Comparison of vaccination efficacy using live or ultraviolet-inactivated influenza viruses introduced by different routes in a mouse model.

Comparison of vaccination efficacy using live or ultraviolet-inactivated influenza viruses introduced by different routes in a mouse model.
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DOI:
10.1371/journal.pone.0275722
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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流感是高度传染性呼吸道疾病的一个主要原因,导致世界范围内的高死亡率和发病率。每年接种疫苗是预防流感病毒株不断变异引起的感染和并发症的有效方法。疫苗接种利用预先接种活病毒、活减毒病毒、灭活病毒或病毒片段以获得最佳免疫激活。接种途径也会影响疫苗的效力。在这里,我们评估了接种紫外线(UV)灭活或活甲型流感病毒株的影响,并比较了它们的有效性和交叉保护时,腹腔内和肌肉注射给药途径在小鼠中使用。用UV灭活的流感A/WSN/1933进行肌内或腹膜内接种提供了对用致死剂量的活流感A/WSN/1933进行鼻内攻击的一些保护,但仅当在接种中使用高剂量的病毒时。相比之下,通过任一途径接种低剂量活病毒可提供针对相同鼻内攻击的完全保护。用活的或UV灭活的Influenza A/Philippines/2/1982腹膜内接种和用UV灭活的Influenza A/Philippines/2/1982肌内接种未能产生针对Influenza A/WSN/1933的交叉反应性抗体。用活的流感A/Philippines/2/1982肌内接种诱导少量交叉反应性抗体,但不能抑制用流感A/WSN/1993鼻内激发后产生的细胞因子风暴。检测的接种条件均未提供针对不同流感病毒株鼻内攻毒的可观察到的交叉保护。总之,疫苗接种效力受疫苗病毒状态和剂量以及给药途径的影响。这些结果为研制有效的流感病毒疫苗提供了实用数据。
Influenza is a major cause of highly contagious respiratory illness resulting in high mortality and morbidity worldwide. Annual vaccination is an effective way to prevent infection and complication from constantly mutating influenza strains. Vaccination utilizes preemptive inoculation with live virus, live attenuated virus, inactivated virus, or virus segments for optimal immune activation. The route of administration also affects the efficacy of the vaccination. Here, we evaluated the effects of inoculation with ultraviolet (UV)-inactivated or live influenza A virus strains and compared their effectiveness and cross protection when intraperitoneal and intramuscular routes of administration were used in mice. Intramuscular or intraperitoneal inoculation with UV-inactivated Influenza A/WSN/1933 provided some protection against intranasal challenge with a lethal dose of live Influenza A/WSN/1933 but only when a high dose of the virus was used in the inoculation. By contrast, inoculation with a low dose of live virus via either route provided complete protection against the same intranasal challenge. Intraperitoneal inoculation with live or UV-inactivated Influenza A/Philippines/2/1982 and intramuscular inoculation with UV-inactivated Influenza A/Philippines/2/1982 failed to produce cross-reactive antibodies against Influenza A/WSN/1933. Intramuscular inoculation with live Influenza A/Philippines/2/1982 induced small amounts of cross-reactive antibodies but could not suppress the cytokine storm produced upon intranasal challenge with Influenza A/WSN/1993. None of the tested inoculation conditions provided observable cross protection against intranasal challenge with a different influenza strain. Taken together, vaccination efficacy was affected by the state and dose of the vaccine virus and the route of administration. These results provide practical data for the development of effective vaccines against influenza virus.
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