title: Mucosal polyinosinic-polycytidylic acid improves protection elicited by replicating influenza vaccines via enhanced dendritic cell function and T cell immunity.
abstract: Live-attenuated influenza vaccines (LAIVs) have the potential to generate CD8 T cell immunity that may limit the virulence of an antigenically shifted influenza strain in a population lacking protective Abs. However, current LAIVs exert limited T cell immunity restricted to the vaccine strains. One approach to improve LAIV-induced T cell responses is the use of specific adjuvants to enhance T cell priming by respiratory dendritic cells, but this hypothesis has not been addressed. In this study, we assessed the effect of the TLR3 ligand polyinosinic-polycytidylic acid (poly IC) on CD8 T cell immunity and protection elicited by LAIVs. Mucosal treatment with poly IC shortly after vaccination enhanced respiratory dendritic cell function, CD8 T cell formation, and production of neutralizing Abs. This adjuvant effect of poly IC was dependent on amplification of TLR3 signaling by nonhematopoietic radioresistant cells and enhanced mouse protection to homosubtypic, as well as heterosubtypic, virus challenge. Our findings indicate that mucosal TLR3 ligation may be used to improve CD8 T cell responses to replicating vaccines, which has implications for protection in the absence of pre-existing Ab immunity.
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany;
authors: José V
authors: JV
authors: Pérez-Girón
authors: Division of Infectious Diseases, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
authors: Alan
authors: A
authors: Belicha-Villanueva
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany;
authors: Ebrahim
authors: E
authors: Hassan
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany;
authors: Sergio
authors: S
authors: Gómez-Medina
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany;
authors: Jazmina L G
authors: JL
authors: Cruz
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany;
authors: Anja
authors: A
authors: Lüdtke
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany;
authors: Paula
authors: P
authors: Ruibal
authors: Division of Infectious Diseases, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Division of Infectious Diseases, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and.
authors: Randy A
authors: RA
authors: Albrecht
authors: Division of Infectious Diseases, Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Division of Infectious Diseases, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
authors: Adolfo
authors: A
authors: García-Sastre
authors: Heinrich Pette Institute, Leibniz Institute For Experimental Virology, 20251 Hamburg, Germany; cesar.munoz-fontela@hpi.uni-hamburg.de.
authors: César
authors: C
authors: Muñoz-Fontela
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009297:Nasal Mucosa / Q000276:immunology*; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D011070:Poly I-C