BackgroundVaccines have been effective, but… Simply put, vaccines are preparations that, when introduced to the body, trigger an immune response and prepare the body’s natural defences against attack from a specific pathogen. They have been used to great effect in the poultry industry to prevent, or reduce the impact of, a number of economically important diseases. …there is room for improvement However, vaccines are not without their drawbacks. For example, although “live vaccines” prepared from live bacteria or viruses are generally effective at protecting from subsequent invasion of the same (or similar) pathogen, they can sometimes cause symptoms of the disease against which they were designed to protect. There is also growing concern that certain live vaccine viruses have the ability to revert back to virulent, disease-causing forms, or even recombine (exchange genetic material) with wild viral strains thereby creating new strains with potentially unpredictable traits. While killed viral vaccines eliminate much of the risk associated with some live vaccines, they are generally less effective.
OutcomesEngineering a solution As more is learned about pathogens and the host’s immune responses to them, new vaccine types are emerging that overcome the shortcomings of their predecessors and incorporate features that improve their effectiveness and utility. For example, scientists have identified specific viral proteins that elicit an immune response. Inoculating with these immunogenic proteins, or “antigens”, eliminates the need for, and associated risks of, using intact virus. The challenge is to find an effective way to deliver these antigens to the body. Dr. Éva Nagy and her research group at the University of Guelph are using the molecular machinery from a strain of fowl adenovirus (FAdV; a strain that does not cause disease in poultry) as a “genetic delivery system”. Explanation of the delivery system first requires brief description of viruses in general: Virus particles are extremely small and, compared to a cell, are quite simple. In the case of adenoviruses, they consist only of a set of genetic instructions (DNA) and a coat of protein that protects the DNA. Viruses do not have the chemical machinery necessary to reproduce themselves and thus must have a host cell in which to live and make more viruses. Since their propagation depends on it, adenoviruses are very good at getting their DNA into a host cell. This trait is exploited in Dr. Nagy’s delivery system. The researchers identified portions of the FAdV genome that are not necessary to produce intact virus and, using modern techniques of molecular biology, replaced some of these sequences with genes coding for specific antigens. The resulting virus vector retains its ability to infect cells, but its genetic payload now also instructs the host cell to produce the antigens that will elicit the desired immune response in the host. Dr. Nagy was successful in inserting genes coding for antigens from both Avian Influenza and Newcastle Disease viruses. When used as a vaccine, the vector should simultaneously protect birds from both diseases. Experiments to test this ability are in preparation. While engineering a FAdV-based vector is not trivial, Dr. Nagy’s success illustrates the power and flexibility of the system. Using the same biological platform, a wide array of antigens can be produced. Antigens and proteins that enhance the bird’s immune response to them could be delivered simultaneously. These vaccines can also be engineered to allow distinction between birds that were vaccinated and those that were naturally infected by intact virus. This technology is formally known as ”Differentiation of naturally Infected from Vaccinated Animals (DIVA) and will be an important component of many commercially viable vaccination strategies in the future.
Funding$276,750 (CPRC $96,750, NSERC/AAFC $180,000)
PublicationsCorredor, J.C. and Nagy, É. 2010. The non-essential left end region of the fowl adenovirus 9 genome is suitable for foreign gene insertion/replacement. Virus Research, 149;167-174. Epub 2010 Feb 2. Corredor, J.C. and Nagy, É. 2010. A region at the left end of the fowl adenovirus 9 genome that is non-essential in vitro has consequences in vivo. Journal of General Virology, 91(Pt 1):51-58. Epub 2009 Sep 16. Romanova, N., Corredor, J.C. and Nagy, É. 2009. Detection and quantitation of fowl adenovirus genome by a real-time PCR assay. Journal of Virological Methods, 159:58-63.