Experimental Groups for Evaluation of SARS Coronavirus Vaccines.

1Design = All experiments in Balb/c mice except as noted in Exp 3. Each group contained 12–13 mice; all were given 100 µl of vaccine IM at dosages with or without alum as indicated on days 0 and 28 except as noted. Five mice in each group were sacrificed on day 56 for serum antibody; remaining mice were given 106 TCID50 of SARS-CoV intranasal on day 56 and sacrificed on day 58 for virus and lung histology.2DIV/dosage = Vaccine DIV = Zonal centrifuge purified doubly inactivated (formalin and UV) whole virus SV/dosage = Vaccine SV = Recombinant baculovirus expressed S glycoprotein of SARS-CoV VLP/dosage = Vaccine VLP = Virus-like particles containing SARS-CoV S glycoprotein and E, M, and N proteins from mouse hepatitis coronavirus BPV/dosage = Vaccine BPV = Purified beta propiolactone inactivated whole virus plus alum.3Experiment 3 = Groups 1 to 7 were Balb/c mice; groups 8 to 14 were C57BL/6 mice. Flu vaccine was licensed trivalent 2009-10 formulation of high dosage vaccine (60 µg of HA of each strain). Groups 1 and 8 were given PBS (placebo) and challenged with PBS; all others were challenged with live SARS-CoV.

1. 实验设计：除实验3外，所有实验均使用巴尔贝/c（Balb/c）小鼠。每组包含12~13只小鼠，除特殊说明外，各组均于第0天和第28天行肌内（intramuscular, IM）注射100 μL不同剂量的疫苗，佐剂含或不含明矾（alum）。每组于第56天处死5只小鼠以采集血清检测抗体；剩余小鼠于同日经鼻内接种10^6 半数组织培养感染剂量（50% Tissue Culture Infectious Dose, TCID₅₀）的严重急性呼吸综合征冠状病毒（SARS-CoV），并于第58天处死以开展病毒检测及肺组织病理学分析。
2. 疫苗类型与剂量：
DIV组疫苗（Vaccine DIV）：经区带离心机（zonal centrifuge）纯化的双重灭活（甲醛与紫外线）全病毒疫苗；
SV组疫苗（Vaccine SV）：由重组杆状病毒（recombinant baculovirus）表达的严重急性呼吸综合征冠状病毒S糖蛋白疫苗；
VLP组疫苗（Vaccine VLP）：包含严重急性呼吸综合征冠状病毒S糖蛋白，以及鼠肝炎冠状病毒E、M、N蛋白的病毒样颗粒（Virus-like particles, VLP）；
BPV组疫苗（Vaccine BPV）：经纯化的β-丙内酯（beta propiolactone）灭活全病毒疫苗，辅以明矾佐剂。
3. 实验3：第1~7组为巴尔贝/c（Balb/c）小鼠，第8~14组为C57BL/6小鼠。所用流感疫苗为获批的2009-2010年度三价高剂量配方疫苗，每株毒株的血凝素（Hemagglutinin, HA）含量为60 μg。第1组和第8组经注射磷酸盐缓冲液（Phosphate Buffered Saline, PBS，安慰剂）并以PBS攻毒；其余所有组别均以活严重急性呼吸综合征冠状病毒攻毒。