Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the
Marie-Ève Hamelin1, Christian Couture2, Melanie K Sackett2
1Research Center in Infectious Diseases of the 'Centre Hospitalier Universitaire de Québec' and Laval University, 2705 blvd Laurier, Québec City, QC G1V 4G2, Canada.
Abstract:
Human metapneumovirus (hMPV) is a paramyxovirus that causes acute respiratory-tract infections in humans. The histopathological and immunological responses to hMPV infection in BALB/c mice immunized with inactivated hMPV were characterized. Animals were immunized intraperitoneally with PBS, supernatant from non-infected LLC-MK2 cells and from heat-inactivated influenza A- or hMPV-infected cells, all in incomplete Freund's adjuvant, or with heat-inactivated hMPV without adjuvant, and then infected intranasally with 10(8) TCID50 virus. Following infection, lung samples and bronchoalveolar lavages were collected for determination of viral titre and cytokine levels and for histopathological studies. On day 1, 26 % of mice immunized with inactivated hMPV and adjuvant died, compared with none in the other groups. There was more significant lung inflammation associated with eosinophilic infiltration, as well as increased levels of interleukin-4 (IL-4) and IL-5, in the bronchoalveolar lavages of mice immunized with hMPV alone or with the adjuvant. Mice from the last two groups had a 4-5 log10 decrease in their pulmonary viral titres compared with controls. Our data demonstrate the risks associated with immunization using inactivated hMPV in this animal model and that this aberrant response should be considered in the development of hMPV vaccines.
Insights
Immunizing mice with inactivated human metapneumovirus (hMPV) caused adverse effects, including increased lung inflammation and mortality. This aberrant immune response highlights risks for hMPV vaccine development.
Area of Science:
- Virology
- Immunology
- Respiratory Medicine
Background:
- Human metapneumovirus (hMPV) is a significant cause of acute respiratory infections.
- Understanding immune responses to hMPV is crucial for vaccine development.
Purpose of the Study:
- To characterize the histopathological and immunological responses to hMPV infection in mice immunized with inactivated hMPV.
- To assess the safety and efficacy of inactivated hMPV immunization in a murine model.
Main Methods:
- BALB/c mice were immunized with inactivated hMPV (with or without adjuvant) or control substances.
- Mice were subsequently infected intranasally with live hMPV.
- Lung tissues and bronchoalveolar lavages were analyzed for viral load, cytokine levels, and histopathology.
Main Results:
- Immunization with inactivated hMPV and adjuvant led to significant mortality (26%) on day 1 post-infection.
- Enhanced lung inflammation, eosinophilic infiltration, and elevated IL-4 and IL-5 levels were observed in mice immunized with inactivated hMPV.
- Pulmonary viral titers were reduced by 4-5 log10 in mice immunized with inactivated hMPV compared to controls.
Conclusions:
- Inactivated hMPV immunization can induce detrimental immune responses in this animal model.
- The observed aberrant response poses risks and must be considered in the development of safe and effective hMPV vaccines.
