Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model |
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| Affiliation: | 1. U.S. Geological Survey, 12201 Sunrise Valley Drive, MS 926A, Reston, VA 20192, USA;2. South Carolina Geological Survey, 5 Geology Road, Columbia, SC 29212, USA;3. U.S. Geological Survey, 12201 Sunrise Valley Drive, MS 956, Reston, VA 20192, USA;4. U.S. Geological Survey, Box 25046, Denver Federal Center, MS 974, Denver, CO 80225, USA;1. Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow, Russian Federation;2. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation;3. Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow, Russian Federation;4. K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology, Moscow, Russian Federation;5. Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia;6. Department of Biophysics, Biological Faculty, Moscow State University, Moscow, Russian Federation;1. Integrated Nanosystems Research Facility, Electrical Engineering and Computer Science, University of California, Irvine, Irvine, CA 92697, United States;2. Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697, United States;3. Center for Mitochondrial and Epigenomic Medicine, Children''s Hospital of Philadelphia and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States |
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| Abstract: | ![]()
Identifying new molecular adjuvants that elicit effective vaccine-induced CD8+ T cell immunity may be critical for the elimination of many challenging diseases including Tuberculosis, HIV and cancer. Here, we report that co-administration of molecular adjuvant IL-33 during vaccination enhanced the magnitude and function of antigen (Ag)-specific CD8+ T cells against a model Ag, LCMV NP target protein. These enhanced responses were characterized by higher frequencies of Ag-specific, polyfunctional CD8+ T cells exhibiting cytotoxic characteristics. Importantly, these cells were capable of robust expansion upon Ag-specific restimulation in vivo and conferred remarkable protection against a high dose lethal LCMV challenge. In addition, we demonstrate the ability of IL-33 to amplifying the frequency of Ag-specific KLRG1+ effector CD8+ T cells. These data show that IL-33 is a promising immunoadjuvant at improving T cell immunity in a vaccine setting and suggest further development and understanding of this molecular adjuvant for strategies against many obstinate infectious diseases and cancer. |
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| Keywords: | DNA vaccines Adjuvants IL-33 CD8 T cells HIV LCMV |
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