表达血凝素基因的重组改良安卡拉痘病毒可使猕猴免受同源和异源H5N1流感病毒感染。

Recombinant modified vaccinia virus Ankara expressing the hemagglutinin gene confers protection against homologous and heterologous H5N1 influenza virus infections in macaques.

作者信息

Kreijtz J H C M, Suezer Y, de Mutsert G, van den Brand J M A, van Amerongen G, Schnierle B S, Kuiken T, Fouchier R A M, Löwer J, Osterhaus A D M E, Sutter G, Rimmelzwaan G F

机构信息

Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands.

出版信息

J Infect Dis. 2009 Feb 1;199(3):405-13. doi: 10.1086/595984.

Abstract

BACKGROUND

Highly pathogenic avian influenza viruses of the H5N1 subtype have been responsible for an increasing number of infections in humans since 2003. More than 60% of infected individuals die, and new infections are reported frequently. In light of the pandemic threat caused by these events, the rapid availability of safe and effective vaccines is desirable. Modified vaccinia virus Ankara (MVA) expressing the hemagglutinin (HA) gene of H5N1 viruses is a promising candidate vaccine that induced protective immunity against infection with homologous and heterologous H5N1 influenza virus in mice.

METHODS

In the present study, we evaluated a recombinant MVA vector expressing the HA gene of H5N1 influenza virus A/Vietnam/1194/04 (MVA-HA-VN/04) in nonhuman primates. Cynomolgus macaques were immunized twice and then were challenged with influenza virus A/Vietnam/1194/04 (clade 1) or A/Indonesia/5/05 (clade 2.1) to assess the level of protective immunity.

RESULTS

Immunization with MVA-HA-VN/04 induced (cross-reactive) antibodies and prevented virus replication in the upper and lower respiratory tract and the development of severe necrotizing bronchointerstitial pneumonia.

CONCLUSION

Therefore, MVA-HA-VN/04 is a promising vaccine candidate for the induction of protective immunity against highly pathogenic H5N1 avian influenza viruses in humans.

摘要

背景

自2003年以来,H5N1亚型高致病性禽流感病毒导致人类感染的病例不断增加。超过60%的感染者死亡,且新感染病例频繁报道。鉴于这些事件所造成的大流行威胁,安全有效的疫苗能够快速供应十分必要。表达H5N1病毒血凝素(HA)基因的改良安卡拉痘苗病毒(MVA)是一种有前景的候选疫苗,可在小鼠中诱导针对同源和异源H5N1流感病毒感染的保护性免疫。

方法

在本研究中,我们在非人灵长类动物中评估了一种表达H5N1流感病毒A/越南/1194/04 HA基因的重组MVA载体(MVA-HA-VN/04)。食蟹猴接受两次免疫,然后用流感病毒A/越南/1194/04(1 clade分支)或A/印度尼西亚/5/05(2.1 clade分支)进行攻毒,以评估保护性免疫水平。

结果

用MVA-HA-VN/04免疫可诱导(交叉反应性)抗体,并防止病毒在上、下呼吸道复制以及严重坏死性支气管间质性肺炎的发生。

结论

因此,MVA-HA-VN/04是一种有前景的候选疫苗,可诱导人类针对高致病性H5N1禽流感病毒产生保护性免疫。

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