Lokugamage Kumari G, Yoshikawa-Iwata Naoko, Ito Naoto, Watts Douglas M, Wyde Philip R, Wang Nan, Newman Patrick, Kent Tseng Chien-Te, Peters C J, Makino Shinji
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, United States.
Vaccine. 2008 Feb 6;26(6):797-808. doi: 10.1016/j.vaccine.2007.11.092. Epub 2007 Dec 26.
We tested the efficacy of coronavirus-like particles (VLPs) for protecting mice against severe acute respiratory syndrome coronavirus (SCoV) infection. Coexpression of SCoV S protein and E, M and N proteins of mouse hepatitis virus in 293T or CHO cells resulted in the efficient production of chimeric VLPs carrying SCoV S protein. Balb/c mice inoculated with a mixture of chimeric VLPs and alum twice at an interval of four weeks were protected from SCoV challenge, as indicated by the absence of infectious virus in the lungs. The same groups of mice had high levels of SCoV-specific neutralizing antibodies, while mice in the negative control groups, which were not immunized with chimeric VLPs, failed to manifest neutralizing antibodies, suggesting that SCoV-specific neutralizing antibodies are important for the suppression of viral replication within the lungs. Despite some differences in the cellular composition of inflammatory infiltrates, we did not observe any overt lung pathology in the chimeric-VLP-treated mice, when compared to the negative control mice. Our results show that chimeric VLP can be an effective vaccine strategy against SCoV infection.
我们测试了冠状病毒样颗粒(VLPs)保护小鼠免受严重急性呼吸综合征冠状病毒(SCoV)感染的功效。在293T或CHO细胞中共表达SCoV S蛋白以及小鼠肝炎病毒的E、M和N蛋白,可有效产生携带SCoV S蛋白的嵌合VLPs。间隔四周给Balb/c小鼠两次接种嵌合VLPs与明矾的混合物后,小鼠受到了保护,免受SCoV攻击,肺部未检测到传染性病毒即为证明。相同组别的小鼠具有高水平的SCoV特异性中和抗体,而未用嵌合VLPs免疫的阴性对照组小鼠则未表现出中和抗体,这表明SCoV特异性中和抗体对于抑制肺部病毒复制很重要。尽管炎性浸润的细胞组成存在一些差异,但与阴性对照小鼠相比,我们在接受嵌合VLP治疗的小鼠中未观察到任何明显的肺部病变。我们的结果表明,嵌合VLP可能是一种有效的抗SCoV感染疫苗策略。