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;

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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