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Open AccessArticle

Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine

1
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
2
Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Texas Biomedical Research Institute, 8715 W. Military Dr., San Antonio, TX 78212, USA.
Pathogens 2020, 9(2), 86; https://doi.org/10.3390/pathogens9020086
Received: 16 September 2019 / Revised: 18 January 2020 / Accepted: 22 January 2020 / Published: 29 January 2020
(This article belongs to the Special Issue Influenza Virus and Vaccination)
Seasonal influenza epidemics remain one of the largest public health burdens nowadays. The best and most effective strategy to date in preventing influenza infection is a worldwide vaccination campaign. Currently, two vaccines are available to the public for the treatment of influenza infection, the chemically Inactivated Influenza Vaccine (IIV) and the Live Attenuated Influenza Vaccine (LAIV). However, the LAIV is not recommended for parts of the population, such as children under the age of two, immunocompromised individuals, the elderly, and pregnant adults. In order to improve the safety of the LAIV and make it available to more of the population, we sought to further attenuate the LAIV. In this study, we demonstrate that the influenza A virus (IAV) master donor virus (MDV) A/Ann Arbor/6/60 H2N2 LAIV can inhibit host gene expression using both the PA-X and NS1 proteins. Furthermore, we show that by removing PA-X, we can limit the replication of the MDV LAIV in a mouse model, while maintaining full protective efficacy. This work demonstrates a broadly applicable strategy of tuning the amount of host antiviral responses induced by the IAV MDV for the development of newer and safer LAIVs. Moreover, our results also demonstrate, for the first time, the feasibility of genetically manipulating the backbone of the IAV MDV to improve the efficacy of the current IAV LAIV.
Keywords: live attenuated influenza vaccine; influenza; master donor virus; virus–host interaction; vaccine safety; immunogenicity; protection efficacy live attenuated influenza vaccine; influenza; master donor virus; virus–host interaction; vaccine safety; immunogenicity; protection efficacy
MDPI and ACS Style

Hilimire, T.A.; Nogales, A.; Chiem, K.; Ortego, J.; Martinez-Sobrido, L. Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine. Pathogens 2020, 9, 86.

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