Human immune responses elicited by an intranasal inactivated H5 influenza vaccine
Human immune responses elicited by an intranasal inactivated H5 influenza vaccine
复制标题
DOI：
10.1111/1348-0421.12775
复制
发表时间：
2020-03-29
影响因子：
2.6
通讯作者：
Hasegawa, Hideki
中科院分区：
文献类型：
--
作者：
Ainai, Akira;van Riet, Elly;Hasegawa, Hideki
鼻内接种流感疫苗可能比注射疫苗更有效，因为鼻内接种可在上呼吸道（感染的初始部位）诱导病毒特异性免疫球蛋白A（伊加）抗体。在这项研究中，在未感染过甲型流感（H5N1）病毒的健康个体中评价了甲型流感（H5N1）病毒鼻内灭活疫苗引起的免疫应答。三剂鼻内灭活H5全病毒体流感疫苗诱导了强中和性鼻伊加和血清IgG抗体。此外，粘膜粘附赋形剂羧基乙烯基聚合物对鼻伊加抗体应答的诱导有显著影响，但对血清IgG抗体应答无显著影响。鼻血凝素（HA）特异性伊加抗体反应与粘膜中和抗体反应明显相关，表明鼻HA特异性伊加滴度的测量可用作粘膜抗体反应的替代。此外，疫苗接种后观察到外周血中浆细胞和疫苗抗原特异性Th细胞数量增加，这表明外周血生物标志物也可用于评估鼻内疫苗诱导的免疫反应。然而，外周血免疫细胞应答与血清样本中的中和抗体滴度相关，但与鼻洗液样本中的中和抗体滴度无关。因此，外周血免疫应答的分析可以替代对鼻内接种的全身免疫应答，但不能替代粘膜免疫应答。目前的研究表明，鼻内灭活疫苗对甲型流感（H5N1）病毒的临床潜力，并强调需要开发新的手段来评估鼻内疫苗诱导的粘膜免疫反应。
Intranasally administered influenza vaccines could be more effective than injected vaccines, because intranasal vaccination can induce virus-specific immunoglobulin A (IgA) antibodies in the upper respiratory tract, which is the initial site of infection. In this study, immune responses elicited by an intranasal inactivated vaccine of influenza A(H5N1) virus were evaluated in healthy individuals naive for influenza A(H5N1) virus. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy vinyl polymer, had a notable impact on the induction of nasal IgA antibody responses but not on serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific Th cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against influenza A(H5N1) viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses.