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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Endemic Poultry Viral Diseases Research » Research » Publications at this Location » Publication #388965

Research Project: Elucidation of Molecular Determinants of Avian Herpesviruses Virulence and Evolution to Inform the Development of Safe and Effective Vaccines

Location: Endemic Poultry Viral Diseases Research

Title: Coinfection in the host can result in functional complementation between live vaccines and virulent virus

Author
item XU, HUIA - University Of Illinois
item KRITER, ANDREA - University Of Illinois
item PONNURAJ, NAGENDRAPRABHU - University Of Illinois
item TIEN, YVETTE - University Of Illinois
item Kim, Taejoong
item JAROSINSKI, KEITH - University Of Illinois

Submitted to: Virulence
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/23/2022
Publication Date: 6/5/2022
Citation: Xu, H., Kriter, A.L., Ponnuraj, N., Tien, Y., Kim, T.N., Jarosinski, K.W. 2022. Coinfection in the host can result in functional complementation between live vaccines and virulent virus. Virulence. https://doi.org/10.1080/21505594.2022.2082645.
DOI: https://doi.org/10.1080/21505594.2022.2082645

Interpretive Summary: A vaccine is the most effective strategy to control viral diseases. Many different types of vaccines prevent viral disease, including the killed vaccine, live attenuated vaccine, and vectored vaccine. A low effective vaccine with the live virus can cause potential side effects with regain of virus virulence through mixed infection in a host. We report here the evidence that a viral protein from the herpesvirus vaccine can complement the compatible protein of wildtype virus. It is the first experimental evidence directly showing the complementation of specific protein between the vaccine and wildtype viruses. This event should be considered when designing new vaccine formulations in the future.

Technical Abstract: One of the greatest achievements of the last century is the development of vaccines against viral diseases. Vaccines are essential for battling infectious diseases and many different formulations are available, including live attenuated vectored vaccines. However, the use of live attenuated vaccines has the potential for adverse effects, including reversion of pathogenicity, recombination, and functional complementation in the host. Marek's disease is a serious disease in poultry controlled by live attenuated vaccines that has resulted in increased virulence over the decades. Recombination between circulating field viruses or vaccines is a proposed mechanism for the increase in virulence, but thus far there is little evidence to show this to occur in nature. Here, we describe a unique mechanism contributing to increased virulence, the result of complementation of vaccines with non-transmissible virulent virus to yield transmissible virulent virus. Using the natural virus-host model of Marek's disease in chickens, our results show dual infection of cells in chickens with vaccine and virulent virus providing the opportunity for recombination or complementation to transpire. Our results show no evidence of recombination between vaccine and virulent virus, but functional complementation occurred in two independent experiments providing proof for complementation during natural infection in vaccinated individuals. These results suggest complementation as a potential mechanism for vaccine-mediated viral evolution and the potential for complementation should be taken into consideration when developing novel vaccines.