Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus

Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus
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DOI:
10.1016/j.vaccine.2017.01.008
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发表时间:
2017-02-15
期刊:
影响因子:
5.5
通讯作者:
Ogasawara, Kazumasa
Ogasawara, Kazumasa
中科院分区:
医学3区
文献类型:
--
作者:
Nakayama, Misako;Itoh, Yasushi;Ogasawara, Kazumasa

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在猕猴模型中,通过鼻内注射少量灭活的全病毒颗粒和人源性H5N1高致病性禽流感病毒感染,研究了粘膜接种灭活流感疫苗的疗效和有害影响。反复鼻腔接种灭活病毒A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3)全颗粒疫苗,可诱导鼻拭子和血浆中产生抗原特异性IgA和IgG抗体。在鼻拭子中也发现了vac3特异性IgE的产生。与皮下接种相比,鼻腔接种vac3可诱导更广泛的跨枝中和活性。在攻毒感染后,反复鼻腔接种疫苗几乎完全阻止了病毒在上、下呼吸道的传播,并通过诱导肺中产生iga的B细胞保护食蟹猴免受病毒性肺炎。另一方面,在接种疫苗的猕猴肺中观察到嗜酸性粒细胞聚集。尽管与感染前相比,感染后vac3特异性IgE抗体和IL-13水平下降,并且接种疫苗的猕猴在攻击感染后未检测到过敏反应,但我们的研究结果表明,我们必须注意重复鼻腔接种疫苗的潜在过敏反应,特别是对气道过敏的人。(C) 2017 Elsevier Ltd.版权所有。
The efficacy and detrimental effect of mucosal vaccination with an inactivated influenza vaccine were examined in a macaque model by intranasal administration with small amounts of inactivated whole virus particles and challenge by a human-derived H5N1 highly pathogenic avian influenza virus infection. Repeated nasal inoculation with the whole particle vaccine of an inactivated virus, A/duck/Hokkaido/Vac-3/2007 (H5N1) (Vac-3), induced antigen-specific IgA and IgG antibody production in nasal swabs and plasma. Vac-3-specific IgE production was also found in the nasal swabs. Nasal vaccination with Vac-3 induced broader cross-clade neutralization activity than did subcutaneous vaccination. After challenge infection, repeated nasal vaccination almost completely prevented the propagation of virus in the upper and lower airways and protected cynomolgus macaques from viral pneumonia by induction of IgA-producing B cells in the lungs. On the other hand, eosinophil clusters were observed in the lungs of vaccinated macaques. Although Vac-3-specific IgE antibody and IL-13 levels were decreased after infection compared to those before infection and no anaphylaxis in vaccinated macaques was detected after challenge infection, our results suggest that we have to pay attention to potential allergic responses at repeated nasal vaccination, especially in people who have an airway allergy. (C) 2017 Elsevier Ltd. All rights reserved.