Formulation of the prefusion RSV F protein with a Th1/Th2-balanced adjuvant provides complete protection without Th2-skewed immunity in RSV-experienced young mice |
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| Institution: | 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. Sigmovir Biosystems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, United States;2. University of Maryland School of Medicine, Baltimore, MD 21101, United States;1. Division of Virology, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar, Herts EN6 3QG, UK;2. Biostatistics, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar, Herts EN6 3QG, UK;1. Department of Virology, Institute of Experimental Medicine, 12 Acad. Pavlov Street, 197376, Russia;2. Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA;1. National Center for Immunization and Respiratory Diseases, Division of Viral Diseases, Gastroenteritis and Respiratory Viruses Laboratory Branch, Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA;2. College of Veterinary Medicine, Department of Infectious Diseases, University of Georgia, Athens, GA, USA;3. Division of Pediatric Infectious Diseases, Emory University and Children''s Healthcare of Atlanta, Atlanta, GA, USA;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 |
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| Abstract: | Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections among infants with most infections occurring in the first year of life. Multiple RSV exposures are required for children to mount adult-like immune responses. Although adult RSV immunity is associated with less severe disease, the protection induced through natural infection is short-lived. Therefore, vaccination of RSV-experienced young children may accelerate immunity and provide long-term protection from RSV reinfection. However, the extent to which different Th-biased vaccine regimens influence pre-existing humoral and cellular immunity in RSV-experienced young children is unknown. To address this question, infant BALB/c mice were RSV-infected and subsequently immunized with the prefusion RSV F (PreF) antigen formulated with either a Th2-skewing (Alum) or Th1/Th2-balanced (Advax-SM) adjuvant. These studies show that both adjuvants boosted neutralizing antibody and protected from RSV reinfection, but Advax-SM adjuvant prevented the Th2-skewed immunity observed in RSV-experienced young mice immunized with PreF/Alum. |
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| Keywords: | Young Th1/Th2-balanced Vaccination Mice RSV |
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