中文摘要：鼻内免疫禽流感疫苗能够诱导局部呼吸道粘膜产生病毒特异性IgA抗体，提高机体IgA抗体浓度。本研究组已有的研究表明，采用灭活H3N2或H5N1疫苗进行鼻内免疫后，机体上呼吸道内IgA抗体呈单体、二聚体和多聚体（三聚体和四聚体）形式。多聚体的病毒中和活性最高。本研究采用2倍剂量的鼻内三聚体灭活流感病毒对供试者进行免疫，结果发现鼻腔洗液中多聚体IgA抗体与病毒中和滴度相关，表明多聚体IgA抗体在鼻黏膜抗病毒活性过程中发挥重要作用。对源于鼻洗液的IgA抗体单体、二聚体和多聚体抗重组三联流感病毒HA的活性进行等离子表面共振分析，结果表明：包含IgA抗体多聚体的浓缩样本中HA的解离程度略优于不含IgA抗体多聚体的浓缩样本。因此，IgA抗体多聚体与抗原结合的紧密度高于其他结构。总而言之，鼻内免疫双剂量多价灭活禽流感疫苗会诱导产生IgA抗体多聚体。粘膜IgA抗体的多聚化提高了抗原抗体的黏合，从而提高了鼻黏膜抗病毒中和活性。
 
外文摘要：Unlike the current injectable influenza vaccines, intranasally administered influenza vaccines induce influenza virus-specific IgA antibodies in the local respiratory mucosa as well as IgG antibodies in the systemic circulation. Our previous study showed that after five volunteers underwent intranasal administration with inactivated H3N2 or H5N1 vaccines, their IgA antibodies on the upper respiratory tract were present as monomers, dimers, and multimers (trimers and tetramers). Moreover, the multimers associated with the highest virus neutralizing activity. However, it has remained elusive whether a more practical intranasal vaccination strategy could induce the high-performance IgA multimers in the nasal mucosa. In the present study, volunteers were administered with two doses of the intranasal trivalent whole-virus inactivated influenza vaccine and showed that in nasal wash samples the amount of multimeric IgA correlated positively with virus neutralizing titers, indicating that the multimeric IgA antibodies play an important role in the antiviral activity at the nasal mucosa. Surface plasmon resonance analysis of the binding dynamics of nasal wash derived IgA monomers, dimers, and multimers against recombinant trimeric influenza virus HA showed that sample fractions containing IgA multimers dissociated from HA less well than sample fractions without IgA multimers. Thus, IgA multimers may stick to the antigen more tightly than the other structures. In summary, intranasal administration of two doses of multivalent inactivated influenza vaccines induced multimeric IgA. Multimerization of mucosal IgA antibodies conferred higher neutralizing activity against viruses in the nasal mucosa, possibly by increasing their cohesion to virus antigens.
 
外文关键词：Secretory IgA antibody； multimeric SIgA antibody； influenza virus； intranasal inactivated influenza vaccine； upper respiratory mucosa
作者：Terauchi, Y；Sano, K；Ainai, A；Saito, S；Taga, Y；Ogawa-Goto, K；Tamura, S；Odagiri, T；Tashiro, M；Fujieda, M；Suzuki, T；Hasegawa, H
作者单位：日本国立传染病研究所
期刊名称：HUMAN VACCINES & IMMUNOTHERAPEUTICS
期刊影响因子：2.229
出版年份：2018
出版刊次：6
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