Synthetic Dna Vaccines Adjuvanted With Pil-33 Drive Liver-Localized T Cells And Provide Protection From Plasmodium Challenge In A Mouse Model
| Autor: | Emma L. Reuschel, Kevin Kim, Robert J. Hart, David B. Weiner, Sophia M. Reeder, Kun Yun, Ahmed S. I. Aly, Ziyang Xu, Laurent Humeau, Nicholas J. Tursi, Faraz I. Zaidi, Jacqueline Chu, Ilknur Yilmaz, Benjamin Perrin, Mamadou A. Bah |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
T cell medicine.medical_treatment Immunology malaria exported proteins lcsh:Medicine DNA vaccination 03 medical and health sciences 0302 clinical medicine Antigen Drug Discovery parasitic diseases medicine Pharmacology (medical) 030212 general & internal medicine Pharmacology biology Malaria vaccine liver stage lcsh:R dna vaccines biology.organism_classification Virology Circumsporozoite protein 030104 developmental biology Infectious Diseases medicine.anatomical_structure plasmodium Adjuvant Plasmodium yoelii CD8 |
| Zdroj: | Vaccines, Vol 8, Iss 1, p 21 (2020) Vaccines Volume 8 Issue 1 |
| Popis: | 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%&ndash 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. |
| Databáze: | OpenAIRE |
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