Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses

doi:10.1126/science.aaz5143

GSTDTAP > 气候变化

DOI	10.1126/science.aaz5143
	Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses
	Nicholas C. Wu; Andrew J. Thompson; Juhye M. Lee; Wen Su; Britni M. Arlian; Jia Xie; Richard A. Lerner; Hui-Ling Yen; Jesse D. Bloom; Ian A. Wilson
	2020-06-19
发表期刊	Science
出版年	2020
英文摘要	Broadly neutralizing human antibodies (bnAbs) to the stem of hemagglutinin (HA), a trimeric glycoprotein found on the surface of influenza viruses, are valuable therapeutics and can guide the development of universal influenza vaccines. For their use in therapy development, it is important to understand the extent to which HA stem variants with resistance to bnAbs can develop. Wu et al. used saturation mutagenesis combined with next-generation sequencing to systematically search for resistance mutations to prototypic bnAbs in two influenza subtypes, H3 and H1. They found that the genetic barrier to resistance to stem bnAbs was low for the H3 subtype but higher for the H1 subtype. The ability of H3 to develop resistance to bnAbs presents a challenge in the development of a universal influenza vaccine. Science , this issue p. [1335][1] The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine. [1]: /lookup/doi/10.1126/science.aaz5143
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/276692
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Nicholas C. Wu,Andrew J. Thompson,Juhye M. Lee,et al. Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses[J]. Science,2020.
APA	Nicholas C. Wu.,Andrew J. Thompson.,Juhye M. Lee.,Wen Su.,Britni M. Arlian.,...&Ian A. Wilson.(2020).Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.Science.
MLA	Nicholas C. Wu,et al."Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses".Science (2020).