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用人偏肺病毒F亚基疫苗免疫叙利亚金黄地鼠可诱导产生针对同源或异源毒株攻击的保护作用。

Immunization of Syrian golden hamsters with F subunit vaccine of human metapneumovirus induces protection against challenge with homologous or heterologous strains.

作者信息

Herfst Sander, de Graaf Miranda, Schrauwen Eefje J A, Ulbrandt Nancy D, Barnes Arnita S, Senthil Kannaki, Osterhaus Albert D M E, Fouchier Ron A M, van den Hoogen Bernadette G

机构信息

Department of Virology, Erasmus MC, Rotterdam, The Netherlands.

MedImmune, Inc., 1 MedImmune Way, Gaithersburg, MD 20878, USA.

出版信息

J Gen Virol. 2007 Oct;88(Pt 10):2702-2709. doi: 10.1099/vir.0.83084-0.

Abstract

Human metapneumovirus (hMPV), a newly discovered paramyxovirus, is associated with acute respiratory-tract illness, primarily in young children, individuals with underlying disease and the elderly. Two genetic lineages of hMPV circulate around the world, and viruses from these two lineages demonstrate antigenic differences. The clinical impact of hMPV warrants the development of vaccines. Recombinant soluble fusion (F) proteins of prototype viruses of the two main lineages of hMPV that can be produced in high yields have been constructed. In this study, the antigenicity, immunogenicity and protective efficacy of these soluble F subunit vaccines were evaluated in Syrian golden hamsters (Mesocricetus auratus). Immunization of hamsters with the soluble F proteins, adjuvanted with Specol or iscom matrix, induced high virus-neutralization titres, with higher titres against the homologous than the heterologous virus. The neutralizing antibodies protected from subsequent infection of the lungs with both homologous and heterologous virus. Upon challenge, viral titres in the nasal turbinates of immunized animals were reduced significantly compared with those of PBS-immunized animals. In conclusion, a soluble F subunit vaccine for hMPV that induces cross-protective immunity for infection of the lower respiratory tract in Syrian golden hamsters has been generated.

摘要

人偏肺病毒(hMPV)是一种新发现的副粘病毒,主要与急性呼吸道疾病相关,多见于幼儿、患有基础疾病的个体及老年人。hMPV的两个基因谱系在全球传播,来自这两个谱系的病毒表现出抗原差异。hMPV对临床的影响使得疫苗的研发成为必要。已构建出可高产的hMPV两个主要谱系原型病毒的重组可溶性融合(F)蛋白。在本研究中,在叙利亚金黄地鼠(Mesocricetus auratus)中评估了这些可溶性F亚基疫苗的抗原性、免疫原性和保护效力。用佐剂Specol或iscom基质的可溶性F蛋白免疫仓鼠可诱导出高病毒中和滴度,对同源病毒的滴度高于对异源病毒的滴度。中和抗体可保护仓鼠免受同源和异源病毒随后的肺部感染。在攻毒后,与用PBS免疫的动物相比,免疫动物鼻甲中的病毒滴度显著降低。总之,已研制出一种可诱导叙利亚金黄地鼠对下呼吸道感染产生交叉保护性免疫的hMPV可溶性F亚基疫苗。

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