title: Maternal immunization with chimpanzee adenovirus expressing RSV fusion protein protects against neonatal RSV pulmonary infection.
abstract: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease with high morbidity and mortality in young infants and children. Despite numerous efforts, a licensed vaccine against RSV remains elusive. Since young infants form the primary target group of RSV disease, maternal immunization to boost the protection in neonates is an attractive strategy. In this study we tested the efficacy of maternal immunization with a chimpanzee adenovirus expressing codon-optimized RSV fusion protein (AdC7-Fsyn) to protect infants against RSV infection. Single intranasal immunization of mice by AdC7-Fsyn induced robust anti-RSV systemic and mucosal immunity that protected against RSV without causing vaccine-enhanced RSV disease. RSV humoral immunity was transferred to pups born to immunized mothers that provided protection against RSV. Immunization with AdC7-Fsyn was effective even in the presence of Ad5 preimmunity. The maternally derived immunity was durable with the half-life of 14.63 days that reduced the viral replication up to 15 weeks of age. Notably, the passively immunized mice could be actively re-immunized with AdC7-Fsyn to boost and extend the protection. This substantiates maternal immunization with an AdC7-based vaccine expressing RSV F as feasible approach to protect against RSV early in life.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Anurag
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wendland
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Biin
authors.initials: B
authors.lastname: Sung
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grunwald
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY, United States; Department of Pediatrics, Weill Cornell Medical College, New York, NY, United States. Electronic address: stw2006@med.cornell.edu.
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
mesh_terms: D000256:Adenoviridae; D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D005260:Female; D056724:Immunity, Humoral; D007112:Immunity, Maternally-Acquired; D018928:Immunity, Mucosal; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins
keywords: Chimpanzee adenoviral vector; Maternal immunization; RSV vaccine; Respiratory syncytial virus