Molecular adjuvant Ag85A enhances protection against influenza A virus in mice following DNA vaccination.

Molecular adjuvant Ag85A enhances protection against influenza A virus in mice following DNA vaccination.
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分子佐剂 Ag85A 在 DNA 疫苗接种后增强小鼠对甲型流感病毒的保护

DOI:
10.3390/v4123606
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发表时间:
2012-12-10
期刊:
Viruses
影响因子:
--
通讯作者:
Li M
Li M
中科院分区:
其他
文献类型:
--
作者:
Dai J;Pei D;Wang B;Kuang Y;Ren L;Cao K;Wang H;Zuo B;Shao J;Li S;Li H;Li M

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设计了一种新型的DNA疫苗载体pEGFP/Ag 85 A-sHA 2(pAg 85 A-sHA 2),该载体编码结核分枝杆菌分泌抗原Ag 85 A与甲型流感病毒(IAV)HA 2蛋白表位的融合蛋白。通过逆转录聚合酶链反应(RT-PCR)和荧光分析确定,由DNA疫苗载体编码的抗原在哺乳动物细胞中有效表达。在用A/波多黎各/8/34病毒(PR 8病毒)攻击之前,通过肌内注射用疫苗载体免疫小鼠。免疫组小鼠血清和脾细胞培养IFN-γ水平均显著高于对照组。新型疫苗组在体外显示出高中和抗体滴度。新型疫苗载体还降低了病毒载量,增加了PR 8病毒攻击后小鼠的存活率,并减少了肺泡炎性细胞数量。在用PR 8病毒攻击后第12天,用新型疫苗载体免疫的小鼠中血清IL-4浓度显著增加。这些结果表明,短的HA 2(sHA 2)蛋白表位可以提供针对PR 8病毒的保护,而Ag 85 A可以增强针对HA 2表位的免疫应答,因此,Ag 85 A可以开发为流感疫苗的新佐剂。
A novel DNA vaccine vector encoding the Mycobacterium tuberculosis secreted antigen Ag85A fused with the influenza A virus (IAV) HA2 protein epitopes, pEGFP/Ag85A-sHA2 (pAg85A-sHA2), was designed to provide protection against influenza. The antigen encoded by the DNA vaccine vector was efficiently expressed in mammalian cells, as determined by reverse transcription polymerase chain reaction (RT-PCR) and fluorescence analyses. Mice were immunized with the vaccine vector by intramuscular injection before challenge with A/Puerto Rico/8/34 virus (PR8 virus). Sera and the splenocyte culture IFN-γ levels were significantly higher in immunized mice compared with the control mice. The novel vaccine group showed a high neutralization antibody titer in vitro. The novel vaccine vector also reduced the viral loads, increased the survival rates in mice after the PR8 virus challenge and reduced the alveolar inflammatory cell numbers. Sera IL-4 concentrations were significantly increased in mice immunized with the novel vaccine vector on Day 12 after challenge with the PR8 virus. These results demonstrated that short HA2 (sHA2) protein epitopes may provide protection against the PR8 virus and that Ag85A could strengthen the immune response to HA2 epitopes, thus, Ag85A may be developed as a new adjuvant for influenza vaccines.
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