Pre-clinical development of a mucosally-delivered flu antiviral

Focus: 

To conduct in vivo testing of a novel biologic that prevents and treats influenza

Anticipated Impact: 

A highly effective preventive and therapeutic agent for existing and novel flu strains

Abstract: 

Flu causes significant mortality, partly because available antivirals, such as Tamiflu, are only somewhat effective. Antivirals also have significant side effects. Using the computational platform Rosetta, a small protein that binds Group 1 flu viruses was designed and shown to be effective in preventing flu shortly before and after virus exposure in preliminary preclinical studies. The work plan includes determining appropriate dosing for H1N1, confirming protection from H5N1 and H9N2, and determining the ideal delivery method. This project was initially funded as a pilot project through an Opportunity grant to David Baker.  A startup company, Virvio, Inc., has been formed to commercialize the antiviral.

Collaborating organizations: University of Pittsburgh, Virvio

A supplement was awarded to perform more sophisticated analysis of the antiviral’s effect on inflammation when used as a prophylactic (protective) “vaccine” in a ferret animal model.  In addition, the antiviral’s effectiveness as a therapeutic in the ferret animal model will be tested.

Flu Prevention, Treatment

Grant Update

Principal Investigator:
Deborah Fuller
Grantee Organization:
University of Washington
Grant Title:
Pre-clinical development of a mucosally-delivered flu antiviral
Grant Cohort and Year:
2015 Proof of Concept (03)
Grant Period:
07/16/2015 - 07/15/2018 (Active)
Grant Amount:
$296,066
We have identified an optimum dose and regimen for our novel flu antiviral (HB36.6) that results in increased durability of protection with minimum number of doses. We demonstrated HB36.6 provides protection against a different (Group 1) influenza strains (i.e. H1N1 and H5N1) and affords superior protection from influenza when compared to Tamiflu. This work was published in PLoS Pathogens and featured in several news articles in Feb 2016. We successfully radio labeled HB36.6 to investigate biodistirbution and stability of HB36.6 in vivo. when administered as into the respiratory tract via droplet or mist and demonstrated that mist delivery resulted in greater biodistribution of the antiviral into the lung and longer bioavailability. This experiment was done in the preclinical ferret model for influenza infection and provides important insight into the best method to deliver the antiviral. We founded Virvio, Inc. to commercialize influenza binders as novel antivirals for flu. The company was awarded an STTR grant to develop mini flu binders with optimum potency, stability and that could be synthesized at lower cost. Virvio, Inc., in collaboration with IPD and UW successfully designed synthesizable mini binders. We identified an optimum minibinder and demonstrated it was superior to HB36.6 in neutralizing group 1 influenza strains in vitro and protection in mice in vivo.

Impact in Washington

Location of LSDF Grantee
Locations of Collaborations/Areas of Impact
Seattle

Legislative Districts:
11, 34, 36, 37, 43, 46

Health Impacts

Flu Prevention, Treatment

Feb 4, 2016
University of Washington Health Sciences NewsBeat