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2009年大流行期间血凝素茎部反应性抗体与甲型H1N1流感病毒感染之间的关联

Association between Hemagglutinin Stem-Reactive Antibodies and Influenza A/H1N1 Virus Infection during the 2009 Pandemic.

作者信息

Hoa Le Nguyen Minh, Mai Le Quynh, Bryant Juliet E, Thai Pham Quang, Hang Nguyen Le Khanh, Yen Nguyen Thi Thu, Duong Tran Nhu, Thoang Dang Dinh, Horby Peter, Werheim Heiman F L, Fox Annette

机构信息

Oxford University Clinical Research Unit and Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.

National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.

出版信息

J Virol. 2016 Jun 24;90(14):6549-6556. doi: 10.1128/JVI.00093-16. Print 2016 Jul 15.

Abstract

UNLABELLED

The discovery of influenza virus broadly neutralizing (BrN) antibodies prompted efforts to develop universal vaccines. Influenza virus stem-reactive (SR) broadly neutralizing antibodies have been detected by screening antibody phage display libraries. However, studies of SR BrN antibodies in human serum, and their association with natural infection, are limited. To address this, pre- and postpandemic sera from a prospective community cohort study in Vietnam were assessed for antibodies that inhibit SR BrN monoclonal antibody (MAb) (C179) binding to H1N1 pandemic 2009 virus (H1N1pdm09). Of 270 households, 33 with at least one confirmed H1N1pdm09 illness or at least two seroconverters were included. The included households comprised 71 infected and 41 noninfected participants. Sera were tested as 2-fold dilutions between 1:5 and 1:40. Fifty percent C179 inhibition (IC50) titers did not exceed 10, although both IC50 titers and percent C179 inhibition by sera diluted 1:5 or 1:10 correlated with hemagglutination inhibition (HI) and microneutralization (MN) titers (all P < 0.001). Thirteen (12%) participants had detectable prepandemic IC50 titers, but only one reached a titer of 10. This proportion increased to 44% after the pandemic, when 39 participants had a titer of 10, and 67% of infected compared to 44% of noninfected had detectable IC50 titers (P < 0.001). The low levels of SR antibodies in prepandemic sera were not associated with subsequent H1N1pdm09 infection (P = 0.241), and the higher levels induced by H1N1pdm09 infection returned to prepandemic levels within 2 years. The findings indicate that natural infection induces only low titers of SR antibodies that are not sustained.

IMPORTANCE

Universal influenza vaccines could have substantial health and economic benefits. The focus of universal vaccine research has been to induce antibodies that prevent infection by diverse influenza virus strains. These so-called broadly neutralizing antibodies are readily detected in mice and ferrets after infection with a series of distinct influenza virus strains. The 2009 H1N1 pandemic provided an opportunity to investigate whether infection with a novel strain induced broadly neutralizing antibodies in humans. We found that broadly neutralizing antibodies were induced, but levels were low and poorly maintained. This could represent an obstacle for universal vaccine development and warrants further investigation.

摘要

未标注

流感病毒广泛中和(BrN)抗体的发现推动了通用疫苗的研发。通过筛选抗体噬菌体展示文库已检测到流感病毒茎反应性(SR)广泛中和抗体。然而,关于人血清中SR BrN抗体及其与自然感染的关联的研究有限。为解决这一问题,对越南一项前瞻性社区队列研究中的大流行前和大流行后血清进行了评估,以检测抑制SR BrN单克隆抗体(MAb)(C179)与2009年甲型H1N1流感病毒(H1N1pdm09)结合的抗体。在270户家庭中,纳入了33户至少有一例确诊H1N1pdm09疾病或至少有两名血清转化者的家庭。纳入的家庭包括71名感染者和41名未感染者。血清以1:5至1:40之间的2倍稀释度进行检测。50% C179抑制(IC50)滴度不超过10,尽管1:5或1:10稀释的血清的IC50滴度和C179抑制百分比与血凝抑制(HI)和微量中和(MN)滴度相关(所有P < 0.001)。13名(12%)参与者的大流行前IC50滴度可检测到,但只有1人达到10的滴度。大流行后这一比例增至44%,当时有39名参与者的滴度为10,且感染组中有67%的人IC50滴度可检测到,而未感染组为44%(P < 0.001)。大流行前血清中SR抗体水平较低与随后的H1N1pdm09感染无关(P = 0.241),且H1N1pdm09感染诱导产生的较高水平在2年内恢复到大流行前水平。这些发现表明,自然感染仅诱导产生低滴度且无法持续的SR抗体。

重要性

通用流感疫苗可能带来巨大的健康和经济效益。通用疫苗研究的重点一直是诱导能预防多种流感病毒株感染的抗体。这些所谓的广泛中和抗体在感染一系列不同流感病毒株后的小鼠和雪貂中很容易检测到。2009年甲型H1N1流感大流行提供了一个机会来研究感染一种新型毒株是否会在人类中诱导产生广泛中和抗体。我们发现确实诱导产生了广泛中和抗体,但水平较低且维持不佳。这可能是通用疫苗研发的一个障碍,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d628/4936154/04f0d7d80fff/zjv9991817840001.jpg

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