A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice
A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice
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DOI：
10.1093/intimm/dxh143
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发表时间：
2004-10-01
影响因子：
4.4
通讯作者：
Tsunetsugu-Yokota, Y
中科院分区：
文献类型：
--
作者：
Takasuka, N;Fujii, H;Tsunetsugu-Yokota, Y
最近出现的严重急性呼吸综合征（SARS）是由一种新型冠状病毒SARS-CoV引起的。它迅速蔓延到许多国家，现在迫切需要开发SARS疫苗。为了研究紫外线灭活的纯化SARS冠状病毒粒子作为疫苗候选物的免疫原性，我们用紫外线灭活的SARS冠状病毒在有或没有佐剂的情况下皮下免疫小鼠。我们选择氢氧化铝凝胶（明矾）作为佐剂，因为它对人类使用的安全历史很长。我们观察到，紫外线灭活的SARS-CoV病毒粒子引发了高水平的体液免疫，导致产生长期抗体分泌和记忆B细胞。在疫苗配方中加入明矾后，血清IgG产生增加，并达到与超免疫小鼠相似的水平，但仍不足以引发血清IgA抗体。值得注意的是，SARS-CoV病毒粒子本身即使没有佐剂也能够诱导长期抗体产生。在小鼠中引发的抗SARS-CoV抗体识别病毒的刺突蛋白和核衣壳蛋白，并且能够中和病毒。此外，在体外用灭活的SARS-CoV病毒粒子重新刺激后，紫外线灭活的病毒粒子诱导局部淋巴结T细胞增殖和显着水平的细胞因子（IL-2、IL-4、IL-5、IFN-γ和TNF-α）产生。因此，完整的灭活病毒粒子可以作为SARS疫苗的候选抗原，以引起体液和细胞免疫。
The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.