Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection

Rutigliano, John A.; Doherty, Peter C.; Franks, John; Morris, Melissa Y.; Reynolds, Cory; Thomas, Paul G.

doi:10.1016/j.jim.2008.04.003

Cited by 33 publications

(38 citation statements)

References 31 publications

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“…For example, no ferret-specific reagents are commercially available, and the cross-reactive antibodies are unverified (69,70). To overcome the limitations in the availability of immunological reagents, we have explored the use of molecular imaging as a tool for studying the pathogenesis of IAV in the ferret lung (29).…”

Section: Discussionmentioning

confidence: 99%

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

Camp

Bağcı

Chu

et al. 2015

J Virol

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Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virusinfected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [18 F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. IMPORTANCESevere influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs.T he annual impact of seasonal influenza A viruses (IAV) on public health is fairly predictable and is mostly preventable in normal, healthy populations with currently...

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Section: Discussionmentioning

confidence: 99%

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

Camp

Bağcı

Chu

et al. 2015

J Virol

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“…The assessment of virus-specific T cell responses after vaccination or infection of ferrets has been hampered by the lack of reagents necessary for the detection of ferret T cells and their products. Recently, monoclonal antibodies specific for human cluster-of-differentiation (CD) antigens that cross-react with those of ferret lymphocytes have been defined (35,43). Antibodies specific for ferret gamma interferon (IFN-␥) that can be used to detect the production of this cytokine by ferret T cells (for example, by enzyme-linked immunospot [ELISPOT] assay) also have been produced (28).…”

Section: Discussionmentioning

confidence: 99%

“…However, although reagents are becoming available, assays for the detection of virus-specific T cells have not been described so far to our knowledge. Using monoclonal antibodies cross-reactive with ferret CD3 and CD8 (35,43), we developed a T cell proliferation assay that allowed discrimination of proliferation of CD8 ϩ and CD8…”

Section: Discussionmentioning

confidence: 99%

A Single Immunization with CoVaccine HT-Adjuvanted H5N1 Influenza Virus Vaccine Induces Protective Cellular and Humoral Immune Responses in Ferrets

Bodewes

Kreijtz

Amerongen

et al. 2010

J Virol

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“…Confirmation of leukocyte cell recruitment to the URT and LRT by flow cytometry assays would complement the real-time PCR data shown here. Antibodies have been described for some leukocytes of the ferret (50)(51)(52)(53), yet these are limited and can give variable results in different laboratories. Studies to assess cytokine and chemokine production by ferret leukocytes by using flow cytometry analyses are ongoing.…”

Section: Figmentioning

confidence: 99%

Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses

Carolan

Rockman

Borg

et al. 2016

J Virol

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The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1␣ (IL-1␣), IL-1␤, IL-6, IL-12p40, alpha interferon (IFN-␣), IFN-␤, and tumor necrosis factor alpha (TNF-␣) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-␥ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. IMPORTANCEBoth influenza A and B viruses cocirculate in the human population, and annual influenza seasons are typically dominated by an influenza A virus subtype or an influenza B virus lineage. Surveillance data indicate that the burden of disease is higher in some seasons, yet it is unclear whether this is due to specific virus strains or to other factors, such as cross-reactive immunity or clinical definitions of influenza. We directly compared disease severities and localized inflammatory responses to different seasonal influenza virus strains, including the 2009 pandemic strain, in healthy naive ferrets. We found that the disease severities and the cytokine and chemokine responses were similar irrespective of the seasonal strain or the location of the infection in the respiratory tract. This suggests that factors other than the immune response to a particular virus (sub)type contribute to the variable impact of influenza virus infection in a population. Morbidity and mortality associated with human influenza virus infection are significant worldwide. Influenza is caused by three virus types (A, B, and C), among which types A and B are responsible for most of the diagnosed cases of seasonal influenza. Influenza A viruses attract the greatest attentio...

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Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection

Cited by 33 publications

References 31 publications

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

A Single Immunization with CoVaccine HT-Adjuvanted H5N1 Influenza Virus Vaccine Induces Protective Cellular and Humoral Immune Responses in Ferrets

Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses

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