Format

Send to

Choose Destination
Version 2. F1000Res. 2019 Nov 6 [revised 2020 Feb 21];8:1860. doi: 10.12688/f1000research.21082.2. eCollection 2019.

Delayed administration of recombinant plasma gelsolin improves survival in a murine model of severe influenza.

Author information

1
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
2
BioAegis Therapeutics, North Brunswick, NJ, 07960, USA.

Abstract

Background: Host-derived inflammatory responses contribute to the morbidity and mortality of severe influenza, suggesting that immunomodulatory therapy may improve outcomes. The normally circulating protein, human plasma gelsolin, is available in recombinant form (rhu-pGSN) and has beneficial effects in a variety of pre-clinical models of inflammation and injury.   Methods: We evaluated delayed therapy with subcutaneous rhu-pGSN initiated 3 to 6 days after intra-nasal viral challenge in a mouse model of influenza A/PR/8/34. Results: Rhu-pGSN administered starting on day 3 or day 6 increased survival (12-day survival: 62 % vs 39 %, pGSN vs vehicle; p < 0.00001, summary of 18 trials), reduced morbidity, and decreased pro-inflammatory gene expression. Conclusions: Rhu-pGSN improves outcomes in a highly lethal influenza model when given after a clinically relevant delay.

KEYWORDS:

host-directed; immunomodulation; influenza; plasma gelsolin; pneumonia

Conflict of interest statement

Competing interests: S. Levinson and M. DiNubile are employees and shareholders of BioAegis Therapeutics. T. Stossel is a founder, shareholder and consultant to BioAegis Therapeutics.

Supplemental Content

Full text links

Icon for F1000 Research Ltd Icon for PubMed Central
Loading ...
Support Center