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二价嵌合病毒样颗粒和 DNA 疫苗共免疫诱导小鼠产生有前景的体液免疫应答。

Co-Immunization With CHIKV VLP and DNA Vaccines Induces a Promising Humoral Response in Mice.

机构信息

National Health Commission (NHC) Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.

Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Zhejiang, China.

出版信息

Front Immunol. 2021 Mar 24;12:655743. doi: 10.3389/fimmu.2021.655743. eCollection 2021.

Abstract

Chikungunya fever is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV), for which no licensed vaccines are currently available. Here, we explored several immunization protocols and investigated their immunity and protective effects in mice, with DNA- and virus-like particle (VLP)- vaccines, both alone and in combination. Both DNA and VLP vaccine candidates were developed and characterized, which express CHIKV structural genes (C-E3-E2-6K-E1). Mice were immunized twice, with different protocols, followed by immunological detection and CHIKV Ross challenge. The highest antigen-specific IgG and neutralizing activity were induced by DNA and VLP co-immunization, while the highest cellular immunity was induced by DNA vaccination alone. Although all vaccine groups could protect mice from lethal CHIKV challenge, demonstrated as reduced viral load in various tissues, without weight loss, mice co-immunized with DNA and VLP exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. We concluded that co-immunization with DNA and VLP is a promising strategy to inducing better protective immunity against CHIKV infection.

摘要

基孔肯雅热是一种由蚊媒传播的基孔肯雅病毒(CHIKV)引起的急性传染病,目前尚无许可的疫苗。在这里,我们探索了几种免疫方案,并在小鼠中研究了它们的免疫原性和保护作用,包括 DNA 疫苗和病毒样颗粒(VLP)疫苗,以及单独使用和联合使用。我们开发并表征了表达 CHIKV 结构基因(C-E3-E2-6K-E1)的 DNA 和 VLP 疫苗候选物。小鼠接受了两次免疫,采用不同的方案,然后进行免疫学检测和 CHIKV Ross 挑战。DNA 和 VLP 联合免疫诱导了最高的抗原特异性 IgG 和中和活性,而单独的 DNA 疫苗接种诱导了最高的细胞免疫。虽然所有疫苗组都能保护小鼠免受致死性 CHIKV 挑战,表现为各种组织中的病毒载量降低,体重无减轻,但与单独使用 DNA 或 VLP 疫苗接种的小鼠相比,DNA 和 VLP 联合免疫的小鼠表现出最轻微的组织病理学变化和最低的国际命名和诊断标准(INHAND)评分。我们得出结论,DNA 和 VLP 的联合免疫是诱导针对 CHIKV 感染更好保护免疫的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/520d/8044884/2f80b3440819/fimmu-12-655743-g001.jpg

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