Disease burden due to influenza is significant. The 2009 H1N1 pandemic is unfolding as this proposal is being written. As of August 23, 2009, over 209,438 laboratory-confirmed cases of 2009 H1N1 influenza viruses with at least 2,185 deaths have been reported by the World Health Organization. Rapid, accurate, point-of-care detection kits that possess the capability to test for susceptibility of the virus to current antivirals are critical in our fight against this deadly virus. The objective of this proposal is to develop novel glycan based diagnostic platforms that target the viral glycoproteins, Hemagglutinin (HA) and Neuraminidase (NA), which are abundant (~50 copies of tetrameric NA and 300 copies of trimeric HA) on the surface of the virion. The rationale for this proposal is that a well designed glycan microarray platform will yield a "fingerprint pattern of recognition" on exposure to the virus. The novelty of this proposal is that susceptibility to Tamiflu(r) and Relenza(r), can be rapidly evaluated without the time consuming need to identify and characterize an emerging strain.
In Specific Aim 1, we will generate a library of glycans to capture and assess antiviral susceptibility of influenza.
In Specific Aim 2, we will develop different diagnostic platforms to capture and type influenza strains. We will also develop tests to determine sensitivity or resistance to antiviral agents. These tests are especially important since there is currently no method to rapidly detect and assess antiviral susceptibility before the genomic sequence for antiviral resistance mutations has been determined.
In Specific Aim 3, we will evaluate the different platforms using clinical samples. Specifically, we will examine the robustness, sensitivity, and selectivity of the diagnostic platforms using clinical samples isolated from infected patients and assess antiviral susceptibility. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise detection and differentiation of different influenza strains.

Public Health Relevance

An interdisciplinary team of scientists will develop glycan-based diagnostics for influenza virus. We will synthesize a library of glycans, incorporate these glycans into multiple diagnostic platforms and evaluate their performance to detect influenza and assess susceptibility to antivirals using clinical human samples. Successful completion of these specific aims is expected to lead to the development of rapid, robust, user friendly diagnostics for influenza virus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI089450-04
Application #
8509585
Study Section
Special Emphasis Panel (ZAI1-FDS-M (M2))
Program Officer
Krafft, Amy
Project Start
2010-05-15
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2013
Total Cost
$357,591
Indirect Cost
$117,407
Name
University of Cincinnati
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Yang, Yang; He, Yun; Li, Xingzhe et al. (2014) Bifunctional thiosialosides inhibit influenza virus. Bioorg Med Chem Lett 24:636-43
Dinh, Hieu; Zhang, Xiaohu; Sweeney, Joyce et al. (2014) Glycan based detection and drug susceptibility of influenza virus. Anal Chem 86:8238-44
Lee, Changwon; Gaston, Marsha A; Weiss, Alison A et al. (2013) Colorimetric viral detection based on sialic acid stabilized gold nanoparticles. Biosens Bioelectron 42:236-41