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两种人偏肺病毒候选疫苗在食蟹猴中的免疫原性和效力

Immunogenicity and efficacy of two candidate human metapneumovirus vaccines in cynomolgus macaques.

作者信息

Herfst Sander, Schrauwen Eefje J A, de Graaf Miranda, van Amerongen Geert, van den Hoogen Bernadette G, de Swart Rik L, Osterhaus Albert D M E, Fouchier Ron A M

机构信息

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

出版信息

Vaccine. 2008 Aug 5;26(33):4224-30. doi: 10.1016/j.vaccine.2008.05.052. Epub 2008 Jun 6.

Abstract

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract disease for which the development of vaccine candidates is warranted. We have previously described the generation of an iscom matrix-adjuvanted HMPV fusion protein subunit vaccine (Fsol) and a live-attenuated vaccine (HMPVM11). Here, we evaluate the immunogenicity and efficacy of these vaccines in cynomolgus macaques. Immunization with Fsol induced HMPV F-specific antibody responses, virus neutralizing antibody titers, and cellular immune responses, but the induced humoral immune response waned rapidly over time. HMPVM11 was strongly attenuated and displayed limited immunogenicity, although immunization with this virus primed for a good secondary HMPV-specific lymphoproliferative response after challenge infection. The duration of virus shedding in HMPVM11-immunized animals was reduced compared to sham-immunized animals. Both vaccines induced HMPV-specific immune responses, but the rapid waning of immunity is a challenging obstacle for vaccine development.

摘要

人偏肺病毒(HMPV)是急性呼吸道疾病的一个重要病因,因此有必要研发候选疫苗。我们之前已经描述了一种iscom基质佐剂化的HMPV融合蛋白亚单位疫苗(Fsol)和一种减毒活疫苗(HMPVM11)的构建。在此,我们评估了这些疫苗在食蟹猴中的免疫原性和效力。用Fsol免疫可诱导HMPV F特异性抗体反应、病毒中和抗体滴度和细胞免疫反应,但诱导的体液免疫反应会随时间迅速减弱。HMPVM11的毒力大幅减弱且免疫原性有限,不过用该病毒免疫可在攻毒感染后引发良好的二次HMPV特异性淋巴细胞增殖反应。与假免疫动物相比,HMPVM11免疫动物的病毒 shedding 持续时间缩短。两种疫苗都诱导了HMPV特异性免疫反应,但免疫快速减弱是疫苗研发面临的一个具有挑战性的障碍。

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