Accession Number : ADA531954


Title :   Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei


Descriptive Note : Journal article


Corporate Author : WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD


Personal Author(s) : Bergmann-Leitner, Elke S. ; Mease, Ryan M. ; LaVega, Patricia D. ; Savranskaya, Tatyana ; Polhemus, Mark ; Ockenhouse, Christian ; Angov, Evelina


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA531954


Report Date : AUG 2010


Pagination or Media Count : 10


Abstract : 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. Methodology/Principal Findings: 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/Significance: 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.


Descriptors :   *PLASMODIUM BERGHEI , *MALARIA , *SPOROZOITES , *VACCINES , *PLASMODIUM FALCIPARUM , IN VIVO ANALYSIS , ERYTHROCYTES , CELLS(BIOLOGY) , ANTIGENS , IMMUNIZATION , HOSTS(BIOLOGY) , STERILIZATION , CULICIDAE , IMMUNITY , INFECTIOUS DISEASES , RESPONSE(BIOLOGY) , VERTEBRATES , IN VITRO ANALYSIS , ESCHERICHIA COLI


Subject Categories : MEDICINE AND MEDICAL RESEARCH
      MICROBIOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE