Ainai Akira, Suzuki Tadaki, Tamura Shin-Ichi, Hasegawa Hideki
Department of Pathology, National Institute of Infectious Diseases , Tokyo, Japan .
Viral Immunol. 2017 Jul/Aug;30(6):451-462. doi: 10.1089/vim.2017.0022. Epub 2017 Jun 26.
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.
目前的流感疫苗是一种通过皮下/肌肉注射给药的灭活病毒疫苗,其作用仅限于降低与季节性流感暴发相关的发病率和死亡率。相比之下,鼻内接种疫苗模拟自然感染,不仅能诱导全身性IgG抗体,还能诱导在上呼吸道黏膜上皮表面发现的局部分泌型IgA(S-IgA)抗体。S-IgA抗体在预防病毒感染方面非常有效。虽然鼻内接种的减毒活流感疫苗(LAIV)可诱导局部抗体,但由于疫苗中使用活病毒存在安全问题,这种疫苗仅限于2至49岁的健康人群使用。用灭活病毒制成的鼻内疫苗可用于包括婴儿和老年人在内的高危人群,以替代LAIV。通常,需要一种黏膜佐剂来增强灭活流感疫苗鼻内接种的效果。然而,我们发现,鼻内接种浓缩的全灭活流感病毒疫苗,无需任何黏膜佐剂,就足以在对季节性流感病毒有一定免疫记忆的健康个体的鼻上皮中诱导产生局部中和性S-IgA抗体。这种鼻内疫苗是一种新型候选疫苗,有望在预防季节性流感流行方面优于目前的注射用疫苗或LAIV。