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Open AccessArticle

Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines

1
Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA
2
David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA
3
Center for Drug Discovery, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, GA 30322, USA
4
Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York, NY 14642, USA
5
College of Pharmacy, Kyung-Hee University, Seoul 02447, Korea
*
Author to whom correspondence should be addressed.
Current address: Agencia Española de Medicamentos y Productos Sanitarios, E-28022 Madrid, Spain.
Viruses 2019, 11(10), 928; https://doi.org/10.3390/v11100928
Received: 10 September 2019 / Revised: 3 October 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Section Antivirals & Vaccines)
Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (ts), cold-adapted (ca) and attenuated (att) phenotypes of the two MDVs have been previously identified and genetically mapped. However, a direct comparison of the contribution of these residues to viral attenuation, immunogenicity and protection efficacy has not been conducted. Here, we compared the In vitro and in vivo phenotype of recombinant influenza A/Puerto Rico/8/34 H1N1 (PR8) viruses containing the ts, ca and att mutations of the US (PR8/AA) and the Russian (PR8/Len) MDVs. Our results show that PR8/Len is more attenuated in vivo than PR8/AA, although both viruses induced similar levels of humoral and cellular responses, and protection against homologous and heterologous viral challenges. Our findings support the feasibility of using a different virus backbone as MDV for the development of improved LAIVs for the prevention of IAV infections. View Full-Text
Keywords: influenza; vaccine; live-attenuated vaccine influenza; vaccine; live-attenuated vaccine
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Rodriguez, L.; Blanco-Lobo, P.; Reilly, E.C.; Maehigashi, T.; Nogales, A.; Smith, A.; Topham, D.J.; Dewhurst, S.; Kim, B.; Martínez-Sobrido, L. Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines. Viruses 2019, 11, 928.

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