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

Reeder, Sophia M.; Reuschel, Emma L.; Bah, Mamadou A.; Yun, Kun; Tursi, Nicholas J.; Kim, Kevin Y.; Chu, Jacqueline; Zaidi, Faraz, I; Yilmaz, Ilknur; Hart, Robert J.; Perrin, Benjamin; Xu, Ziyang; Humeau, Laurent; Weiner, David B.; Aly, Ahmed S., I


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{
  "DOI": "10.3390/vaccines8010021", 
  "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.", 
  "author": [
    {
      "family": "Reeder", 
      "given": " Sophia M."
    }, 
    {
      "family": "Reuschel", 
      "given": " Emma L."
    }, 
    {
      "family": "Bah", 
      "given": " Mamadou A."
    }, 
    {
      "family": "Yun", 
      "given": " Kun"
    }, 
    {
      "family": "Tursi", 
      "given": " Nicholas J."
    }, 
    {
      "family": "Kim", 
      "given": " Kevin Y."
    }, 
    {
      "family": "Chu", 
      "given": " Jacqueline"
    }, 
    {
      "family": "Zaidi", 
      "given": " Faraz"
    }, 
    {
      "family": "Yilmaz", 
      "given": " Ilknur"
    }, 
    {
      "family": "Hart", 
      "given": " Robert J."
    }, 
    {
      "family": "Perrin", 
      "given": " Benjamin"
    }, 
    {
      "family": "Xu", 
      "given": " Ziyang"
    }, 
    {
      "family": "Humeau", 
      "given": " Laurent"
    }, 
    {
      "family": "Weiner", 
      "given": " David B."
    }, 
    {
      "family": "Aly", 
      "given": " Ahmed S."
    }
  ], 
  "container_title": "VACCINES", 
  "id": "10305", 
  "issue": "1", 
  "issued": {
    "date-parts": [
      [
        2020, 
        1, 
        1
      ]
    ]
  }, 
  "title": "Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from Plasmodium Challenge in a Mouse Model", 
  "type": "article-journal", 
  "volume": "8"
}
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