Mycobacterium bovis BCG killed by extended freeze-drying reduces airway hyperresponsiveness in 2 animal models
Lagranderie, Micheline × Abolhassani, Mohammad Vanoirbeek, Jeroen Lefort, Jean Nahori, Marie-Anne Silva, Jose-Roberto Lapa Huerre, Michel Vargaftig, Boris Marchal, Gilles #
Journal of allergy and clinical immunology vol:121 issue:2 pages:471-478
Background: Live BCG administered intranasally to mice inhibits the development of ovalbumin (OVA)–induced eosinophilia and airway hyperresponsiveness (AHR). It is
unacceptable to treat human subjects intranasally with live
Objective: We investigated whether BCG killed by extended
freeze-drying (EFD) and subcutaneously injected has a
protective effect in murine and guinea pig models of allergic airway inflammation.
Methods: Mice were OVA sensitized (days 0 and 7), treated
subcutaneously (day 14) with EFD and live or heat-killed
BCG, and then OVA challenged (day 42). OVA-sensitized mice
(days 0 and 7) were challenged (day 14) and EFD treated (day
18) before OVA rechallenge (day 46) to demonstrate the
capacity of EFD to reverse the established lung inflammation. Guinea pigs were OVA sensitized (days 0 and 14), treated intradermally (day 35) with EFD, and OVA challenged (days 90-105).
Results: In mice and guinea pigs EFD treatment reduced
AHR. Among 3 BCG preparations, only EFD efficiently
reduced AHR, eosinophilia, and the recruitment of dendritic
cells to the lungs after OVA challenge. The protective effect of EFD is associated with production of the immunoregulatory cytokine IL-10. Moreover, EFD treatment did not induce toxic effects or delayed-type hypersensitivity to mycobacterial antigens; that is, it did not interfere with the diagnosis of tuberculosis.
Conclusion: EFD administered subcutaneously inhibits the
development of allergic airway inflammation and prevents AHR
without inducing delayed-type hypersensitivity and side effects associated with live or heat-killed BCG.