title: The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines.
abstract: Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal antibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses elicited by vaccination or passive immunization can inhibit sporozoite and ookinete infection and impair vector transmission.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Espinosa
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Vega-Rodriguez
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Yevel
authors.initials: Y
authors.lastname: Flores-Garcia
authors.affiliation: Leidos Life Sciences, Frederick, Maryland, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Noe
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Pfenex Inc., San Diego, California, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Coleman
authors.affiliation: Pfenex Inc., San Diego, California, USA.
authors.forename: Torben
authors.initials: T
authors.lastname: Bruck
authors.affiliation: Pfenex Inc., San Diego, California, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Haney
authors.affiliation: Pfenex Inc., San Diego, California, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Stevens
authors.affiliation: Pfenex Inc., San Diego, California, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Retallack
authors.affiliation: Pfenex Inc., San Diego, California, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Allen
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Vedvick
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Fox
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Randall F
authors.initials: RF
authors.lastname: Howard
authors.affiliation: The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.|Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Salman
authors.affiliation: Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.affiliation: Leiden Malaria Research Group, Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA fzavala1@jhu.edu gabriel.m.gutierrez@leidos.com.
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
authors.affiliation: Leidos Life Sciences, Frederick, Maryland, USA fzavala1@jhu.edu gabriel.m.gutierrez@leidos.com.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Gutierrez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000187:drug effects / Q000469:parasitology; D007114:Immunization; D007116:Immunization, Passive; D008018:Life Cycle Stages; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology* / Q000517:prevention & control / Q000635:transmission; D051379:Mice; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins; D034101:Sporozoites / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins
keywords: CelTOS; malaria; parasite; transgenic; vaccine