title: A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice.
abstract: Human respiratory syncytial virus (hRSV) is a major health burden worldwide, causing the majority of hospitalizations in children under two years old due to bronchiolitis and pneumonia. HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised adults. Furthermore, both hRSV morbidity and epidemics are explained by a consistently high rate of re-infections that take place throughout the patient life. Although significant efforts have been invested worldwide, currently there are no licensed vaccines to prevent hRSV infection. Here, we describe that a recombinant Bacillus Calmette-Guerin (BCG) vaccine expressing the nucleoprotein (N) of hRSV formulated under current good manufacture practices (cGMP rBCG-N-hRSV) confers protective immunity to the virus in mice. Our results show that a single dose of the GMP rBCG-N-hRSV vaccine retains its capacity to protect mice against a challenge with a disease-causing infection of 1×107plaque-forming units (PFUs) of the hRSV A2 clinical strain 13018-8. Compared to unimmunized infected controls, vaccinated mice displayed reduced weight loss and less infiltration of neutrophils within the airways, as well as reduced viral loads in bronchoalveolar lavages, parameters that are characteristic of hRSV infection in mice. Also, ex vivo re-stimulation of splenic T cells at 28days post-immunization activated a repertoire of T cells secreting IFN-γ and IL-17, which further suggest that the rBCG-N-hRSV vaccine induced a mixed, CD8+and CD4+T cell response capable of both restraining viral spread and preventing damage of the lungs. All these features support the notion that rBCG-N-hRSV is a promising candidate vaccine to be used in humans to prevent the disease caused by hRSV in the susceptible population.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Pablo F
authors.initials: PF
authors.lastname: Céspedes
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Emma
authors.initials: E
authors.lastname: Rey-Jurado
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Janyra A
authors.initials: JA
authors.lastname: Espinoza
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Rivera
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Gisela
authors.initials: G
authors.lastname: Canedo-Marroquín
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile; Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Chile; INSERM UMR 1064, Nantes, France. Electronic address: akalergis@bio.puc.cl.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007115:Immunization Schedule; D000071497:Immunogenicity, Vaccine; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D014614:Vaccines, Synthetic; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D020381:Interleukin-17; D009698:Nucleoproteins; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D007371:Interferon-gamma
keywords: Bacillus Calmette et Guerin; Human respiratory syncytial virus; Pulmonary inflammation; Recombinant vaccine; T cells; Th1; Th17; Viral infection