Publication: Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from <i>Plasmodium</i> Challenge in a Mouse Model.
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Date
2020-01-10T00:00:00Z
Authors
Authors
Reeder, SM
Reuschel, EL
Bah, MA
Yun, K
Tursi, NJ
Kim, KY
Chu, J
Zaidi, FI
Yilmaz, I
Hart, RJ
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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.
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Citation
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 <i>Plasmodium</i> Challenge in a Mouse Model.-, Vaccines, cilt.8, 2020