title: Formulation of the respiratory syncytial virus fusion protein with a polymer-based combination adjuvant promotes transient and local innate immune responses and leads to improved adaptive immunity.
abstract: Respiratory syncytial virus (RSV) causes serious upper and lower respiratory tract infections in newborns and infants. Presently, there is no licensed vaccine against RSV. We previously reported the safety and efficacy of a novel vaccine candidate (ΔF/TriAdj) in rodent and lamb models following intranasal immunization. However, the effects of the vaccine on the innate immune system in the upper and lower respiratory tracts, when delivered intranasally, have not been characterized. In the present study, we found that ΔF/TriAdj triggered transient production of chemokines, cytokines and interferons in the nasal tissues and lungs of BALB/c mice. The types of chemokines produced were consistent with the populations of immune cells recruited, i.e. dendritic cells, macrophages and neutrophils, in the nose-associated lymphoid tissue (NALT), lung and their draining lymph nodes of the ΔF/TriAdj-immunized group. In addition, ΔF/TriAdj stimulated cellular activation with generation of mucosal and systemic antibody responses, and conferred complete protection from viral infection in the lungs upon RSV challenge. The effect of ΔF/TriAdj was short-lived in the nasal tissues and more prolonged in the lungs. In addition, both innate and adaptive immune responses were lower when mice were immunized with ΔF alone. These results suggest that ΔF/TriAdj modulates the innate mucosal environment in both upper and lower respiratory tracts, which contributes to robust adaptive immune responses and long-term protective efficacy of this novel vaccine formulation.
authors: VIDO-InterVac, University of Saskatchewan, Saskatoon S7N 5E3, Canada; Microbiology and Immunology, University of Saskatchewan, Saskatoon S7N 5E5, Canada.
authors: Indranil
authors: I
authors: Sarkar
authors: VIDO-InterVac, University of Saskatchewan, Saskatoon S7N 5E3, Canada.
authors: Ravendra
authors: R
authors: Garg
authors: VIDO-InterVac, University of Saskatchewan, Saskatoon S7N 5E3, Canada; Microbiology and Immunology, University of Saskatchewan, Saskatoon S7N 5E5, Canada. Electronic address: sylvia.vandenhurk@usask.ca.
authors: Sylvia
authors: S
authors: van Drunen Littel-van den Hurk
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D007372:Interferons / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D012136:Respiratory Syncytial Viruses / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012137:Respiratory System / Q000276:immunology / Q000821:virology; D014760:Viral Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018925:Chemokines; D016207:Cytokines; D011108:Polymers; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; D007372:Interferons
keywords: Innate immune system; Intranasal immunization; RSV; Upper and lower respiratory tracts; Vaccine