|Kehrli Jr, Marcus|
Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/31/2012
Publication Date: 11/1/2012
Citation: Gauger, P.C., Vincent, A.L., Loving, C.L., Henningson, J.N., Lager, K.M., Janke, B.H., Kehrli Jr, M.E., Roth, J.A. 2012. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus. Veterinary Pathology. 49(6):900-912. Interpretive Summary: Influenza A virus causes a respiratory disease in swine similar to that in humans. Use of inactivated influenza virus vaccines in swine has increased over the past ten years in an effort to prevent disease and transmission of the virus. Inactivated vaccines work well when pigs are exposed to influenza viruses represented in the vaccine. However, vaccine efficacy is reduced when pigs are infected with new strains. In this report, pigs administered an inactivated influenza A vaccine followed by infection with the pandemic human influenza A virus (2009) demonstrated more severe clinical disease and lung lesions compared to non-vaccinated pigs infected with the same virus. Eighty-four, six-week-old, crossbred pigs were placed into 3 groups of 28 pigs representing a vaccinated/challenged group (V/C), non-vaccinated/challenged group (NV/C) and a non-vaccinated/non-challenged control group (NV/NC). Pneumonia was evaluated at 1, 2, 5 and 21 days post-inoculation (dpi). Visually, V/C pigs demonstrated greater percentages of pneumonia compared to NV/C pigs, and the microscopic character of the pneumonia was more severe with distinct types of lung damage. Microscopic lung damage was higher in the V/C pigs at 2 and 5 dpi than the NV/C pigs. Elevated immune factors associated with inflammation and disease were detected in the lungs at all time points in V/C pigs compared to NV/C pigs. These data suggest H1 inactivated vaccines followed by mismatched challenge resulted in aggravated clinical signs and enhanced lung lesions and correlated with elevated inflammatory immune mediators. The lung tissue damage and host immune response is consistent with the vaccine-associated enhanced respiratory disease (VAERD) clinical outcome observed reproducibly in our swine model. Active surveillance and monitoring of the quality of match between vaccine strains and strains infecting swine herds is necessary to prevent vaccine mismatch in the swine population. Future vaccines that stimulate improved immune responses across differing influenza viruses will be important to prevent infection and clinical disease and reduce the burden of this economically important disease. Since influenza viruses from swine may infect people, controlling influenza in the swine population has important implications to human health as well.
Technical Abstract: The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine delta-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, six-week-old, crossbred pigs were randomly allocated into 3 groups of 28 pigs representing a vaccinated/challenged group (V/C), non-vaccinated/challenged group (NV/C) and a non-vaccinated/non-challenged control group (NV/NC). Pigs were euthanized at 1, 2, 5 and 21 days post-inoculation (dpi). Macroscopically, V/C pigs demonstrated greater percentages of pneumonia compared to NV/C pigs. Histologically, V/C pigs demonstrated severe, acute, multifocal, suppurative bronchointerstitial pneumonia with necrotizing bronchiolitis accompanied by interlobular and alveolar edema and hemorrhage at 1 and 2 dpi. Marked peribronchiolar lymphocytic cuffing and lymphocytic infiltration of the bronchiolar lamina propria became evident in V/C pigs by 5 dpi. Microscopic lung lesion scores were significantly higher in the V/C pigs at 2 and 5 dpi. Elevated TNF-alphe, IL-1beta, IL-6, and IL-8 were detected in bronchoalveolar lavage fluid at all time points in V/C pigs compared to NV/C pigs. These data suggest H1 inactivated vaccines followed by heterologous challenge resulted in potentiated clinical signs and enhanced pulmonary lesions and correlated with an elevated proinflammatory cytokine response in the lung. The lung pathology and host immune response is consistent with the vaccine-associated enhanced respiratory disease (VAERD) clinical outcome observed reproducibly in our swine model.