Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment
| Autor: | Kara L Nickolich, Matthew J Pilewski, Bret R. Sellman, Taylor S. Cohen, Keven M. Robinson, Joshua M. Tobin, Nicole L. Kallewaard, Krishnaveni Ramanan, John F. Alcorn |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Methicillin-Resistant Staphylococcus aureus 0301 basic medicine Neutrophils medicine.drug_class Lung injury Antibodies Monoclonal Humanized Monoclonal antibody Antiviral Agents Virus Mice 03 medical and health sciences Influenza A Virus H1N1 Subtype 0302 clinical medicine Influenza Human Pneumonia Staphylococcal Pandemic medicine Animals Humans Lung biology business.industry Macrophages Bacterial pneumonia Antibodies Monoclonal General Medicine biology.organism_classification medicine.disease Survival Analysis Anti-Bacterial Agents Disease Models Animal Treatment Outcome 030104 developmental biology Infectious disease (medical specialty) Superinfection 030220 oncology & carcinogenesis Immunology Bacterial superinfection Drug Therapy Combination business Broadly Neutralizing Antibodies Bacteria Research Article |
| Zdroj: | JCI Insight. 4 |
| ISSN: | 2379-3708 |
| Popis: | Postinfluenza bacterial superinfections cause increased morbidity and mortality compared with singular infection with influenza during both pandemics and seasonal epidemics. Vaccines and current treatments provide limited benefit, a rationale to conduct studies utilizing alternative therapies. FY1 and an optimized version, MEDI8852, anti-influenza HA mAbs, have been shown to neutralize influenza virus during singular influenza infection. MEDI4893*, an anti–Staphylococcus aureus α-toxin mAb, has been shown to improve survival when administered prophylactically prior to S. aureus pneumonia. Our objective was to determine if mAbs can improve survival during postinfluenza bacterial pneumonia. We administered FY1 in a murine model of postinfluenza methicillin-resistant S. aureus (MRSA) pneumonia and observed improved survival rates when given early during the course of influenza infection. Our findings indicate decreased lung injury and increased uptake and binding of bacteria by macrophages in the mice that received FY1 earlier in the course of influenza infection, corresponding to decreased bacterial burden. We also observed improved survival when mice were treated with a combination of FY1 and MEDI4893* late during the course of postinfluenza MRSA pneumonia. In conclusion, both FY1 and MEDI4893* prolong survival when used in a murine model of postinfluenza MRSA pneumonia, suggesting pathogen-specific mAbs as a possible therapeutic in the context of bacterial superinfection. |
| Databáze: | OpenAIRE |
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