Novel therapeutic monoclonal antibody targeting SP-R210 isoforms to prevent influenza disease progression and expedite resolution of comorbidities

Project: Research projectSmall Business Technology Transfer (STTR) Grants - Phase I

Description

Abstract: Respana Therapeutics? is focused on developing a proprietary monoclonal antibody (mAb) to address morbidities and mortality associated with both seasonal and pandemic influenza illness. The product will be an injectable mAb that calibrates the immune response to respiratory infection, attenuates injurious inflammation and expedites restoration of lung health after influenza A virus (IAV) infection. Our goal is to develop a safe, affordable, scalable and widely available product that can be used in conjunction with current anti-influenza medications to improve outcomes for influenza patients, reduce duration of symptoms, reduce post-influenza bacterial respiratory infections such as pneumonia or sinusitis, reduce hospitalizations and mortality, and strengthen the health care systems ability to combat seasonal and pandemic influenza. Respiratory influenza infection creates a widespread innate and adaptive immune system response that causes acute inflammation in the lung. This inflammatory response, while necessary to fighting the virus, can persist in the lung long after the offending virus is cleared and can lead to further morbidities, including secondary bacterial pneumonia, hospitalization due to serious lung injury, and ultimately death. Our innovative work on the surfactant protein (SP-A) receptor SP-R210 has shown that it increases phagocytosis of SP-A-bound pathogens and modulates cytokine secretion by immune cells. SP-A plays an important role in pulmonary immunity by enhancing opsonization and clearance of pathogens and by modulating macrophage inflammatory responses. Our data support a biological model in which SP-R210 isoforms differentially regulate trafficking, expression, and activation of innate immune receptors on macrophages. Proof of concept studies in vivo show that IAV infected mice, when treated with SP-R210 targeted mAbs, recover more quickly, have better post-infection lung function, and show better lung histopathology than untreated mice. Our specific objective for phase 1 is to show, in a dose-ranging, statistically powered animal study, that animals treated with SP-R210 mAbs recover faster from influenza infection, demonstrate improved lung function throughout the post-viral infection period and show reduced susceptibility to post-viral bacterial infection. A secondary objective is to assess the impact of SP-R210 antibodies on humoral and mucosal innate immunity.
StatusActive
Effective start/end date8/23/187/31/19

Funding

  • National Institutes of Health: $298,498.00

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Human Influenza
Disease Progression
Comorbidity
Protein Isoforms
Monoclonal Antibodies
Lung
Virus Diseases
Respiratory Tract Infections
Influenza A virus
Pandemics
Bacterial Infections
Therapeutics
Pneumonia
Hospitalization
Macrophages
Viruses
Morbidity
Bacterial Pneumonia
Biological Models
Mucosal Immunity