Formulation of the respiratory syncytial virus fusion protein with a polymer-based combination adjuvant promotes transient and local innate immune responses and leads to improved adaptive immunity |
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| Affiliation: | 1. VIDO-InterVac, University of Saskatchewan, Saskatoon S7N 5E3, Canada;2. Microbiology and Immunology, University of Saskatchewan, Saskatoon S7N 5E5, Canada;1. Vaxart, Inc., 290 Utah Ave, Suite 200, South San Francisco, CA 94080, USA;2. Division of Infectious Diseases, Allergy & Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, MO, USA;3. Dept. Pharmacology and Therapeutics and School of Pharmacy, University College Cork, Cork, Ireland;1. Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK;2. ENT Department, Alder Hey Children''s Hospital, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK;3. ENT Department, Royal Liverpool and Broadgreen University Hospitals, Liverpool, UK;4. Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, UK;5. Department of Women''s and Children''s Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK;6. The Jenner Institute, University of Oxford, ORCRB, Oxford, UK;1. Sanofi Pasteur, Discovery North America, 38 Sidney Street, Cambridge, MA 02139, USA;2. Sanofi Pasteur, ARD North America, 1755 Steeles Avenue West, Toronto, ON M2R 3T4, Canada;1. VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3;2. Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3;3. Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3;1. Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA;2. Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA;3. Department of Medicine, Division of Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;4. Calder Biosciences, Brooklyn, NY, USA;5. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;6. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;1. VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada;2. Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada;3. Veterinary Pathology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada;4. Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada;5. Guangdong South China United Vaccine Institute, Guangdong, Guangzhou, China |
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| Abstract: | Respiratory syncytial virus (RSV) causes serious upper and lower respiratory tract infections in newborns and infants. Presently, there is no licensed vaccine against RSV. We previously reported the safety and efficacy of a novel vaccine candidate (ΔF/TriAdj) in rodent and lamb models following intranasal immunization. However, the effects of the vaccine on the innate immune system in the upper and lower respiratory tracts, when delivered intranasally, have not been characterized. In the present study, we found that ΔF/TriAdj triggered transient production of chemokines, cytokines and interferons in the nasal tissues and lungs of BALB/c mice. The types of chemokines produced were consistent with the populations of immune cells recruited, i.e. dendritic cells, macrophages and neutrophils, in the nose-associated lymphoid tissue (NALT), lung and their draining lymph nodes of the ΔF/TriAdj-immunized group. In addition, ΔF/TriAdj stimulated cellular activation with generation of mucosal and systemic antibody responses, and conferred complete protection from viral infection in the lungs upon RSV challenge. The effect of ΔF/TriAdj was short-lived in the nasal tissues and more prolonged in the lungs. In addition, both innate and adaptive immune responses were lower when mice were immunized with ΔF alone. These results suggest that ΔF/TriAdj modulates the innate mucosal environment in both upper and lower respiratory tracts, which contributes to robust adaptive immune responses and long-term protective efficacy of this novel vaccine formulation. |
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| Keywords: | RSV Intranasal immunization Vaccine Innate immune system Upper and lower respiratory tracts |
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