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

<h4>Background</h4>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 Plasm...

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Autores principales: Elke S Bergmann-Leitner, Ryan M Mease, Patricia De La Vega, Tatyana Savranskaya, Mark Polhemus, Christian Ockenhouse, Evelina Angov
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:657518e76283467787c73792401c17052021-11-18T06:35:52ZImmunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.1932-620310.1371/journal.pone.0012294https://doaj.org/article/657518e76283467787c73792401c17052010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20808868/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Elke S Bergmann-LeitnerRyan M MeasePatricia De La VegaTatyana SavranskayaMark PolhemusChristian OckenhouseEvelina AngovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12294 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elke S Bergmann-Leitner
Ryan M Mease
Patricia De La Vega
Tatyana Savranskaya
Mark Polhemus
Christian Ockenhouse
Evelina Angov
Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format article
author Elke S Bergmann-Leitner
Ryan M Mease
Patricia De La Vega
Tatyana Savranskaya
Mark Polhemus
Christian Ockenhouse
Evelina Angov
author_facet Elke S Bergmann-Leitner
Ryan M Mease
Patricia De La Vega
Tatyana Savranskaya
Mark Polhemus
Christian Ockenhouse
Evelina Angov
author_sort Elke S Bergmann-Leitner
title Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
title_short Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
title_full Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
title_fullStr Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
title_full_unstemmed Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
title_sort immunization with pre-erythrocytic antigen celtos from plasmodium falciparum elicits cross-species protection against heterologous challenge with plasmodium berghei.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/657518e76283467787c73792401c1705
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