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流感病毒HA-Stalk可推动突变病毒逃逸选择
作者:小柯机器人 发布时间:2020/6/30 21:06:32

美国国立卫生研究院Jeffery K. Taubenberger研究组取得最新进展。他们发现对流感病毒血凝素(HA)茎的既存免疫力,可能会推动人类挑战模型中抗体诱导的突变病毒逃逸的选择。该研究于2020年6月29日发表于《自然-医学》。

他们表明,在受到2009年H1N1大流行性流感病毒接种物(在HA茎中含有A388V多态性)(45%野生型和55%突变体)挑战的研究参与者中,HA茎上的免疫压力可以导致逃逸突变病毒的扩增。高水平的茎抗体滴度与人类和体外突变病毒的选择有关。尽管突变病毒在小鼠中显示出轻微复制减少,但在细胞培养、雪貂或人类挑战参与者中未观察到。

A388V突变赋予了对一些有效的HA茎的抵抗力,这些茎广泛地中和了单克隆抗体(bNAbs)。在bNAb或人血清中共培养野生型和突变型病毒会导致突变体快速扩增。这些数据揭示了靶向HA茎的通用流感疫苗,成功地克服了潜在障碍-疫苗诱导的茎免疫的病毒逃逸。

据了解,保守的流感HA茎(或茎)区域已受到关注,成为通用流感疫苗的有效靶标。尽管HA茎杆区域的保存相对较好,但是流感病毒的进化动态特性,引起了人们对在足够的免疫压力下携带茎杆逃逸突变的病毒可能出现的担忧。

附:英文原文

Title: Pre-existing immunity to influenza virus hemagglutinin stalk might drive selection for antibody-escape mutant viruses in a human challenge model

Author: Jae-Keun Park, Yongli Xiao, Mitchell D. Ramuta, Luz Angela Rosas, Sharon Fong, Alexis M. Matthews, Ashley D. Freeman, Monica A. Gouzoulis, Natalia A. Batchenkova, Xingdong Yang, Kelsey Scherler, Li Qi, Susan Reed, Rani Athota, Lindsay Czajkowski, Alison Han, David M. Morens, Kathie-Anne Walters, Matthew J. Memoli, John C. Kash, Jeffery K. Taubenberger

Issue&Volume: 2020-06-29

Abstract: The conserved region of influenza hemagglutinin (HA) stalk (or stem) has gained attention as a potent target for universal influenza vaccines1,2,3,4,5. Although the HA stalk region is relatively well conserved, the evolutionarily dynamic nature of influenza viruses6 raises concerns about the possible emergence of viruses carrying stalk escape mutation(s) under sufficient immune pressure. Here we show that immune pressure on the HA stalk can lead to expansion of escape mutant viruses in study participants challenged with a 2009 H1N1 pandemic influenza virus inoculum containing an A388V polymorphism in the HA stalk (45% wild type and 55% mutant). High level of stalk antibody titers was associated with the selection of the mutant virus both in humans and in vitro. Although the mutant virus showed slightly decreased replication in mice, it was not observed in cell culture, ferrets or human challenge participants. The A388V mutation conferred resistance to some of the potent HA stalk broadly neutralizing monoclonal antibodies (bNAbs). Co-culture of wild-type and mutant viruses in the presence of either a bNAb or human serum resulted in rapid expansion of the mutant. These data shed light on a potential obstacle for the success of HA-stalk-targeting universal influenza vaccines—viral escape from vaccine-induced stalk immunity.

DOI: 10.1038/s41591-020-0937-x

Source: https://www.nature.com/articles/s41591-020-0937-x

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex