Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei

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 im...

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Bibliographic Details
Published in:PloS one 2010-08, Vol.5 (8), p.e12294-e12294
Main Authors: Bergmann-Leitner, Elke S, Mease, Ryan M, De La Vega, Patricia, Savranskaya, Tatyana, Polhemus, Mark, Ockenhouse, Christian, Angov, Evelina
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Analysis
Animals
Antibodies
Antibodies, Monoclonal - immunology
Antibody Specificity
Antigens
Antigens, Protozoan - chemistry
Antigens, Protozoan - genetics
Antigens, Protozoan - immunology
Aquatic insects
Biological activity
Biological effects
Codons
Cross Reactions
Culicidae
Deoxyribonucleic acid
DNA
E coli
Erythrocytes
Escherichia coli
Escherichia coli - genetics
Female
Health aspects
Hepatocytes - parasitology
Humans
Immune response
Immune response (cell-mediated)
Immune response (humoral)
Immune system
Immunization
Immunization - methods
Immunology
Immunology/Immune Response
Immunology/Immunity to Infections
In vivo methods and tests
Inbreeding
Infection
Infections
Infectious Diseases/Tropical and Travel-Associated Diseases
Infectivity
Interferon-gamma - biosynthesis
Interleukin-4 - biosynthesis
Liver
Malaria
Malaria vaccines
Mannitol - analogs & derivatives
Mice
Microbiology/Parasitology
Movement
Oleic Acids
Parasites
Plasmodium
Plasmodium berghei
Plasmodium berghei - immunology
Plasmodium falciparum
Plasmodium falciparum - immunology
Plasmodium falciparum - physiology
Protected species
Proteins
Recombinant proteins
Solubility
Species
Sporozoites
Sporozoites - immunology
Sporozoites - metabolism
T cell receptors
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Vaccines
Vector-borne diseases
Vertebrates
Wildlife conservation
Zygotes
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Summary: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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012294