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The role of influenza virus polymerase stability in vaccine safety
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Journal of AIDS & Clinical Research

ISSN: 2155-6113

Open Access

The role of influenza virus polymerase stability in vaccine safety




Andrew Cox

: J Antivir Antiretrovir

Abstract :

I nfluenza viruses infect millions of persons each year and are directly responsible for between 3,000 and 49,000 deaths annually in the United States. This morbidity and mortality has led to vaccination efforts against influenza A and B. Due to the low effectiveness of the triple inactivated virus (TIV), a live attenuated influenza virus (LAIV) was successfully developed to increased efficacy. The current LAIV has been increasing in popularity amongst health care providers due to both its less challenging route of administration and greater protection in persons age 1-49 1 and has recently been recommended as the primary vaccination strategy in this age group. Therefore, the mechanism underlying the stability of this attenuation is of great importance and not fully understood. This virus has been attenuated through cold adaptation and subsequent work has determined the attenuating segments. These are contained in the polymerase (PB1, PB2, PA) and nucleoprotein segments. It has been shown through viral recombination that while the introduction of the attenuating PB2 segment into a wild type background could convey temperature sensitivity, rescue mutations in PA could restore the ability to grow at elevated temperatures 2 . These revertant viruses are of great interest as they provide an insight into the mechanism of attenuation by providing genetically similar viruses with vastly differing phenotypes and are medically significant as they provide an insight into vaccine safety. We were gifted with these viral isolates from the lab of John Treanor and have isolated plaque purified viruses possessing impaired growth at 39°C as well as genetically similar revertant viruses who do not display reduced growth at 39°C. Further characterization of the responsible mechanism will include fully sequencing the viral genome of both the background and revertant isolates, performing a minigenome assay to determine polymerase function at various temperatures and biochemical analysis of trimeric stability in vitro.

Biography :

Andrew completed his bachelors in Biology/Chemistry from Southern Nazarene University in 2009 and is currently a MD/PhD student at the University of Rochester in the lab of Dr. Baek Kim working on the mechanism of vaccine attenuation present in the live attenuated influenza vaccine

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