Brichacek, Allison
(2016)
Evaluation of a novel antiviral for influenza infection in the ferret model.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Influenza viruses, although common, cause thousands of deaths worldwide and remain a prominent public health issue, especially with the growing population of elderly and immune-compromised individuals. Currently, the influenza vaccine is the best tool available at protecting against infection, but the correct strains are hard to predict and the vaccines do not always work. Therefore, it is necessary to explore more effective antiviral drugs. New antivirals like these are of public health importance because they can help reduce morbidity and mortality related to influenza infection. Our collaborators from the University of Washington have computationally designed a small protein, HB36.6, which interferes with influenza infection by binding the virus’ hemagglutinin surface protein. This thesis has tested the novel antiviral using the influenza A/California/07/09 (H1N1) strain in a ferret model by looking at the effects of low and high doses of HB36.6, and comparing it to untreated controls or against the current standard antiviral, Tamiflu. Antiviral effectiveness was evaluated using a combination of clinical and viral parameters. First, the animals were monitored and scored using a detailed clinical scoring system for onset of clinical signs of disease, as well as tracked through daily measurements of weights and temperatures. Second, viral titers were quantitated using RT-PCR in tissue samples obtained at necropsy and the untreated controls were compared to HB36.6-treated animals or those treated with Tamiflu. The overall hypothesis for this study was that HB36.6 will be effective in reducing viral loads and limiting disease following aerosolized influenza infection in the ferret model, and this reduction in viral loads/disease would be more effective than the currently used antiviral, Tamiflu. The results of these studies show that HB36.6-treated animals display fewer clinical symptoms when a low dose of the treatment is used, but there appears to be no reduction in viral loads. Higher doses appear to be toxic to the animals, especially when taken over multiple days throughout the course of infection. These studies have yielded important information on a new class of influenza therapeutics that should be further evaluated using larger sample sizes.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
29 June 2016 |
| Date Type: |
Publication |
| Defense Date: |
7 April 2016 |
| Approval Date: |
29 June 2016 |
| Submission Date: |
28 April 2016 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
116 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
influenza, antivirals, ferrets |
| Date Deposited: |
29 Jun 2016 17:55 |
| Last Modified: |
01 May 2017 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/27886 |
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