Development of a recombinant BCG based vaccine that prevents the infection with the human metapneumovirus stimulating Th1 immunity (VAC7P.975)

Autor: Christian Palavecino, Pablo Céspedes, Roberto Gomez, Alexis Kalergis, Susan Bueno
Rok vydání: 2014
Předmět:
Zdroj: The Journal of Immunology. 192:141.20-141.20
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.192.supp.141.20
Popis: The human metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, due to an inefficient immunological memory, hMPV infection provides limited immune protection. The inadequate immune response causes severe lung inflammation leading to airway obstruction. It is likely that an effective clearance of hMPV require a balanced Th1 type immune response, involving the participation of activated, IFN-γ secreting, T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guerin (BCG), which has been used for decades to protect newborns from tuberculosis. Here, we show that a re-infection worsens the viral illness in Balb/c mice, questioning the safety of vaccines based on attenuated virus. We also observed a Th1 pattern of cytokines animals infected as normal infection curse. The immunization with our recombinant BCG strains expressing the Phosphoprotein (P) from hMPV induces a protective Th1 immunity. The mice were protected from clinical disease such us weight loss, inflammatory cells recruitment in airway and viral replication in the lungs. Our recombinant vaccine also induced the activation of hMPV-specific T cells producing IFN- γ and IL-2, which protect from hMPV infection when transferred to naïve mice. These data strongly support the notion that recombinant BCG induces protective Th1 immunity and could be considered as an efficient vaccine against hMPV.
Databáze: OpenAIRE