Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Plasmodium Challenge in a Mouse Model

Vaccines

Ilknur Yilmaz¹  AhmedS. I. Aly¹  RobertJ. Hart²  Benjamin Perrin²  Laurent Humeau³  FarazI. Zaidi⁴  Jacqueline Chu⁴  DavidB. Weiner⁴  SophiaM. Reeder⁴  EmmaL. Reuschel⁴  KevinY. Kim⁴  Kun Yun⁴  MamadouA. Bah⁴  NicholasJ. Tursi⁴  Ziyang Xu⁴ 

[1] Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34820, Turkey;Department of Tropical Medicine, Tulane University, New Orleans, LA 70112, USA;Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA;The Vaccine Center, Wistar Institute, Philadelphia, PA 19104, USA;

关键词: malaria;    plasmodium;    liver stage;    exported proteins;    dna vaccines;   

DOI  :  10.3390/vaccines8010021

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown