Roles of adjuvant and route of vaccination in antibody response and protection engendered by a synthetic matrix protein 2-based influenza A virus vaccine in the mouse.
Roles of adjuvant and route of vaccination in antibody response and protection engendered by a synthetic matrix protein 2-based influenza A virus vaccine in the mouse.
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佐剂和疫苗接种途径在小鼠体内基于合成基质蛋白 2 的甲型流感病毒疫苗产生的抗体反应和保护中的作用。
DOI：
10.1186/1743-422x-4-118
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发表时间：
2007-10-31
期刊：
影响因子：
4.8
通讯作者：
Gerhard W
中科院分区：
文献类型：
--
作者：
Mozdzanowska K;Zharikova D;Cudic M;Otvos L;Gerhard W
在过去90年中在人类中传播的甲型流感病毒（IAV）毒株的M2外结构域（M2e）显示出非常少的结构多样性。由于m2e特异性抗体（Abs）能够限制IAV在体内的复制，但在人血清中仅以最低浓度存在，因此正在努力开发m2e特异性疫苗。我们正在探索一种合成多抗原肽（MAP）疫苗，并在此报告佐剂（霍乱毒素和免疫刺激寡脱氧核苷酸）和免疫途径对Ab反应和保护强度的作用。与佐剂和免疫途径无关，平均87%的M2e- map诱导的抗体是M2e肽特异性的，这些M2e（pep）特异性抗体的可变部分（平均15%）与m2转染细胞表达的可能是天然的M2e交叉反应。经肠外免疫小鼠血清中交叉反应性M2e（pep-nat）特异性抗体滴度与保护水平呈s型关系，EC50为~20 μg Ab/ml，但经被动M2e（pep-nat）抗体实验表明，血清抗体不能完全解释肠外免疫小鼠的保护作用，特别是在上呼吸道。鼻内疫苗接种产生更强的保护和更高比例的G2a抗体，并且保护强度与M2e（pep-nat）特异性血清抗体滴度不相关，提示气道相关免疫在鼻内疫苗接种小鼠的保护中起作用。鼻内注射不加佐剂的M2e- map没有产生应答，但与感染性IAV联合使用比单独接种IAV或佐剂M2e- map稍微增强了M2e(pep-nat) Ab应答和保护作用。M2e-MAP是一种有效的免疫原，约15%的M2e-MAP诱导的抗体反应具有所需的特异性。虽然M2e（pep-nat）特异性血清抗体在限制病毒在气管和肺中的复制方面具有重要作用，但M2e特异性T细胞和/或局部产生的抗体有助于上呼吸道的保护。鼻内接种比肠外接种更可取，可能是因为前者可诱导局部保护性免疫。鉴于M2e-MAP与传染性IAV鼻内共给药在人减毒IAV疫苗接种中的潜在适用性，值得进一步研究。
The M2 ectodomain (M2e) of influenza A virus (IAV) strains that have circulated in humans during the past 90 years shows remarkably little structural diversity. Since M2e-specific antibodies (Abs) are capable of restricting IAV replication in vivo but are present only at minimal concentration in human sera, efforts are being made to develop a M2e-specific vaccine. We are exploring a synthetic multiple antigenic peptide (MAP) vaccine and here report on the role of adjuvants (cholera toxin and immunostimulatory oligodeoxynucleotide) and route of immunization on Ab response and strength of protection. Independent of adjuvants and immunization route, on average 87% of the M2e-MAP-induced Abs were specific for M2e peptide and a variable fraction of these M2e(pep)-specific Abs (average 15%) cross-reacted with presumably native M2e expressed by M2-transfected cells. The titer of these cross-reactive M2e(pep-nat)-specific Abs in sera of parenterally immunized mice displayed a sigmoidal relation to level of protection, with EC50 of ~20 μg Ab/ml serum, though experiments with passive M2e(pep-nat) Abs indicated that serum Abs did not fully account for protection in parenterally vaccinated mice, particularly in upper airways. Intranasal vaccination engendered stronger protection and a higher proportion of G2a Abs than parenteral vaccination, and the strength of protection failed to correlate with M2e(pep-nat)-specific serum Ab titers, suggesting a role of airway-associated immunity in protection of intranasally vaccinated mice. Intranasal administration of M2e-MAP without adjuvant engendered no response but coadministration with infectious IAV slightly enhanced the M2e(pep-nat) Ab response and protection compared to vaccination with IAV or adjuvanted M2e-MAP alone. M2e-MAP is an effective immunogen as ~15% of the total M2e-MAP-induced Ab response is of desired specificity. While M2e(pep-nat)-specific serum Abs have an important role in restricting virus replication in trachea and lung, M2e-specific T cells and/or locally produced Abs contribute to protection in upper airways. Intranasal vaccination is preferable to parenteral vaccination, presumably because of induction of local protective immunity by the former route. Intranasal coadministration of M2e-MAP with infectious IAV merits further investigation in view of its potential applicability to human vaccination with live attenuated IAV.