Blocking Interhost Transmission of Influenza Virus by Vaccination in the Guinea Pig Model
Blocking Interhost Transmission of Influenza Virus by Vaccination in the Guinea Pig Model
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DOI：
10.1128/jvi.02424-08
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发表时间：
2009-04-01
影响因子：
5.4
通讯作者：
Palese, Peter
中科院分区：
文献类型：
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作者：
Lowen, Anice C.;Steel, John;Palese, Peter
旨在预防病毒传播的干预措施有可能在所有年龄组中有效控制流感病毒，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有效性。比较了三种免疫接种模式：（i）自然感染;（ii）肌内接种2剂完整的灭活流感病毒;和（iii）鼻内接种2剂减毒活流感病毒。测试了每种免疫方法阻断同源（A/Panama/2007/99）H3 N2亚型和异源（A/威斯康星州/67/05）H3 N2亚型流感病毒传播的能力。我们发现，以前通过自然途径感染提供了对同源和异源挑战的灭菌免疫力;因此，没有观察到以前感染动物的传播。相比之下，接种灭活流感病毒疫苗并不能防止豚鼠在受到任何一种病毒的攻击后受到感染。因此，鼻内接种和暴露于急性感染豚鼠均导致接种动物感染。然而，接种灭活病毒确实降低了攻毒后的病毒载量，并减少了从接种疫苗的动物到未接种疫苗的笼友的二次传播事件的数量。发现用活的减毒病毒接种比用灭活病毒接种更有效，导致针对同源攻击的灭菌免疫和针对同源和异源病毒向未感染接触者的传播的完全保护。总之，我们已经表明，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读数。
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 naive 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 naive 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.