Immunogenicity, protective efficacy and safety of a recombinant DNA vaccine encoding truncated Plasmodium yoelii sporozoite asparagine-rich protein 1 (PySAP1)

编码截短型约氏疟原虫子孢子富含天冬酰胺蛋白 1(PySAP1)的重组 DNA 疫苗的免疫原性、保护效力和安全性

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作者:Jia Zhao, Shu Deng, Jiayuan Liang, Yaming Cao, Jun Liu, Feng Du, Hong Shang, Liwang Cui, Enjie Luo

Abstract

Although great efforts have been undertaken for the development of malaria vaccines, no completely effective malaria vaccines are available yet. Despite being clinically silent, the pre-erythrocytic stage is considered an ideal target for the development of malaria vaccines. Sporozoite asparagine-rich protein 1 (SAP1) is a sporozoite-localized protein that regulates the expression of UIS (upregulated in infectious sporozoites) genes, which are essential for the infectivity of sporozoites. In this study, a recombinant DNA vaccine encoding a predicted antigenic determinant region of Plasmodium yoelii SAP1 (PySAP1) was constructed. Immunization of mice with this DNA vaccine construct resulted in significant elevation of cytokines such as IFN-γ, IL-2, IL-4 and IL-10, and total IgG as compared with control groups immunized with either the empty DNA vector or saline. After challenge with sporozoites, the group receiving the DNA vaccine showed delayed development of parasitemia and prolonged survival time compared with the control group. The DNA vaccine provided partial protection against P. yoelii 17XL infection, with an overall protection rate of 20%. In addition, the DNA vaccine did not show integration into the host genome. Further studies of SAP1 are needed to test whether it can be used as subunit vaccine candidate.

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