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Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Immunization with a recombinant bacillus Calmette-Guerin strain confers protective Th1 immunity against the human
Christian E Palavecino1, Pablo F Céspedes, Roberto S Gómez
1Instituto Milenio en Inmunología e Inmunoterapia, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile;
Abstract:
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-γ-secreting T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guérin (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-γ 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.
Insights
A novel recombinant BCG vaccine expressing human metapneumovirus (hMPV) antigens induces protective Th1 immunity. This approach offers a promising strategy to combat hMPV infections and reduce childhood hospitalizations.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Human metapneumovirus (hMPV) causes significant childhood respiratory illness and reinfection due to poor immune memory.
- hMPV infection can trigger an inadequate Th2 immune response, leading to severe lung inflammation and airway obstruction.
- Effective hMPV clearance likely requires a balanced Th1 immune response, characterized by IFN-γ-secreting T cells.
Purpose of the Study:
- To investigate the potential of recombinant bacillus Calmette-Guérin (rBCG) expressing hMPV antigens as a vaccine candidate.
- To evaluate if rBCG immunization can induce protective Th1 immunity against hMPV infection.
Main Methods:
- Mice were immunized with rBCG strains engineered to express the hMPV phosphoprotein.
- Immunized mice were subsequently challenged with hMPV to assess protection against disease.
- T cell responses, including IFN-γ and IL-2 production, were analyzed in immunized mice.
- Adoptive transfer of hMPV-specific T cells was performed to confirm their protective capacity.
Main Results:
- Mice immunized with rBCG expressing hMPV antigens showed protection against weight loss, lung inflammation, and viral replication post-hMPV infection.
- The rBCG vaccine induced hMPV-specific T cells producing key Th1 cytokines, IFN-γ and IL-2.
- Adoptive transfer of these activated T cells conferred protection against hMPV infection in recipient mice.
Conclusions:
- rBCG expressing hMPV antigens effectively induces protective Th1 immunity.
- This rBCG-based vaccine strategy shows significant potential for preventing hMPV infections.
- The findings support the consideration of rBCG as an efficient vaccine against hMPV.
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