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Abstract
BackgroundA malaria vaccine that targets the sporozoite/liver stage parasites could potentially prevent blood stage infection and the associated clinical symptoms. Identification of sporozoite/liver stage antigens is, therefore, crucial for the development of effective vaccines. Cell-traversal protein for ookinetes and sporozoites (CelTOS) is a highly conserved antigen involved in sporozoite motility and hepatocyte invasion and has been shown to induce significant IFN-γ production in PBMCs from radiation-attenuated sporozoite-immunized malaria-naïve individuals. The aim of this study was to ascertain whether such CelTOS-specific recall responses are also induced in individuals with natural exposure to Plasmodium falciparum.MethodsEx vivo IFN-γ responses to 15mer overlapping peptide pools covering the entire sequence of CelTOS and five other candidate antigens, CSP, AMA1, MSP1, TRAP and LSA1, were characterized using PBMCs from 35 malaria exposed adults. Responses to four CelTOS peptide pools (CelTp1, CelTp2, CelTp3 and CelTp4), a pool containing peptides from the entire CelTOS antigen (CelTTp), and pools comprised of overlapping peptides from each of the other five malaria antigens were assessed by ex vivo ELISpot assay. A positive IFN-γ response for stimulants was defined by two criteria; a stimulation index of two or greater relative to the unstimulated control, and a difference of 10 or greater in spot forming cells between stimulant and the unstimulated control.ResultsOf the 35 volunteers tested, five had positive IFN-γ recall responses against the four different CelTOS pools while four volunteers made responses against the CelTTp pool; six volunteers were, therefore, positive with CelTOS. By contrast, six volunteers responded to AMA1, seven to LSA1, 15 to MSP1 and two volunteers responded against CSP and TRAP.ConclusionsThese results suggest natural malaria transmission induces CelTOS-specific ex vivo IFN-γ in Ghanaian adults and that the frequency of these responses was similar to those of other previously characterized malaria antigens. These findings support the further evaluation of CelTOS as a pre-erythrocytic candidate antigen for inclusion in a potential multi-antigen vaccine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-014-0539-5) contains supplementary material, which is available to authorized users.
Highlights
A malaria vaccine that targets the sporozoite/liver stage parasites could potentially prevent blood stage infection and the associated clinical symptoms
The results showed that with the exception of merozoite surface protein-1 (MSP1), Cell-traversal protein for ookinetes and sporozoites (CelTOS) peptides recalled a similar frequency of positive responses as the other four antigens, suggesting that CelTOS may be a potentially important antigen for inclusion in a multi-antigen malaria vaccine
All female volunteers tested negative for pregnancy and all volunteers were negative for malaria parasitaemia by light microscopy and malaria rapid diagnostic test (RDT)
Summary
A malaria vaccine that targets the sporozoite/liver stage parasites could potentially prevent blood stage infection and the associated clinical symptoms. Various insecticides have been applied for the control of the mosquito vectors, and chemoprophylaxis is used to prevent blood stage infection associated with the clinical symptoms of malaria. These disease control measures are being hampered by the resistance of parasites and mosquito vectors to drugs and insecticides respectively [1]. The feasibility of developing a malaria vaccine is firstly suggested by the acquisition of partial clinical immunity following repeated exposure to parasites during natural transmission in malaria-endemic areas [2,3]. Immunization with radiation-attenuated sporozoites has been shown to induce sterile protection against the sporozoite and liver stages of the parasite [4,5]
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