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改良安卡拉痘苗病毒表达的大流行(H1N1)2009 病毒血凝素诱导小鼠对欧亚“禽源样”H1N1 猪病毒产生交叉保护免疫。

Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice.

机构信息

Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Influenza Other Respir Viruses. 2014 May;8(3):367-75. doi: 10.1111/irv.12221. Epub 2013 Dec 23.

Abstract

OBJECTIVES

To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs.

DESIGN

Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice.

SAMPLE

Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study.

SETTING

Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses.

MAIN OUTCOME MEASURES

Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge.

RESULTS AND CONCLUSIONS

Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans.

摘要

目的

研究血凝素(HA)来源于 A/加利福尼亚/7/09(CA/09)病毒与 1999 年至 2008 年期间在意大利进行猪的病毒学监测时分离的代表欧亚“禽样”(EA)H1N1 猪病毒之间的交叉反应性。

设计

使用表达 CA/09 病毒 HA 基因的改良安卡拉痘苗病毒(MVA)(MVA-HA-CA/09)作为疫苗,在小鼠中研究针对 H1N1 猪病毒的交叉保护免疫。

样本

本研究使用了两种经典的猪 H1N1(CS)病毒和之前在意大利北部农场爆发猪呼吸道疾病期间分离的四种代表 EA 样 H1N1 猪病毒。

设置

雌性 C57BL/6 小鼠用 MVA/HA/CA/09 疫苗接种,然后用 H1N1 猪病毒滴鼻感染。

主要观察指标

通过血凝抑制(HI)和微量中和(MN)试验测定 MVA 疫苗接种小鼠血清中的交叉反应性抗体反应。通过测量攻毒后第 2 天和第 4 天肺部病毒载量来确定对 H1N1 猪病毒感染的保护程度。

结果与结论

用 MVA 载体的 CA/09 衍生 HA 对小鼠进行全身免疫,可诱导针对近期 EA 样猪病毒的交叉保护免疫。这种免疫保护与免疫小鼠血清中的交叉 HI 抗体水平有关,并且依赖于 H1 HA 的抗原位点 Sa 的相似性。我们的研究结果表明,大流行(H1N1)2009 病毒在人群中引起的群体免疫可能限制了最近的 EA 样猪 HA 基因在人类流感 A 病毒基因库中的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3175/4181486/4d0354326379/irv0008-0367-f1.jpg

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