Enhanced humoral response to influenza vaccine in aged mice with a novel adjuvant, rOv-ASP-1.
Enhanced humoral response to influenza vaccine in aged mice with a novel adjuvant, rOv-ASP-1.
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DOI：
10.1016/j.vaccine.2016.01.003
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发表时间：
2016-02-10
期刊：
影响因子：
5.5
通讯作者：
Murasko DM
中科院分区：
文献类型：
--
作者：
Jiang J;Fisher EM;Concannon M;Lustigman S;Shen H;Murasko DM
TIV + rOv-ASP-1免疫老年小鼠后流感特异性抗体水平显著升高。rOv-ASP-1在诱导老年小鼠TIV免疫后特异性IgG方面优于常规佐剂明矾（上级）。rOv-ASP-1的共同给药诱导交叉反应性抗体并增强交叉保护。免疫接种是预防季节性流行病和流感大流行的最佳方法。在美国有两种流感疫苗：灭活疫苗（TIV）和减毒疫苗;然而，只有TIV被批准用于老年人群的免疫接种。虽然老年人口的流感疫苗接种率最高，但保护效力较低，老年人与流感相关的死亡率最高。最近，我们报道了一种从寄生蠕虫盘尾丝虫（Onchocerca volvulus）中提取的佐剂，命名为O。肠扭转激活相关分泌蛋白-1（Ov-ASP-1）可显著增强灭活疫苗（TIV）在年轻成年小鼠中的保护效力。在目前的研究中，我们检查了这种重组Ov-ASP-1（rOv-ASP-1）是否也可以增强老年小鼠中TIV的疗效。虽然用TIV单独初次免疫在老年小鼠中仅产生低水平的流感特异性抗体（总IgG、IgG 1和IgG 2c），但用TIV + rOv-ASP-1免疫后抗体水平显著增加。更重要的是，施用TIV + rOv-ASP-1的老年小鼠中的总IgG水平与仅用TIV免疫的年轻成年小鼠的总IgG水平相当。rOv-ASP-1的共同给药诱导了低水平的交叉反应性抗体，并增强了TIV在老年小鼠中的保护功效，这反映在用异源流感病毒攻击后存活率显著增加。rOv-ASP-1在老年小鼠中TIV免疫后诱导特异性IgG以及在攻击后赋予保护方面也上级常规佐剂明矾。这些结果表明，rOv-ASP-1可以作为流感疫苗的潜在佐剂，以提高老年人的保护效果。
Influenza-specific antibody levels were significantly increased after immunization with TIV + rOv-ASP-1 in aged mice. rOv-ASP-1 was superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice. Co-administration of rOv-ASP-1 induced cross-reactive antibody and enhanced cross-protection. Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV + rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV + rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly.