| Literature DB >> 28279345 |
Lulan Wang1, Su-Yang Liu2, Hsiang-Wen Chen3, Juan Xu4, Maxime Chapon2, Tao Zhang4, Fan Zhou5, Yao E Wang2, Natalie Quanquin2, Guiqin Wang5, Xiaoli Tian6, Zhanlong He7, Longding Liu7, Wenhai Yu7, David Jesse Sanchez8, Yuying Liang9, Taijiao Jiang4, Robert Modlin10, Barry R Bloom11, Qihan Li7, Jane C Deng6, Paul Zhou5, F Xiao-Feng Qin12, Genhong Cheng13.
Abstract
New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.Entities:
Keywords: flu vaccine; genome-wide mutagenesis; influenza vaccine; matrix protein
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Year: 2017 PMID： 28279345 DOI： 10.1016/j.chom.2017.02.007
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023