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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mucosal and systemic adjuvant activity of alphavirus replicon particles
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Mucosal and systemic adjuvant activity of alphavirus replicon particles

机译：α病毒复制子颗粒的粘膜和全身佐剂活性

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Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines.
机译：疫苗接种是对抗传染病最有效的控制措施。局部粘膜免疫反应对于保护和解决多种粘膜病原体感染至关重要。跨粘膜表面的抗原加工是产生粘膜免疫力的自然途径，因为外周抗原递送通常不能诱导粘膜免疫反应。但是，我们在本文中证明委内瑞拉马脑炎病毒复制子颗粒（VRP）的肠胃外给药后，在多个粘膜表面可见粘膜免疫反应。此外，与单独的抗原相比，无效的VRP（不表达任何转基因）与灭活的流感病毒粒子或卵清蛋白的共接种会导致抗原特异性全身性IgG和粪便IgA抗体显着增加。用紫外线对VRP进行预处理可以大大消除这种辅助作用。这些结果表明，甲病毒复制子颗粒具有固有的全身性和粘膜佐剂活性，并表明VRP RNA复制是该活性的触发因素。我们认为，这些观察结果和它们刺激的持续实验将最终确定诱导粘膜免疫的另一种途径的特定组成部分，并且如果该活性在人类中很明显，将为安全和廉价的亚单位和灭活疫苗提供新的可能性。

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