See Raymond H, Zakhartchouk Alexander N, Petric Martin, Lawrence David J, Mok Catherine P Y, Hogan Robert J, Rowe Thomas, Zitzow Lois A, Karunakaran Karuna P, Hitt Mary M, Graham Frank L, Prevec Ludvik, Mahony James B, Sharon Chetna, Auperin Thierry C, Rini James M, Tingle Aubrey J, Scheifele David W, Skowronski Danuta M, Patrick David M, Voss Thomas G, Babiuk Lorne A, Gauldie Jack, Roper Rachel L, Brunham Robert C, Finlay B Brett
University of British Columbia Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada.
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
J Gen Virol. 2006 Mar;87(Pt 3):641-650. doi: 10.1099/vir.0.81579-0.
Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.
在小鼠感染模型中，评估了两种不同的严重急性呼吸综合征（SARS）疫苗策略预防活SARS冠状病毒（CoV）攻击的能力。评估了一种全灭活（用β-丙内酯灭活）的SARS-CoV疫苗和两种基于腺病毒的载体的组合，其中一种表达核衣壳（N）蛋白，另一种表达刺突（S）蛋白（统称为Ad S/N），以诱导血清中和抗体和细胞免疫反应，以及它们预防肺部SARS-CoV复制的能力。皮下注射给129S6/SvEv小鼠的全灭活病毒（WKV）疫苗在抑制小鼠呼吸道中SARS-CoV复制方面比鼻内或肌肉注射的Ad S/N疫苗更有效。WKV疫苗的这种保护能力与高血清中和抗体滴度的诱导相关，但与通过小鼠脾细胞分泌γ干扰素测量的细胞免疫反应无关。鼻内或肌肉注射Ad S/N疫苗诱导的血清中和抗体滴度明显低于WKV疫苗诱导的滴度。然而，鼻内注射而非肌肉注射的Ad S/N显著限制了肺部SARS-CoV的复制。在疫苗组中，仅在鼻内接种Ad S/N的小鼠血清中发现了SARS-CoV特异性IgA，这表明粘膜免疫可能在鼻内Ad S/N递送系统的保护中发挥作用。最后，接种疫苗小鼠的血清中含有针对S蛋白的抗体，进一步表明该蛋白在赋予针对SARS-CoV感染的保护性免疫中发挥作用。
