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单剂量全灭活H7N9流感疫苗可使雪貂免受重症疾病侵害,但不能防止其感染。

A single dose of whole inactivated H7N9 influenza vaccine confers protection from severe disease but not infection in ferrets.

作者信息

Wong Sook-San, Jeevan Trushar, Kercher Lisa, Yoon Sun-Woo, Petkova Atanaska-Marinova, Crumpton Jeri-Carol, Franks John, Debeauchamp Jennifer, Rubrum Adam, Seiler Patrick, Krauss Scott, Webster Robert, Webby Richard J

机构信息

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.

Animal Resource Center, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.

出版信息

Vaccine. 2014 Jul 31;32(35):4571-4577. doi: 10.1016/j.vaccine.2014.06.016. Epub 2014 Jun 18.

Abstract

The H7N9 influenza virus caused significant mortality and morbidity in infected humans during an outbreak in China in 2013 stimulating vaccine development efforts. As previous H7-based vaccines have been poorly immunogenic in humans we sought to determine the immunogenic and protective properties of an inactivated whole virus vaccine derived from a 2013 H7N9 virus in ferrets. As whole virus vaccine preparations have been shown to be more immunogenic in humans, but less likely to be used, than split or surface antigen formulations, we vaccinated ferrets with a single dose of 15, 30, or 50 μg of the vaccine and subsequently challenged with wild-type A/Anhui/1/2013 (H7N9) either by direct instillation or by contact with infected animals. Although ferrets vaccinated with higher doses of vaccine had higher serum hemagglutinin inhibition (HI) titers, the titers were still low. During subsequent instillation challenge, however, ferrets vaccinated with 50 μg of vaccine showed no illness and shed significantly less virus than mock vaccinated controls. All vaccinated ferrets had lower virus loads in their lungs as compared to controls. In a separate study where unvaccinated-infected ferrets were placed in the same cage with vaccinated-uninfected ferrets, vaccination did not prevent infection in the contact ferrets, although they showed a trend of lower viral load. Overall, we conclude that inactivated whole-virus H7N9 vaccine was able to reduce the severity of infection and viral load, despite the lack of hemagglutinin-inhibiting antibodies.

摘要

2013年中国爆发疫情期间,H7N9流感病毒在感染人类后导致了显著的死亡率和发病率,这推动了疫苗研发工作。由于之前基于H7的疫苗在人类中的免疫原性较差,我们试图确定一种源自2013年H7N9病毒的灭活全病毒疫苗在雪貂体内的免疫原性和保护特性。由于全病毒疫苗制剂在人类中已被证明比裂解或表面抗原制剂具有更强的免疫原性,但使用可能性较小,我们给雪貂接种了单剂量15微克、30微克或50微克的疫苗,随后通过直接滴注或与感染动物接触的方式用野生型A/安徽/1/2013(H7N9)进行攻毒。尽管接种较高剂量疫苗的雪貂血清血凝素抑制(HI)效价更高,但效价仍然较低。然而,在随后的滴注攻毒过程中,接种50微克疫苗的雪貂没有出现病症,并且病毒排出量明显低于 mock 接种对照。与对照组相比,所有接种疫苗的雪貂肺部的病毒载量都更低。在另一项研究中,将未接种疫苗的感染雪貂与接种疫苗的未感染雪貂放在同一个笼子里,尽管接触雪貂的病毒载量有降低趋势,但接种疫苗并不能预防感染。总体而言,我们得出结论,尽管缺乏血凝素抑制抗体,但灭活全病毒H7N9疫苗能够降低感染的严重程度和病毒载量。

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