Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world. Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans. Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery. In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria. Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
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http://dx.doi.org/10.1007/s12033-018-0140-1 | DOI Listing |
Front Immunol
January 2023
Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
The secreted malarial protein, Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS), is highly conserved among species, and plays a role in the invasion of mosquito midgut cells and hepatocytes in the vertebrate host. CelTOS was identified as a potential protective antigen based on a proteomic analysis, which showed that CelTOS stimulated significant effector T cells producing IFN-γ in peripheral blood mononuclear cells (PBMCs) from radiation attenuated sporozoite-immunized, malaria-naïve human subjects. In a rodent malaria model, recombinant full-length CelTOS protein/adjuvant combinations induced sterile protection, and in several studies, functional antibodies were produced that had hepatocyte invasion inhibition and transmission-blocking activities.
View Article and Find Full Text PDFVaccine
July 2022
Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. Electronic address:
Despite the development of prophylactic anti-malarial drugs and practices to prevent infection, malaria remains a health concern. Preclinical testing of novel malaria vaccine strategies achieved through rational antigen selection and novel particle-based delivery platforms is yielding encouraging results. One such platform, self-assembling virus-like particles (VLP) is safer than attenuated live viruses, and has been approved as a vaccination tool by the FDA.
View Article and Find Full Text PDFAMB Express
October 2019
Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.
Codon usage frequency influences protein structure and function. The frequency with which codons are used potentially impacts primary, secondary and tertiary protein structure. Poor expression, loss of function, insolubility, or truncation can result from species-specific differences in codon usage.
View Article and Find Full Text PDFMalar J
April 2019
Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Pasteur Avenue, P.O. Box 1316943551, Tehran, Iran.
Background: Plasmodium falciparum parasite is the most deadly species of human malaria, and the development of an effective vaccine that prevents P. falciparum infection and transmission is a key target for malarial elimination and eradication programmes. P.
View Article and Find Full Text PDFInfect Immun
June 2019
Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
cell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an advanced vaccine candidate that has a crucial role in the traversal of the malaria parasite in both mosquito and mammalian hosts. As recombinant purified proteins are normally poor immunogens, they require to be admixed with an adjuvant(s); therefore, the objective of the present study was to evaluate the capacity of different vaccine adjuvants, monophosphoryl lipid A (MPL), CpG, and Molina fraction 21 (QS-21), alone or in combination (MCQ [MPL/CpG/QS-21]), to enhance the immunogenicity of -expressed PfCelTOS in BALB/c mice. This goal was achieved by the assessment of anti-PfCelTOS IgG antibodies (level, titer, IgG isotype profile, avidity, and persistence) and extracellular Th1 cytokines using an enzyme-linked immunosorbent assay (ELISA) on postimmunized BALB/c mouse sera and PfCelTOS-stimulated splenocytes, respectively.
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