1. Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Plasmodium Challenge in a Mouse Model
- Author
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Reeder, SM, Reuschel, EL, Bah, MA, Yun, K, Tursi, NJ, Kim, KY, Chu, J, Zaidi, FI, Yilmaz, I, Hart, RJ, Perrin, B, Xu, Z, Humeau, L, Weiner, DB, Aly, Ahmed Sayed Ibrahım, and ALY, Ahmed Sayed Ibrahım
- Subjects
parasitic diseases ,Reeder S., Reuschel E., Bah M., Yun K., Tursi N., Kim K., Chu J., Zaidi F., Yilmaz I., Hart R., et al., -Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Plasmodium Challenge in a Mouse Model.-, Vaccines, cilt.8, 2020 - Abstract
The need for a malaria vaccine is indisputable. A single vaccine for Plasmodium pre-erythrocytic stages targeting the major sporozoite antigen circumsporozoite protein (CSP) has had partial success. Additionally, CD8+ T cells targeting liver-stage (LS) antigens induced by live attenuated sporozoite vaccines were associated with protection in human challenge experiments. To further evaluate protection mediated by LS antigens, we focused on exported pre-erythrocytic proteins (exported protein 1 (EXP1), profilin (PFN), exported protein 2 (EXP2), inhibitor of cysteine proteases (ICP), transmembrane protein 21 (TMP21), and upregulated in infective sporozoites-3 (UIS3)) expressed in all Plasmodium species and designed optimized, synthetic DNA (synDNA) immunogens. SynDNA antigen cocktails were tested with and without the molecular adjuvant plasmid IL-33. Immunized animals developed robust T cell responses including induction of antigen-specific liver-localized CD8+ T cells, which were enhanced by the co-delivery of plasmid IL-33. In total, 100% of mice in adjuvanted groups and 71%–88% in non-adjuvanted groups were protected from blood-stage disease following Plasmodium yoelii sporozoite challenge. This study supports the potential of synDNA LS antigens as vaccine components for malaria parasite infection. Türkiye Bilimsel Ve Teknolojik Araştırma Kurumu ( Tubitak )
- Published
- 2020