of Immunology and Infectious Diseases,Harvard School of Public Health,Boston,Massachusetts 02115,USA.
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Dantzler
authors.affiliation: Department of Immunology and Infectious Diseases,Harvard School of Public Health,Boston,Massachusetts 02115,USA.
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Nilsson
authors.affiliation: Department of Immunology & Infection,Faculty of Infectious and Tropical Diseases,London School of Hygiene and Tropical Medicine,London, WC1E 7HT,United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.affiliation: Department of Immunology and Infectious Diseases,Harvard School of Public Health,Boston,Massachusetts 02115,USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Marti
authors.affiliation: Department of Medical Microbiology,Radboud University Medical Center,Geert-Grooteplein 28,6525 GA Nijmegen,The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
authors.affiliation: Department of Medical Microbiology,Radboud University Medical Center,Geert-Grooteplein 28,6525 GA Nijmegen,The Netherlands.
authors.forename: Sanna R
authors.initials: SR
authors.lastname: Rijpma
mesh_terms: D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008018:Life Cycle Stages / Q000276:immunology*; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology* / Q000635:transmission; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines
keywords: Plasmodium falciparum; gametes; gametocytes; immunity; malaria; transmission