Abstract
Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines.
Highlights
Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease
Both inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) have been shown to be efficient for the treatment of influenza viral infections, there is an unmet need to increase the effectiveness of seasonal influenza vaccines
We discussed the use of reverse genetics for the generation of influenza vaccines with a special focus on LAIVs
Summary
Influenza A (IAV) and B (IBV) viruses belong to the Orthomyxoviridae family of enveloped viruses [1]. Infection with IAV or IBV induces a protective immunity mediated, at least partially, by antibodies directed against the viral HA, which is the main immunogenic target in both natural infections and vaccine approaches. Influenza NA glycoprotein is responsible for the cleavage of sialic acid moieties from sialyloligosaccharides and facilitates the release of newly produced virions from infected cells [17,18]. Two major lineages of IBV are circulating in humans, the Victoria-like and Yamagata-like subtypes that are divergent from the ancestral IBV (B/Lee/1940) and have been co-circulating in humans since the 1980s [5,21,22]. These two subtypes are the predominant circulating virus strains about once every three years [23,24,25]
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