Lee So-Young, Kang Jung-Ok, Chang Jun
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Clin Exp Vaccine Res. 2019 Jan;8(1):54-63. doi: 10.7774/cevr.2019.8.1.54. Epub 2019 Jan 31.
The influenza B virus diverges into two antigenically distinct lineages: B/Yamagata and B/Victoria. Influenza B is the dominant circulating virus during some influenza seasons, and recent data demonstrated that influenza A and B infection similarly cause severe clinical symptoms in hospitalized patients. Nucleoprotein (NP) is a good target for a universal influenza vaccine. This study investigated whether NP epitope variation within two lineages affects the dominant cytotoxic T lymphocyte (CTL) responses induced by vaccination and the resultant protective immunity.
The NP of B/Yamagata/16/1988, the representative strain of the Yamagata lineage, includes a dominant CTL epitope, FSPIRITFL, while B/Shangdong/7/1997 from the Victoria lineage has one amino acid difference in this sequence, FSPIRVTFL. Two recombinant replication-deficient adenovirus (rAd)-vectored vaccines expressing either NP were prepared (rAd/B-NP(I) and rAd/B-NP(V), respectively) and administered to BALB/c mice intranasally. To examine the efficacy of vaccination, antibody responses, CTL responses, and morbidity/mortality after challenge were measured.
Both vaccines induce similar antibody and CD8 T-cell responses cross-reacting to both epitopes, and also confer cross-protection against both lineages regardless of amino acid difference.
The rAd-vectored vaccine expressing the NP could be developed as universal influenza B vaccine which provides broader protection.
乙型流感病毒分为两个抗原性不同的谱系:B/山形系和B/维多利亚系。在某些流感季节,乙型流感是主要的流行病毒,最近的数据表明,甲型和乙型流感感染在住院患者中同样会引起严重的临床症状。核蛋白(NP)是通用流感疫苗的一个良好靶点。本研究调查了两个谱系内NP表位变异是否会影响疫苗接种诱导的主要细胞毒性T淋巴细胞(CTL)反应以及由此产生的保护性免疫。
山形谱系的代表性毒株B/山形/16/1988的NP包含一个主要的CTL表位FSPIRITFL,而来自维多利亚谱系的B/山东/7/1997在该序列中有一个氨基酸差异,即FSPIRVTFL。制备了两种分别表达NP的重组复制缺陷腺病毒(rAd)载体疫苗(分别为rAd/B-NP(I)和rAd/B-NP(V)),并通过鼻内给药的方式给予BALB/c小鼠。为了检测疫苗接种的效果,测量了抗体反应、CTL反应以及攻毒后的发病率/死亡率。
两种疫苗均诱导出对两个表位产生交叉反应的相似抗体和CD8 T细胞反应,并且无论氨基酸差异如何,均对两个谱系提供交叉保护。
表达NP的rAd载体疫苗可开发为提供更广泛保护的通用乙型流感疫苗。