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Abstract
ABSTRACTRecent 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.
Highlights
The most recent report by the World Health Organization indicates that in 2013 there were approximately 198 million malaria cases worldwide and an estimated 584,000 deaths [1]
In experiments to evaluate the protective effect of immune responses elicited by PfrCelTOS, we found that mice immunized with 20 g of PfrCelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvantliposome-QS21 (GLA-LSQ) adjuvant system had a significantly reduced parasite liver burden after challenge against chimeric PbANKA-PfCelTOS(r)PbCelTOSCelTOS parasites
In this study, we report the protective effect of functional immune responses and antibodies against the P. falciparum cell-traversal protein for ookinetes and sporozoites (CelTOS) protein
Summary
The most recent report by the World Health Organization indicates that in 2013 there were approximately 198 million malaria cases worldwide and an estimated 584,000 deaths [1]. RTS,S has shown potential to decrease the incidence of severe malaria in children and to prevent infection in 30 to 50% of its recipients [2,3,4] While these findings are encouraging, additional improvements may be required to accomplish a more broadly protective formulation. Besides CSP, a number of recent studies have explored the protective effect of immune responses targeting different sporozoite antigens [6,7,8,9] One of these antigens is the cell-traversal protein for ookinetes and sporozoites (CelTOS), which has a critical role in the establishment of malaria infections in both mosquito and vertebrate hosts [10]. Our results demonstrate that immune responses against CelTOS have the potential to inhibit Plasmodium infection and decrease malaria transmission
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