title: Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
abstract: BACKGROUND
  The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium.
  
  
  RESULTS
  To test this hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS protein that can be produced to high yields in the E. coli expression system. Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the recombinant protein adjuvanted with Montanide ISA 720 and characterized using in vitro and in vivo analyses.
  
  
  CONCLUSIONS
  Immunization with PfCelTOS resulted in potent humoral and cellular immune responses and most importantly induced sterile protection against a heterologous challenge with P. berghei sporozoites in a proportion of both inbred and outbred mice. The biological activity of CelTOS-specific antibodies against the malaria parasite is likely linked to the impairment of sporozoite motility and hepatocyte infectivity. The results underscore the potential of this antigen as a pre-erythrocytic vaccine candidate and demonstrate for the first time a malaria vaccine that is cross-protective between species.
authors.affiliation: Division of Malaria Vaccine Development, United States Military Malaria Vaccine Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Elke S
authors.initials: ES
authors.lastname: Bergmann-Leitner
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Mease
authors.forename: Patricia
authors.initials: P
authors.lastname: De La Vega
authors.forename: Tatyana
authors.initials: T
authors.lastname: Savranskaya
authors.forename: Mark
authors.initials: M
authors.lastname: Polhemus
authors.forename: Christian
authors.initials: C
authors.lastname: Ockenhouse
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D004912:Erythrocytes; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D007114:Immunization / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008353:Mannitol / Q000031:analogs & derivatives; D051379:Mice; D009068:Movement; D009829:Oleic Acids; D010962:Plasmodium berghei / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000502:physiology; D012995:Solubility; D034101:Sporozoites / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D009829:Oleic Acids; D015847:Interleukin-4; C001681:mannide monooleate; D008353:Mannitol; D007371:Interferon-gamma
references.citation: Malar J. 2010 May 27;9:145
references.pmid: 20507620
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9952-7
references.pmid: 12886016
references.citation: J Vector Borne Dis. 2008 Mar;45(1):1-20
references.pmid: 18399312
references.citation: Int Immunol. 2005 Mar;17(3):245-55
references.pmid: 15710912
references.citation: Clin Exp Immunol. 1974 Jun;17(2):329-38
references.pmid: 4469223
references.citation: Mol Microbiol. 2004 Mar;51(5):1221-32
references.pmid: 14982620
references.citation: J Infect Dis. 2009 Aug 1;200(3):329-36
references.pmid: 19569964
references.citation: Exp Parasitol. 1993 Sep;77(2):129-35
references.pmid: 8375482
references.citation: Mol Microbiol. 2006 Mar;59(5):1369-79
references.pmid: 16468982
references.citation: J Protozool. 1988 Aug;35(3):389-93
references.pmid: 3054075
references.citation: J Immunol. 1976 Mar;116(3):859-67
references.pmid: 815435
references.citation: Lancet. 2004 Oct 16-22;364(9443):1411-20
references.pmid: 15488216
references.citation: Nature. 1969 May 3;222(5192):488-9
references.pmid: 5768632
references.citation: Infect Immun. 2000 Oct;68(10):5914-9
references.pmid: 10992502
references.citation: J Parasitol. 1984 Oct;70(5):831-3
references.pmid: 6150971
references.citation: PLoS One. 2008 May 14;3(5):e2189
references.pmid: 18478103
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9781-6
references.pmid: 10449771
references.citation: Eur J Immunol. 2001 Mar;31(3):692-8
references.pmid: 11241272
references.citation: Infect Immun. 2005 Jan;73(1):287-97
references.pmid: 15618165
references.citation: J Immunol. 1997 Dec 15;159(12):6112-9
references.pmid: 9550412
references.citation: Biotechniques. 1996 May;20(5):797-800
references.pmid: 8723921
references.citation: Parasite Immunol. 2009 Sep;31(9):560-73
references.pmid: 19691559