A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.
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DOI:
10.1016/j.vaccine.2011.06.015
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发表时间:
2011-08-05
期刊:
影响因子:
5.5
通讯作者:
Broder, Christopher C.
Broder, Christopher C.
中科院分区:
医学3区
文献类型:
--
作者:
Pallister, Jackie;Middleton, Deborah;Wang, Lin-Fa;Klein, Reuben;Haining, Jessica;Robinson, Rachel;Yamada, Manabu;White, John;Payne, Jean;Feng, Yan-Ru;Chan, Yee-Peng;Broder, Christopher C.

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亨德拉病毒(Hendra virus,HeV)和尼帕病毒(Nipah virus,NiV)是两种致命的人畜共患病毒,目前还没有疫苗或治疗药物被批准用于人类或牲畜。自1994年以来,在14次疫情中,HeV导致了马和人类的多起死亡事件,所有已知的人类感染都是由于与受感染的马密切接触造成的。一种防止病毒在受感染的马匹中脱落的疫苗可以中断向人类的传播链,从而防止两者的HeV疾病。在这里,我们研究了雪貂模型中的HeV感染,并表明它密切反映了人类和马中所见的疾病,诱导系统性血管炎,包括肺部和中枢神经系统的参与。该雪貂中的HeV感染模型用于评估基于用CpG佐剂的重组可溶性形式的HeV附着糖蛋白G(HeVsG)的亚单位疫苗的免疫原性和保护效力。我们报告了用100 μg、20 μg或4 μg剂量的HeVsG接种的雪貂在用5,000 TCID50的HeV攻击后仍然没有HeV感染的临床体征。此外,相当重要的是,在100 μ g和20 μg组的任何雪貂的任何组织或体液中均未检测到病毒或病毒基因组的证据,而在4 μg组中仅在一只动物的鼻洗液中检测到基因组。总之,我们的研究结果表明,100 μg或20 μg剂量的HeVsG疫苗可以完全预防雪貂中的生产性HeV感染,这表明接种疫苗以预防HeV的感染和脱落是可能的。
The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5,000 TCID50 of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible.
DOI: 10.1128/jvi.01847-09
发表时间: 2009-11-15
影响因子: 5.4
作者:
Pallister, Jackie;Middleton, Deborah;Wang, Lin-Fa
通讯作者: Wang, Lin-Fa
DOI: 10.1053/jcpa.2001.0532
发表时间: 2002-02-01
影响因子: 0.8
作者:
Middleton, DJ;Westbury, HA;Hyatt, AD
通讯作者: Hyatt, AD
DOI: 10.1128/jvi.02022-06
发表时间: 2007-06-01
影响因子: 5.4
作者:
Bishop, Kimberly A.;Stantchev, Tzanko S.;Broder, Christopher C.
通讯作者: Broder, Christopher C.
DOI: 10.1126/science.7701348
发表时间: 1995-04-07
期刊: SCIENCE
影响因子: 56.9
作者:
MURRAY, K;SELLECK, P;KETTERER, P
通讯作者: KETTERER, P
DOI: 10.1016/s0764-4469(00)87191-7
发表时间: 1999-11-01
期刊: COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES
影响因子: --
作者:
Plotkin, SA
通讯作者: Plotkin, SA