Zhang Chuan-Hai, Guo Zhong-Min, Zheng Huan-Ying, Lu Jia-Hai, Wang Yi-Fei, Yan Xin-Ge, Zhao Yong, DU Xiong-Wei, Zhang Xin, Fang Ling, Ling Wen-Hua, Qi Shu-Yuan, Yu Xin-Bing, Zhong Nan-Shan
South China Institute of Botany, Graduate School of Chinese Academy of Sciences, Guangzhou 510650, China.
Chin Med J (Engl). 2004 Nov;117(11):1625-9.
The etiologic agent of severe acute respiratory syndrome (SARS) has been confirmed to be a novel coronavirus (CoV), namely SARS-CoV. Developing safe and effective SARS-CoV vaccines is essential for us to prevent the possible reemergence of its epidemic. Previous experiences indicate that inactivated vaccine is conventional and more hopeful to be successfully developed. Immunogenicity evaluation of an experimental inactivated SARS-CoV vaccine in rabbits was conducted and reported in this paper.
The large-scale cultured SARS-CoV F69 strain was inactivated with 0.4% formaldehyde and purified, then used as the immunogen combined with Freund's adjuvant. Eight adult New Zealand rabbits were immunized four times with this experimental inactivated vaccine. Twelve sets of rabbit serum were sampled from the third day to the seventy-fourth day after the first vaccination. The titers of specific anti-SARS-CoV IgG antibody were determined by indirect enzyme-linked immunosorbent assay, and the neutralizing antibody titers were detected with micro-cytopathic effect neutralization test.
Rapid and potent humoral immune responses were induced by the inactivated SARS-CoV vaccine in all the eight test rabbits. Titers of both specific IgG antibody and neutralizing antibody peaked at about six weeks after first vaccination, with the maximum value of 1:81 920 and 1:20 480, respectively. After that, serum antibody levels remained at a plateau or had a slight decrease, though two boosters were given in the succedent 4 to 5 weeks. Cross neutralization response existed between SARS-CoV F69 strain and Z2-Y3 strain.
The inactivated SARS-CoV vaccine made from F69 strain owns strong immunogenicity, and the cross neutralization response between the two different SARS-CoV strains gives a hint of the similar neutralizing epitopes, which provide stable bases for the development of inactivated SARS-CoV vaccines.
严重急性呼吸综合征（SARS）的病原体已被确认为一种新型冠状病毒（CoV），即SARS-CoV。研发安全有效的SARS-CoV疫苗对于预防其疫情可能的再次出现至关重要。以往经验表明，灭活疫苗是传统的且更有希望成功研发。本文报道了一种实验性SARS-CoV灭活疫苗在兔体内的免疫原性评价。
用0.4%甲醛对大规模培养的SARS-CoV F69株进行灭活并纯化，然后与弗氏佐剂结合用作免疫原。8只成年新西兰兔用这种实验性灭活疫苗免疫4次。在首次接种疫苗后的第3天至第74天采集12组兔血清。通过间接酶联免疫吸附测定法测定特异性抗SARS-CoV IgG抗体的滴度，并用微量细胞病变效应中和试验检测中和抗体滴度。
灭活的SARS-CoV疫苗在所有8只受试兔中诱导了快速而有效的体液免疫反应。特异性IgG抗体和中和抗体的滴度在首次接种疫苗后约6周达到峰值，最大值分别为1:81 920和1:20 480。此后，尽管在随后的4至5周内进行了两次加强免疫，但血清抗体水平保持在平台期或略有下降。SARS-CoV F69株和Z2-Y3株之间存在交叉中和反应。
由F69株制成的灭活SARS-CoV疫苗具有很强的免疫原性，两种不同SARS-CoV株之间的交叉中和反应提示了相似的中和表位，这为灭活SARS-CoV疫苗的研发提供了稳定的基础。
