Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate

Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate
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DOI:
10.1089/vim.2017.0022
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发表时间:
2017-07-01
期刊:
影响因子:
2.2
通讯作者:
Hasegawa, Hideki
Hasegawa, Hideki
中科院分区:
医学4区
文献类型:
--
作者:
Ainai, Akira;Suzuki, Tadaki;Hasegawa, Hideki

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目前的流感疫苗是一种通过皮下/肌肉注射施用的灭活病毒疫苗,其效果仅限于降低与季节性流感爆发相关的发病率和死亡率。相比之下,鼻内疫苗接种模仿自然感染,不仅诱导全身 IgG 抗体,还诱导上呼吸道粘膜上皮表面的局部分泌型 IgA (S-IgA) 抗体。 S-IgA 抗体对于预防病毒感染非常有效。尽管鼻内注射的减毒活流感疫苗 (LAIV) 可以诱导局部抗体,但由于在疫苗中使用活病毒的安全性问题,该疫苗仅限于 2-49 岁的健康人群。用灭活病毒制成的鼻内疫苗可以代替 LAIV,适用于高危人群,包括婴儿和老年人。通常,需要粘膜佐剂来增强灭活流感疫苗鼻内疫苗接种的效果。然而,我们发现,在没有任何粘膜佐剂的情况下,鼻内施用浓缩的全灭活流感病毒疫苗足以在对季节性流感病毒具有一定免疫记忆的健康个体的鼻上皮中诱导局部中和S-IgA抗体。这种鼻内疫苗是一种新型候选疫苗,可以改进目前的注射疫苗或 LAIV,用于预防季节性流感流行。
The effect of the current influenza vaccine, an inactivated virus vaccine administered by subcutaneous/intramuscular injection, is limited to reducing the morbidity and mortality associated with seasonal influenza outbreaks. Intranasal vaccination, by contrast, mimics natural infection and induces not only systemic IgG antibodies but also local secretory IgA (S-IgA) antibodies found on the surface of the mucosal epithelium in the upper respiratory tract. S-IgA antibodies are highly effective at preventing virus infection. Although the live attenuated influenza vaccine (LAIV) administered intranasally can induce local antibodies, this vaccine is restricted to healthy populations aged 2-49 years because of safety concerns associated with using live viruses in a vaccine. Instead of LAIV, an intranasal vaccine made with inactivated virus could be applied to high-risk populations, including infants and elderly adults. Normally, a mucosal adjuvant would be required to enhance the effect of intranasal vaccination with an inactivated influenza vaccine. However, we found that intranasal administration of a concentrated, whole inactivated influenza virus vaccine without any mucosal adjuvant was enough to induce local neutralizing S-IgA antibodies in the nasal epithelium of healthy individuals with some immunological memory for seasonal influenza viruses. This intranasal vaccine is a novel candidate that could improve on the current injectable vaccine or the LAIV for the prevention of seasonal influenza epidemics.