Lowen Anice C, Steel John, Mubareka Samira, Carnero Elena, García-Sastre Adolfo, Palese Peter
Department of Microbiology, Mount Sinai School of Medicine, 1 Gustave Levy Pl., New York, NY 10029-6574, USA.
J Virol. 2009 Apr;83(7):2803-18. doi: 10.1128/JVI.02424-08. Epub 2009 Jan 19.
Interventions aimed at preventing viral spread have the potential to effectively control influenza virus in all age groups, thereby reducing the burden of influenza illness. For this reason, we have examined the efficacy of vaccination in blocking the transmission of influenza viruses between guinea pigs. Three modes of immunization were compared: (i) natural infection; (ii) intramuscular administration of whole, inactivated influenza virus in 2 doses; and (iii) intranasal inoculation with live attenuated influenza virus in 2 doses. The ability of each immunization method to block the spread of a homologous (A/Panama/2007/99) H3N2 subtype and a heterologous (A/Wisconsin/67/05) H3N2 subtype influenza virus was tested. We found that previous infection through a natural route provided sterilizing immunity against both homologous and heterologous challenges; thus, no transmission to or from previously infected animals was observed. Vaccination with an inactivated influenza virus vaccine, in contrast, did not prevent guinea pigs from becoming infected upon challenge with either virus. Thus, both intranasal inoculation and exposure to an acutely infected guinea pig led to the infection of vaccinated animals. Vaccination with inactivated virus did, however, reduce viral load upon challenge and decrease the number of secondary transmission events from vaccinated animals to naïve cage mates. Vaccination with a live attenuated virus was found to be more efficacious than vaccination with inactivated virus, resulting in sterilizing immunity against homologous challenge and full protection against the transmission of the homologous and heterologous viruses to naïve contacts. In conclusion, we have shown that the guinea pig model can be used to test influenza virus vaccines and that the efficiency of transmission is a valuable readout when vaccine efficacy is evaluated.
旨在预防病毒传播的干预措施有潜力有效控制所有年龄组的流感病毒，从而减轻流感疾病的负担。因此，我们研究了疫苗接种在阻断豚鼠之间流感病毒传播方面的效果。比较了三种免疫方式：（i）自然感染；（ii）分两剂肌肉注射全灭活流感病毒；（iii）分两剂鼻内接种减毒活流感病毒。测试了每种免疫方法阻断同源（A/巴拿马/2007/99）H3N2亚型和异源（A/威斯康星/67/05）H3N2亚型流感病毒传播的能力。我们发现，先前通过自然途径感染可提供针对同源和异源攻击的无菌免疫；因此，未观察到向先前感染动物的传播或来自先前感染动物的传播。相比之下，用灭活流感病毒疫苗接种并不能防止豚鼠在受到任何一种病毒攻击时被感染。因此，鼻内接种和接触急性感染的豚鼠都会导致接种疫苗的动物被感染。然而，用灭活病毒接种确实降低了攻击后的病毒载量，并减少了从接种疫苗的动物向未接触过病毒的同笼伙伴的二次传播事件数量。发现用减毒活病毒接种比用灭活病毒接种更有效，可产生针对同源攻击的无菌免疫，并全面保护防止同源和异源病毒传播给未接触过病毒的接触者。总之，我们表明豚鼠模型可用于测试流感病毒疫苗，并且在评估疫苗效力时，传播效率是一个有价值的指标。
