A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose.
A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose.
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DOI：
10.1016/j.vaccine.2012.03.035
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发表时间：
2012-05-21
期刊：
影响因子：
5.5
通讯作者：
Harmsen, Allen G.
中科院分区：
文献类型：
--
作者：
Richert, Laura E.;Servid, Amy E.;Harmsen, Ann L.;Rynda-Apple, Agnieszka;Han, Soo;Wiley, James A.;Douglas, Trevor;Harmsen, Allen G.
我们将OVA与sHsp纳米颗粒结合，并显示其用于疫苗接种的实用性。结论OVA-sHsp免疫小鼠，免疫应答迅速，免疫强度高。次给药结束OVA-sHsp的递送导致与sHsp本身相同的对OVA的免疫应答。Hsp在肺中起佐剂作用，并诱导粘膜伊加的产生。sHsp预处理提供了对流感的保护性抗体和细胞应答。我们表明，模型抗原，卵清蛋白（OVA），可以化学结合到外部的一个小的热休克蛋白（sHsp）笼，具有结构相似的病毒样颗粒（VLP）。OVA-sHsp缀合效率取决于所用小分子接头的化学计量和长度以及sHsp笼上的连接位置。当将缀合的OVA-sHsp鼻内递送至未处理小鼠时，所产生的对OVA的免疫应答被加速和加强，并且在单次免疫剂量后的5天内，OVA特异性IgG 1应答是明显的，这说明了其用于疫苗开发的效用。如果在OVA-sHsp缀合物免疫之前用不同的VLP P22（非复制性噬菌体衣壳）预处理动物，则在单次免疫剂量的缀合物后4天，OVA-特异性IgG 1应答在OVA-未处理小鼠中已经明显。此外，用P22预处理的小鼠产生高滴度的粘膜伊加和同种型转换的OVA特异性血清IgG。同样，sHsp预处理增强了肺生发中心B细胞、T滤泡辅助细胞的积累，并增加了多聚IG受体的表达，从而引发了肺对流感病毒攻击的后续IgG和伊加反应。因此，sHsp纳米颗粒引起快速和强烈的抗体应答，并且这些加速的应答可以类似地被化学缀合至sHsp的抗原诱导。用P22预处理小鼠进一步加速了对OVA-sHsp的抗体应答的开始，证明了将抗原缀合至VLP用于肺的暴露前或可能暴露后预防的效用，所有这些都不需要佐剂。
► We conjugated OVA to a sHsp nanoparticle, and show its utility for vaccination. ► The immune response to OVA–sHsp was quick and intense with a single i.n. dose. ► Delivery of OVA–sHsp resulted in the same immune response to OVA as sHsp itself. ► sHsp acted as an adjuvant in the lungs, and induced the production of mucosal IgA. ► Pre-treatment with sHsp provided protective ab and cellular responses to influenza. We show that a model antigen, ovalbumin (OVA), can be chemically conjugated to the exterior of a small heat shock protein (sHsp) cage that has structural similarities to virus-like particles (VLPs). OVA–sHsp conjugation efficiency was dependent upon the stoichiometry and the length of the small molecule linker utilized, and the attachment position on the sHsp cage. When conjugated OVA–sHsp was delivered intranasally to naïve mice, the resulting immune response to OVA was accelerated and intensified, and OVA-specific IgG1 responses were apparent within 5 days after a single immunizing dose, illustrating its utility for vaccine development. If animals were pretreated with a disparate VLP, P22 (a non-replicative bacteriophage capsid), before OVA–sHsp conjugate immunization, OVA-specific IgG1 responses were apparent already by 4 days after a single immunizing dose of conjugate in OVA-naïve mice. Additionally, the mice pretreated with P22 produced high titer mucosal IgA, and isotype-switched OVA-specific serum IgG. Similarly, sHsp pretreatment enhanced the accumulation of lung germinal center B cells, T follicular helper cells, and increased polymeric Ig receptor expression, priming the lungs for subsequent IgG and IgA responses to influenza virus challenge. Thus, sHsp nanoparticles elicited quick and intense antibody responses and these accelerated responses could similarly be induced to antigen chemically conjugated to the sHsp. Pretreatment of mice with P22 further accelerated the onset of the antibody response to OVA–sHsp, demonstrating the utility of conjugating antigens to VLPs for pre-, or possibly post-exposure prophylaxis of lung, all without the need for adjuvant.
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影响因子：
5.5
作者：
Jegerlehner, A;Tissot, A;Bachmann, MF
通讯作者：
Bachmann, MF
影响因子：
5.5
作者：
Huang, Z;Elkin, G;Mason, HS
通讯作者：
Mason, HS
DOI：
10.1186/1476-8518-8-1
发表时间：
2010-02-04
期刊：
Journal of immune based therapies and vaccines
影响因子：
--
作者：
Bhagawati-Prasad, Vijay Ns;De Leenheer, Evy;Heath, Andrew W
通讯作者：
Heath, Andrew W
影响因子：
6.4
作者：
Acosta-Ramirez, Elizabeth;Perez-Flores, Rebeca;Lopez-Macias, Constantino
通讯作者：
Lopez-Macias, Constantino
影响因子：
10.8
作者：
Flenniken, ML;Willits, DA;Douglas, T
通讯作者：
Douglas, T