Inactivated whole influenza virus particle vaccines induce neutralizing antibodies with an increase in immunoglobulin gene subclones of B-lymphocytes in cynomolgus macaques
Inactivated whole influenza virus particle vaccines induce neutralizing antibodies with an increase in immunoglobulin gene subclones of B-lymphocytes in cynomolgus macaques
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DOI：
10.1016/j.vaccine.2022.05.045
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发表时间：
2022-06-26
期刊：
影响因子：
5.5
通讯作者：
Itoh，Yasushi
中科院分区：
文献类型：
--
作者：
Shiohara，Masanori;Suzuki，Saori;Itoh，Yasushi
全日本流感疫苗研究小组一直在开发一种比目前针对季节性流感病毒感染的裂解疫苗更有效的疫苗。在本研究中，在非人灵长类动物模型中比较了福尔马林和/或β-丙内酯灭活的全病毒颗粒疫苗与当前乙醚处理的裂解疫苗对季节性流感的有效性。将甲型H1N1流感病毒和B流感病毒（维多利亚谱系）的单价全病毒颗粒疫苗或裂解疫苗皮下注射至未感染的食蟹猴中两次。与裂解疫苗相比，全病毒颗粒疫苗在猕猴血浆中诱导了更高滴度的针对H1N1甲型流感病毒和B型流感病毒的中和抗体。在用甲型H1N1流感病毒或乙型流感B病毒攻击时，用全病毒颗粒疫苗免疫的猕猴的鼻拭子中的病毒滴度和体温升高低于用裂解疫苗免疫的猕猴。免疫球蛋白重链基因的库分析表明，在第一次接种全病毒颗粒疫苗后，猕猴中B淋巴细胞亚克隆的数量增加，但裂解疫苗没有增加，表明全病毒颗粒疫苗诱导疫苗抗原特异性B淋巴细胞的活化比裂解疫苗在引发时更强烈。因此，本研究结果表明，与裂解疫苗相比，全病毒颗粒疫苗的上级抗体诱导能力归因于其对抗原特异性B淋巴细胞亚克隆分化的刺激特性。
The All-Japan Influenza Vaccine Study Group has been developing a more effective vaccine than the current split vaccines for seasonal influenza virus infection. In the present study, the efficacy of formalin- and/or β-propiolactone-inactivated whole virus particle vaccines for seasonal influenza was compared to that of the current ether-treated split vaccines in a nonhuman primate model. The monovalent whole virus particle vaccines or split vaccines of influenza A virus (H1N1) and influenza B virus (Victoria lineage) were injected subcutaneously into naïve cynomolgus macaques twice. The whole virus particle vaccines induced higher titers of neutralizing antibodies against H1N1 influenza A virus and influenza B virus in the plasma of macaques than did the split vaccines. At challenge with H1N1 influenza A virus or influenza B virus, the virus titers in nasal swabs and the increases in body temperatures were lower in the macaques immunized with the whole virus particle vaccine than in those immunized with the split vaccine. Repertoire analyses of immunoglobulin heavy chain genes demonstrated that the number of B-lymphocyte subclones was increased in macaques after the 1st vaccination with the whole virus particle vaccine, but not with the split vaccine, indicating that the whole virus particle vaccine induced the activation of vaccine antigen-specific B-lymphocytes more vigorously than did the split vaccine at priming. Thus, the present findings suggest that the superior antibody induction ability of the whole virus particle vaccine as compared to the split vaccine is attributable to its stimulatory properties on the subclonal differentiation of antigen-specific B-lymphocytes.