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Novel influenza A antibodies reduce severity of secondary pneumococcal pneumonia after influenza infection in mice
Critical Care volume 19, Article number: P103 (2015)
Secondary bacterial pneumonia after influenza infection can cause severe disease with a high mortality. Recently, a new group 2 influenza A antibody (AT10_002) has been developed, which binds to multiple H3 and H7 subtypes. In a mouse model of primary influenza infection, treatment with AT10_002 as a fusion antibody protects against lethal infection, and reduces loss of bodyweight . We hypothesized that treatment with AT10_002 reduces weight loss, lung injury and bacterial outgrowth, in a mouse model of viral infection followed by secondary pneumococcal infection.
Male C57Bl/6 mice were intranasally inoculated with 400 TCID50 Influenza A (H3N2). Two days after infection, mice were injected with either AT10_002 i.v. (n = 8) or a control antibody (n = 7). After 7 days, both groups were intranasally inoculated with 5 × 103 S. pneumoniae type 3 and were sacrificed 18 hours later. Outcome measures were weight loss, wet lung weight, cell count in bronchoalveolar lavage fluid (BALF), and colony-forming units (CFUs) in lung homogenate. Data are represented as medians, and treatment groups are compared using nonparametric tests.
Mice receiving AT10_002 showed significantly lower weight loss at the time of sacrifice compared with the control group (+1% vs. -12% change in weight; P = 0.0003). Also wet lung weight was lower (68 vs. 96 mg; P = 0.0003), cell counts in BALF were lower (4.9 × 105 vs. 7.0 × 105 cells/ml; P = 0.0037) and CFUs in lung homogenate were lower (33 vs. 25 × 104 CFUs/mg; P = 0.0003) compared with controls.
Early treatment with influenza antibody AT10_002 significantly reduces weight loss, lung injury and bacterial outgrowth, in a mouse model of influenza infection followed by secondary pneumococcal pneumonia.
Wagner K, et al: Proc Natl Acad Sci U S A. 2014, 111: 16820-5. 10.1073/pnas.1408605111.
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Van der Sluijs, K., Van Someren Greve, F., Jong, M.D. et al. Novel influenza A antibodies reduce severity of secondary pneumococcal pneumonia after influenza infection in mice. Crit Care 19, P103 (2015). https://doi.org/10.1186/cc14183
- Lung Injury
- Bacterial Outgrowth
- Bronchoalveolar Lavage
- Lavage Fluid