title: Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.
abstract: Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Angiolo
authors.initials: A
authors.lastname: Pierantoni
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Esposito
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Virginia
authors.initials: V
authors.lastname: Ammendola
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Federico
authors.initials: F
authors.lastname: Napolitano
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Fabiana
authors.initials: F
authors.lastname: Grazioli
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Adele
authors.initials: A
authors.lastname: Abbate
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Del Sorbo
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Loredana
authors.initials: L
authors.lastname: Siani
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Anna Morena
authors.initials: AM
authors.lastname: D'Alise
authors.affiliation: Cellular Biology and Neurobiology Institute (IBCN) National Research Council of Italy , Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Taglioni
authors.affiliation: Cellular Biology and Neurobiology Institute (IBCN) National Research Council of Italy , Rome, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: Perretta
authors.affiliation: San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Siccardi
authors.affiliation: San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Soprana
authors.affiliation: San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Panigada
authors.affiliation: The Pirbright Institute , Surrey, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Thom
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Elisa
authors.initials: E
authors.lastname: Scarselli
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.affiliation: The Pirbright Institute , Surrey, UK.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Taylor
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl) ; Keires AG , Basel, Switzerland.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl) ; CEINGE , Naples, Italy ; Department of Molecular Medicine and Medical Biotechnology, University Federico II , Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Stefania
authors.initials: S
authors.lastname: Capone
authors.affiliation: ReiThera Srl , Rome, Italy (former Okairos Srl).
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vitelli