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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 1×107 plaque-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.

Original publication

DOI

10.1016/j.vaccine.2016.12.048

Type

Journal article

Journal

Vaccine

Publication Date

01/02/2017

Volume

35

Pages

757 - 766

Keywords

Bacillus Calmette et Guerin, Human respiratory syncytial virus, Pulmonary inflammation, Recombinant vaccine, T cells, Th1, Th17, Viral infection, Animals, BCG Vaccine, CD8-Positive T-Lymphocytes, Humans, Immunity, Cellular, Immunization Schedule, Immunogenicity, Vaccine, Interferon-gamma, Interleukin-17, Lung, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Nucleoproteins, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus Vaccines, Respiratory Syncytial Virus, Human, Th1 Cells, Th17 Cells, Vaccines, Synthetic, Viral Proteins