Methods of treating inflammation associated airway diseases and viral infections
Inventors
Bose, Santanu • Tessier, Philippe
Assignees
Washington State University WSU
Publication Number
US-12084493-B2
Publication Date
2024-09-10
Expiration Date
2035-12-31
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Abstract
The present disclosure provides methods of treating a pathogen-induced lung inflammation in a subject are provided in which an anti-S100A9 antibody is administered to a subject. Methods of treating a respiratory virus infection by administering an anti-S100A9 antibody are also provided.
Core Innovation
The invention provides methods of treating pathogen-induced lung inflammation by administering an antibody that neutralizes S100A9 activity (anti-S100A9 antibody) to a subject. The administration of such an antibody is intended to reduce or ameliorate lung inflammation and infection-associated lung disease, particularly in response to respiratory pathogens including viruses like Influenza virus (e.g., influenza A), coronaviruses (e.g., SARS-CoV-2, COVID-19), and others, as well as bacteria and fungi.
The problem addressed stems from severe lung inflammation during infections such as influenza A or coronavirus diseases, which can result in complications like pneumonia, tissue damage, edema, and mortality. Current treatment options are limited, especially as viral mutations may undermine the effectiveness of vaccines and antivirals. Studies have shown that S100A9 is highly upregulated in infected lungs and contributes to the exaggerated inflammatory response.
The invention is based on the discovery that extracellular S100A9, released from infected macrophages, acts via the TLR4-MyD88 pathway to promote pro-inflammatory cytokine release and apoptosis, exacerbating disease. By neutralizing S100A9 with a targeted antibody, the inflammatory and apoptotic response in the lung can be significantly reduced without substantially affecting viral burden, thereby offering a novel therapeutic and prophylactic strategy for diseases characterized by pathogen-induced lung inflammation.
Claims Coverage
The patent includes two independent claims featuring distinct inventive features related to methods of treating and prophylactically treating Coronavirus-induced lung inflammation using an anti-S100A9 antibody.
Treating Coronavirus-induced lung infection using an anti-S100A9 antibody
A method of treating a Coronavirus-induced lung infection by reducing lung inflammation without substantially affecting Coronavirus viral burden in a subject. The method involves administering a composition comprising an anti-S100A9 antibody to a subject in need thereof, leading to reduction in lung inflammation, with no substantial effect on the Coronavirus viral burden.
Prophylactically treating Coronavirus-induced lung inflammation with anti-S100A9 antibody
A method of prophylactically treating Coronavirus-induced lung inflammation by reducing lung inflammation without substantially affecting Coronavirus viral burden in a subject. The method comprises administering a composition comprising an anti-S100A9 antibody to the subject, effectively reducing Coronavirus-induced lung inflammation, again without substantially affecting the viral burden.
In summary, the independent claims cover both therapeutic and prophylactic methods for reducing Coronavirus-induced lung inflammation using anti-S100A9 antibody compositions, emphasizing reduction of inflammation without changing viral levels.
Stated Advantages
Reduces or ameliorates lung inflammation and infection-associated lung disease in subjects with pathogen-induced inflammation.
Mitigates the severity of respiratory diseases such as pneumonia caused by exaggerated airway inflammation during infections including COVID-19.
Provides a strategy to reduce disease symptoms and complications without substantially affecting viral replication or viral burden.
Can be used as a prophylactic treatment for individuals at risk (e.g., elderly, immunosuppressed) to prevent or reduce symptoms from infection-induced lung inflammation.
Administration of anti-S100A9 antibody reduces pro-inflammatory cytokines (TNF-α and IL-6) and apoptosis in the lung.
Documented Applications
Treatment of pathogen-induced lung inflammation in subjects, specifically targeting respiratory viruses such as Influenza virus (types A, B, C), Respiratory Syncytial Virus (RSV), Parainfluenza, Adenoviruses, Rhinoviruses, Human metapneumoviruses, and Coronaviruses including SARS-CoV-2 and COVID-19.
Prophylactic prevention or mitigation of lung inflammation in at-risk subjects, such as the elderly, obese, diabetics, cancer patients, sarcoid patients, and immunosuppressed subjects, prior to or upon exposure to respiratory pathogens.
Treatment or prophylaxis for inflammation-associated airway diseases such as pneumonia, bronchiolitis, COPD, and asthma.
Adjunct therapy in combination with antimicrobial (antiviral, antibiotic, or antifungal) drugs for the management of pathogen-induced lung diseases.
Reduction of RSV infection burden and reduction of pro-inflammatory cytokines following RSV infection.
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