Lu X, Tumpey T M, Morken T, Zaki S R, Cox N J, Katz J M
Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
J Virol. 1999 Jul;73(7):5903-11. doi: 10.1128/JVI.73.7.5903-5911.1999.
During 1997 in Hong Kong, 18 human cases of respiratory illness, including 6 fatalities, were caused by highly pathogenic avian influenza A (H5N1) viruses. Since H5 viruses had previously been isolated only from avian species, the outbreak raised questions about the ability of these viruses to cause severe disease and death in humans. To better understand the pathogenesis and immunity to these viruses, we have used the BALB/c mouse model. Four H5N1 viruses replicated equally well in the lungs of mice without prior adaptation but differed in lethality for mice. H5N1 viruses that were highly lethal for mice were detected in multiple organs, including the brain. This is the first demonstration of an influenza A virus that replicates systemically in a mammalian species and is neurotropic without prior adaptation. The mouse model was also used to evaluate a strategy of vaccination against the highly pathogenic avian H5N1 viruses, using an inactivated vaccine prepared from nonpathogenic A/Duck/Singapore-Q/F119-3/97 (H5N3) virus that was antigenically related to the human H5N1 viruses. Mice administered vaccine intramuscularly, with or without alum, were completely protected from lethal challenge with H5N1 virus. Protection from infection was also observed in 70% of animals administered vaccine alone and 100% of mice administered vaccine with alum. The protective effect of vaccination correlated with the level of virus-specific serum antibody. These results suggests a strategy of vaccine preparedness for rapid intervention in future influenza pandemics that uses antigenically related nonpathogenic viruses as vaccine candidates.
1997年在香港，18例人类呼吸道疾病病例，其中6例死亡，是由高致病性甲型禽流感（H5N1）病毒引起的。由于此前仅从禽类中分离出H5病毒，此次疫情引发了关于这些病毒导致人类严重疾病和死亡能力的疑问。为了更好地了解这些病毒的发病机制和免疫情况，我们使用了BALB/c小鼠模型。四种H5N1病毒在未经预先适应的情况下在小鼠肺部的复制情况相同，但对小鼠的致死性不同。对小鼠具有高致死性的H5N1病毒在包括大脑在内的多个器官中被检测到。这是首次证明甲型流感病毒在哺乳动物物种中全身复制且具有嗜神经性，无需预先适应。该小鼠模型还用于评估针对高致病性禽H5N1病毒的疫苗接种策略，使用由与人类H5N1病毒抗原相关的非致病性A/鸭/新加坡-Q/F119-3/97（H5N3）病毒制备的灭活疫苗。肌肉注射疫苗（有无明矾佐剂）的小鼠完全受到保护，免受H5N1病毒的致死性攻击。仅接种疫苗的动物中有70%以及接种疫苗并使用明矾佐剂的小鼠中有100%观察到对感染的保护作用。疫苗接种的保护效果与病毒特异性血清抗体水平相关。这些结果提示了一种疫苗储备策略，用于在未来流感大流行时进行快速干预，即使用抗原相关的非致病性病毒作为候选疫苗。
