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

Pathogens

卷:9

Javier Ortego¹  Luis Martinez-Sobrido²  Kevin Chiem²  ThomasA. Hilimire²  Aitor Nogales² 

[1] Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid, Spain;

[2] Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA;

关键词: live attenuated influenza vaccine;    influenza;    master donor virus;    virus–host interaction;    vaccine safety;    immunogenicity;    protection efficacy;   

DOI  :  10.3390/pathogens9020086

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown