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Maternal immunization with respiratory syncytial virus fusion protein formulated with a novel combination adjuvant provides protection from RSV in newborn lambs
Affiliation: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;1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;2. Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa;3. Department of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden;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. 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. Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands;2. Janssen Research & Development, Beerse, Belgium;3. Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands
Abstract:Respiratory syncytial virus (RSV) is the causative agent of serious upper and lower respiratory tract infections in newborns and infants. Protection from RSV is crucial for neonates, and maternal immunization is one approach that holds promise for providing immediate protection to young infants against severe RSV infection. We previously reported efficacy of a subunit vaccine consisting of the fusion (F) protein formulated with a novel adjuvant (ΔF/TriAdj) in neonates. The goal of the current study was to evaluate the ΔF/TriAdj as a maternal vaccine. Pregnant ewes were vaccinated intramuscularly with ΔF/TriAdj or PBS six weeks prior to lambing, and re-vaccinated four weeks later, which resulted in transfer of maternal antibodies (MatAbs) to the newborn lambs through the colostrum. Significantly higher levels of RSV ΔF-specific serum IgG were detected in vaccinated pregnant ewes and their lambs when compared to control animals, which revealed that MatAbs were passively transferred to the offspring. All newborn lambs were challenged with RSV at three days of age. After RSV challenge, virus production and lung pathology were significantly lower in lambs that had received passively transferred antibodies than in control animals. These results indicate that maternal immunization with ΔF/TriAdj might be an alternative, safe and effective approach to provide protection against RSV in newborn and young infants.
Keywords:RSV  Animal model  Maternal immunization  Maternal antibodies  Newborn lambs  Protection
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