Browsing by Author "Cespedes, Pablo F."

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    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
    (2017) Cespedes, Pablo F.; Rey-Jurado, Emma; Espinoza, Janyra A.; Rivera, Claudia A.; Canedo-Marroquin, Gisela; Bueno, Susan M.; Kalergis, Alexis M.
    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 x 10(7) 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-gamma 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. (C) 2016 Elsevier Ltd. All rights reserved.
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    Human metapneumovirus infection activates the TSLP pathway that drives excessive pulmonary inflammation and viral replication in mice
    (2015) Lay, Margarita K.; Cespedes, Pablo F.; Palavecino, Christian E.; León, Miguel A.; Diaz, Rodrigo A.; Salazar, Francisco J.; Mendez Olivieri, Gonzalo Patricio; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes
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    Immunization with a Recombinant Bacillus Calmette-Guerin Strain Confers Protective Th1 Immunity against the Human Metapneumovirus
    (2014) Palavecino, Christian E.; Cespedes, Pablo F.; Gomez, Roberto S.; Kalergis, Alexis M.; Bueno, Susan M.
    Along with the human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, owing to an inefficient immunological memory, hMPV infection provides limited immune protection against reinfection. Furthermore, hMPV can induce an inadequate Th2 type immune response that causes severe lung inflammation, leading to airway obstruction. Similar to hRSV, it is likely that an effective clearance of hMPV would require a balanced Th1 type immunity by the host, involving the activation of IFN-gamma-secreting T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guerin (BCG), which has been used in newborns for many decades and in several countries as a tuberculosis vaccine. We have previously shown that immunization with BCG strains expressing hRSV Ags can induce an efficient immune response that protects against this virus. In this study, we show that immunization with rBCG strains expressing the phosphoprotein from hMPV also can induce protective Th1 immunity. Mice immunized with rBCG were protected against weight loss, airway inflammation, and viral replication in the lungs after hMPV infection. Our rBCG vaccine also induced the activation of hMPV-specific T cells producing IFN-gamma and IL-2, which could protect from hMPV infection when transferred to recipient mice. These data strongly support the notion that rBCG induces protective Th1 immunity and could be considered as an efficient vaccine against hMPV.
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