Article ; Online: Survival during influenza-associated bacterial superinfection improves following viral- and bacterial-specific monoclonal antibody treatment.
JCI insight
2019 Volume 4, Issue 14
Abstract: ... to determine if mAbs can improve survival during postinfluenza bacterial pneumonia. We administered FY1 ... with singular infection with influenza during both pandemics and seasonal epidemics. Vaccines and current ... survival when mice were treated with a combination of FY1 and MEDI4893* late during the course ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Broadly Neutralizing Antibodies/pharmacology ; Broadly Neutralizing Antibodies/therapeutic use ; Disease Models, Animal ; Drug Therapy, Combination/methods ; Humans ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Influenza, Human/drug therapy ; Influenza, Human/immunology ; Influenza, Human/mortality ; Influenza, Human/virology ; Lung/immunology ; Lung/microbiology ; Lung/virology ; Macrophages/drug effects ; Macrophages/immunology ; Male ; Methicillin-Resistant Staphylococcus aureus/immunology ; Methicillin-Resistant Staphylococcus aureus/pathogenicity ; Mice ; Neutrophils/drug effects ; Neutrophils/immunology ; Pneumonia, Staphylococcal/drug therapy ; Pneumonia, Staphylococcal/immunology ; Pneumonia, Staphylococcal/microbiology ; Pneumonia, Staphylococcal/mortality ; Superinfection/drug therapy ; Superinfection/immunology ; Superinfection/microbiology ; Superinfection/mortality ; Survival Analysis ; Treatment Outcome |
| Chemical Substances | Anti-Bacterial Agents ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antiviral Agents ; Broadly Neutralizing Antibodies ; suvratoxumab (4L1997J4DF) ; MEDI8852 (OZS4TXB9VO) |
| Language | English |
| Publishing date | 2019-07-25 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ISSN | 2379-3708 |
| ISSN (online) | 2379-3708 |
| DOI | 10.1172/jci.insight.125554 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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