Towards a universal vaccine for avian influenza: protective efficacy of modified Vaccinia virus Ankara and Adenovirus vaccines expressing conserved influenza antigens in chickens challenged with low pathogenic avian influenza virus.

Towards a universal vaccine for avian influenza: protective efficacy of modified Vaccinia virus Ankara and Adenovirus vaccines expressing conserved influenza antigens in chickens challenged with low pathogenic avian influenza virus.
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DOI:
10.1016/j.vaccine.2012.11.047
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发表时间:
2013-01-11
期刊:
影响因子:
5.5
通讯作者:
Butter, Colin
Butter, Colin
中科院分区:
医学3区
文献类型:
--
作者:
Boyd, Amy C.;Ruiz-Hernandez, Raul;Peroval, Marylene Y.;Carson, Connor;Balkissoon, Devanand;Staines, Karen;Turner, Alison V.;Hill, Adrian V. S.;Gilbert, Sarah C.;Butter, Colin

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►目前的流感疫苗不能产生异种保护作用。针对内部流感抗原的►可能提供交叉保护。我们在鸡体内检测了腺病毒和携带NP和M1的►。►异源Prime-Boost可使病毒提前停止脱落。目前针对表面蛋白的疫苗可以推动抗原变异,导致出现更高致病性的病毒或抗原上不同的病毒,这些病毒通过疫苗接种而逃脱控制,从而在宿主人口中持续存在。流感疫苗通常针对高度可变的表面蛋白,并不提供针对异源挑战的保护。诱导针对保守的流感表位的免疫反应的疫苗可能提供针对异源挑战的保护。本文报道了重组改良型痘苗病毒Ankara(MVA)和腺病毒(Ad)表达核蛋白和基质蛋白融合结构(NP+MM1)的免疫效果。在不同日龄的鸡身上试验了初级和强化免疫方案,发现它们是安全的和具有免疫原性的。用干扰素-γ(干扰素-γ)ELISpot检测二次免疫后的细胞免疫应答。在一个近交系和两个近交系中,在一个近交系和两个近交系中,对一个近交系和两个近交系来说,在孵化后4周进行MVA增强是最具免疫原性的方案。接种疫苗后,一个近交系(C15I)感染了低致病性禽流感H7N7(A/土耳其/英格兰/1977)。在感染后7天,与接种含有无关抗原的重组病毒的雏鸡相比,接受一次Ad-NP 10+MM1和二次接种MVA-NP 10+BM1的禽鸟的泄殖腔脱落明显减少。这一疗效的初步迹象证明了在禽类中的概念;通过含有内部流感抗原的病毒载体在鸡中诱导T细胞反应可能是开发疫苗以诱导家禽对流感的异源保护的一种有效策略。
► Current influenza vaccines do not generate heterologous protection. ► Targeting internal influenza antigens may confer cross protection. ► We tested Adenovirus and MVA vectored NP and M1 in chickens. ► Heterologous prime-boost resulted in earlier cessation of viral shedding. Current vaccines targeting surface proteins can drive antigenic variation resulting either in the emergence of more highly pathogenic viruses or of antigenically distinct viruses that escape control by vaccination and thereby persist in the host population. Influenza vaccines typically target the highly mutable surface proteins and do not provide protection against heterologous challenge. Vaccines which induce immune responses against conserved influenza epitopes may confer protection against heterologous challenge. We report here the results of vaccination with recombinant modified Vaccinia virus Ankara (MVA) and Adenovirus (Ad) expressing a fusion construct of nucleoprotein and matrix protein (NP + M1). Prime and boost vaccination regimes were trialled in different ages of chicken and were found to be safe and immunogenic. Interferon-γ (IFN-γ) ELISpot was used to assess the cellular immune response post secondary vaccination. In ovo Ad prime followed by a 4 week post hatch MVA boost was identified as the most immunogenic regime in one outbred and two inbred lines of chicken. Following vaccination, one inbred line (C15I) was challenged with low pathogenic avian influenza (LPAI) H7N7 (A/Turkey/England/1977). Birds receiving a primary vaccination with Ad-NP + M1 and a secondary vaccination with MVA-NP + M1 exhibited reduced cloacal shedding as measured by plaque assay at 7 days post infection compared with birds vaccinated with recombinant viruses containing irrelevant antigen. This preliminary indication of efficacy demonstrates proof of concept in birds; induction of T cell responses in chickens by viral vectors containing internal influenza antigens may be a productive strategy for the development of vaccines to induce heterologous protection against influenza in poultry.
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发表时间: 2012
期刊: PloS one
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期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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发表时间: 1968-01-01
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