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

• Type of Material: Article
• Authors: Laura Rodriguez, University of Rochester; Pilar Blanco-Lobo, University of Rochester; Emma C. Reilly, University of Rochester; Tatsuya Maehigashi, Emory University; Aitor Nogales, University of Rochester; Andrew Smith, University of Rochester; David J. Topham, University of Rochester; Stephen Dewhurst, University of Rochester; Baek Kim, Emory University; Luis Martinez-Sobrido, University of Rochester
• Language: English
• Date: 2019-10-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/v11100928
• Title of Journal or Parent Work: Viruses
• ISSN: 1999-4915
• Volume: 11
• Issue: 10
• Grant/Funding Information: This research was partially funded by the New York Influenza Center of Excellence (NYICE) (NIH 272201400005C), a member of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services, Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract No. HHSN272201400005C (NYICE); the Department of Defense (DoD) Peer Reviewed Medical Research Program (PRMRP) grant W81XWH-18-1-0460 to LMS; and NIH T32GM068411 and T32GM007356 (to AS).
• Keywords: ORIGIN; influenza; vaccine; SCHOOLCHILDREN; T-CELL RESPONSES; Virology; Life Sciences & Biomedicine; Science & Technology; live-attenuated vaccine; EFFICACY; HEMAGGLUTININ; SAFETY; GENES; PROTECTION; REPLICATION; A VIRUS
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

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.