Tsunetsugu-Yokota Yasuko, Ato Manabu, Takahashi Yoshimasa, Hashimoto Shu-ichi, Kaji Tomohiro, Kuraoka Masayuki, Yamamoto Ki-ichi, Mitsuki Yu-ya, Yamamoto Takuya, Oshima Masamichi, Ohnishi Kazuo, Takemori Toshitada
Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Jpn J Infect Dis. 2007 May;60(2-3):106-12.
The demand for rapid and simple development of a vaccine against a newly emerging infectious disease is increasing worldwide. We previously revealed that UV-inactivated severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) virions (UV-V) elicited high levels of humoral immunity and a weak Th0 response in mice immunized subcutaneously. To ensure the safety of such a whole inactivated SARS-CoV vaccine, we additionally treated the UV-V vaccine with formalin, resulting in the UV-F-V vaccine. Analysis of the immunogenicity of the UV-F-V+alum vaccine in mice revealed that it generated comparable neutralizing serum anti-SARS-CoV IgG antibody levels as the UV-V+alum vaccine. Moreover, both vaccines induced similar frequencies of anti-SARS-CoV IgG antibody-producing cells in bone marrow. Interestingly, the UV-F-V vaccine induced fewer IgG(2a) subtype antibodies and higher interleukin-4 production in vaccinated mice than did UV-V. Thus, UV-F-V imposes a Th2-type bias on the immune response, unlike UV-V. We propose here that doubly-inactivated SARS-CoV virions by UV and formalin constitute a safe vaccine that may effectively induce neutralizing antibodies in humans.
全球范围内，针对新出现的传染病快速、简便地研发疫苗的需求日益增加。我们之前发现，紫外线灭活的严重急性呼吸综合征（SARS）相关冠状病毒（SARS-CoV）病毒粒子（UV-V）在皮下免疫的小鼠中可引发高水平的体液免疫和较弱的Th0反应。为确保这种全灭活SARS-CoV疫苗的安全性，我们用福尔马林对UV-V疫苗进行了额外处理，得到了UV-F-V疫苗。对UV-F-V+明矾疫苗在小鼠中的免疫原性分析表明，它产生的中和血清抗SARS-CoV IgG抗体水平与UV-V+明矾疫苗相当。此外，两种疫苗在骨髓中诱导产生抗SARS-CoV IgG抗体的细胞频率相似。有趣的是，与UV-V相比，UV-F-V疫苗在接种小鼠中诱导产生的IgG(2a)亚型抗体较少，白细胞介素-4产量较高。因此，与UV-V不同，UV-F-V在免疫反应上呈现Th2型偏向。我们在此提出，经紫外线和福尔马林双重灭活的SARS-CoV病毒粒子构成一种安全的疫苗，可能有效地在人体中诱导产生中和抗体。
