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

Pablo F. Céspedes, Emma Rey-Jurado, Janyra A Espinoza, Claudia A Rivera, Gisela Canedo-Marroquín, Susan M Bueno, Alexis M. Kalergis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 × 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 28 days 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 languageEnglish
Pages (from-to)757-766
Number of pages10
JournalVaccine
Volume35
Issue number5
DOIs
StatePublished - 1 Feb 2017

Bibliographical note

Funding Information:
This work was supported by grants CONICYT/FONDECYT POSTDOCTORADO No. 3140455 and No. 3160249, DOCTORADO CONICYT No. 21130507, FONDECYT 1070352; FONDEF D061008; FONDEF D11I1080; and the Millennium Institute on Immunology and Immunotherapy (P09/016-F).

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • Bacillus Calmette et Guerin
  • Human respiratory syncytial virus
  • Pulmonary inflammation
  • Recombinant vaccine
  • T cells
  • Th1
  • Th17
  • Viral infection

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