Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Lulan Wang, Su-Yang Liu, Hsiang-Wen Chen, Juan Xu, Maxime Chapon, Tao Zhang, Fan Zhou, Yao E. Wang, Natalie Quanquin, Guiqin Wang, Xiaoli Tian, Zhanlong He, Longding Liu, Wenhai Yu, David Jesse Sanchez, Yuying Liang, Taijiao Jiang, Robert Modlin, Barry R. Bloom, Qihan Li, Jane C. Deng, Paul Zhou, F. Xiao-Feng Qin, Genhong Cheng
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.

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Teaser

Wang et al. use in vivo screening of a mutant influenza virus library to identify W7-791, an attenuated mutant strain. A single administration of W7-791 provided heterologous protection against lethal virus challenge in mice and ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection to naive animals.


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