Person: ALY, AHMED SAYED IBRAHıM
Loading...
Status
Kurumdan Ayrılmıştır
Organizational Units
1 results
Search Results
Now showing 1 - 1 of 1
Publication Open Access Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from <i>Plasmodium</i> Challenge in a Mouse Model.(2020-01-10T00:00:00Z) 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; ALY, AHMED SAYED IBRAHıMThe 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.