A chimeric haemagglutinin-based influenza split virion vaccine adjuvanted with AS03 induces protective stalk-reactive antibodies in mice.
A chimeric haemagglutinin-based influenza split virion vaccine adjuvanted with AS03 induces protective stalk-reactive antibodies in mice.
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DOI：
10.1038/npjvaccines.2016.15
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发表时间：
2016
期刊：
影响因子：
9.2
通讯作者：
Krammer F
中科院分区：
文献类型：
--
作者：
Nachbagauer R;Kinzler D;Choi A;Hirsh A;Beaulieu E;Lecrenier N;Innis BL;Palese P;Mallett CP;Krammer F
季节性流感病毒疫苗通常在预防疾病方面有效，但需要与流行的病毒株很好地匹配，才能最大限度地受益。流感病毒由于其免疫优势血凝素(HA)头部结构域的高突变率而不断发生抗原性变化，这需要每年重新配制和重新接种疫苗才能持续保护。在大流行性流感病毒暴发的情况下，需要生产并迅速分发新的疫苗。新型流感病毒疫苗将免疫反应重新定向到位于HA茎领域的更保守的表位，可能会消除每年重新配制疫苗的需要，还可以预防人类对免疫幼稚的新出现的大流行毒株。创造这种通用流感病毒疫苗的一种方法是使用表达嵌合HAS的构建体。通过连续免疫表达相同保守的HA茎结构域的疫苗株和宿主幼稚的外来HA头，可以将针对茎的抗体提高到高滴度。在这里，我们测试了一种基于HA的单价嵌合原型通用流感病毒裂解病毒粒子候选疫苗，包括AS03佐剂和不含AS03佐剂的候选疫苗。我们发现，基于HA的嵌合疫苗方案比季节性疫苗诱导出更高的杆状抗体效价。茎抗体反应是持久的，对远亲HAS具有交叉反应，并在体内提供了血清转移攻击模型的保护。这项研究的结果是有希望的，并支持进一步开发建立在嵌合HA技术平台上的通用流感疫苗候选。
Seasonal influenza virus vaccines are generally effective at preventing disease, but need to be well matched to circulating virus strains for maximum benefit. Influenza viruses constantly undergo antigenic changes because of their high mutation rate in the immunodominant haemagglutinin (HA) head domain, which necessitates annual re-formulation and re-vaccination for continuing protection. In case of pandemic influenza virus outbreaks, new vaccines need to be produced and quickly distributed. Novel influenza virus vaccines that redirect the immune response towards more conserved epitopes located in the HA stalk domain may remove the need for annual vaccine re-formulation and could also protect against emergent pandemic strains to which the human population is immunologically naive. One approach to create such universal influenza virus vaccines is the use of constructs expressing chimeric HAs. By sequential immunization with vaccine strains expressing the same conserved HA stalk domain and exotic HA heads to which the host is naive, antibodies against the stalk can be boosted to high titres. Here we tested a monovalent chimeric HA-based prototype universal influenza virus split virion vaccine candidate with and without AS03 adjuvant in primed mice. We found that the chimeric HA-based vaccination regimen induced higher stalk antibody titres than the seasonal vaccine. The stalk antibody responses were long lasting, cross-reactive to distantly related HAs and provided protection in vivo in a serum transfer challenge model. The results of this study are promising and support further development of a universal influenza vaccine candidate built on the chimeric HA technology platform.
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影响因子：
4.4
作者：
Geeraedts F;Bungener L;Pool J;ter Veer W;Wilschut J;Huckriede A
通讯作者：
Huckriede A
影响因子：
3.7
作者：
Krammer F;Margine I;Tan GS;Pica N;Krause JC;Palese P
通讯作者：
Palese P
影响因子：
5.4
作者：
Carter, Donald M.;Darby, Christopher A.;Ross, Ted M.
通讯作者：
Ross, Ted M.
影响因子：
3.1
作者：
BARRY, DW;STATON, E;MAYNER, RE
通讯作者：
MAYNER, RE
DOI：
10.1073/pnas.91.6.2358
发表时间：
1994-03-15
影响因子：
11.1
作者：
JOHANSSON, BE;KILBOURNE, ED
通讯作者：
KILBOURNE, ED