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流感反向遗传学疫苗种子:以PB1来源作为病毒生长和抗原产量的决定因素的概念验证

Reverse genetics vaccine seeds for influenza: Proof of concept in the source of PB1 as a determinant factor in virus growth and antigen yield.

作者信息

Gíria Marta, Santos Luís, Louro João, Rebelo de Andrade Helena

机构信息

Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Av Gama Pinto 1649-003 Lisboa, Portugal.

Host-Pathogen Interaction Unit, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Av Gama Pinto 1649-003 Lisboa, Portugal; Departamento de Doenças Infecciosas, Instituto Nacional de Saúde Dr Ricardo Jorge IP, Av Padre Cruz 1649-016 Lisboa, Portugal.

出版信息

Virology. 2016 Sep;496:21-27. doi: 10.1016/j.virol.2016.05.015. Epub 2016 May 27.

Abstract

Growth deficits of reverse genetics vaccine seeds have compromised effective immunization. The impairment has been attributed to sub-optimal protein interactions. Some level of dependence may exist between PB1 and antigenic glycoproteins, however, further research is necessary to clarify the extent to which it can be used in favor of seed production. Our objective was to establish proof of concept on the phenotypic outcome of PB1 source in the PR8: A(H1N1)pdm09 reassortants. Reassortants were generated with the gene constellation of the classical 6:2 PR8: HA, NApdm09 seed prototype and the 5:3 reassortant PR8: HA, NA, PB1pdm09. Viral growth and antigen yield were evaluated 12-60h post-infection. The 5:3 reassortant presented statistically significant growth and antigen yield improvements when compared to the 6:2. We believe these findings to be of promising value to vaccine research towards an improvement of reverse genetic seeds, an overall more cost-effective vaccine manufacture and timely delivery.

摘要

反向遗传学疫苗种子的生长缺陷影响了有效免疫。这种损害归因于次优的蛋白质相互作用。PB1与抗原糖蛋白之间可能存在一定程度的依赖性,然而,需要进一步研究以阐明其在何种程度上可用于支持种子生产。我们的目标是建立关于PB1来源在PR8:A(H1N1)pdm09重配体中的表型结果的概念验证。使用经典的6:2 PR8:HA、NApdm09种子原型和5:3重配体PR8:HA、NA、PB1pdm09的基因组合产生重配体。在感染后12 - 60小时评估病毒生长和抗原产量。与6:2相比,5:3重配体在生长和抗原产量方面有统计学上显著的提高。我们认为这些发现对于疫苗研究具有潜在价值,有助于改进反向遗传种子,实现总体上更具成本效益的疫苗生产和及时交付。

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