Development of recombinant rotavirus carrying herpes simplex virus 2 glycoprotein D gene based on reverse genetics technology

IF 1.9 4区 医学 Q4 IMMUNOLOGY Microbiology and Immunology Pub Date : 2023-12-14 DOI:10.1111/1348-0421.13107
Yoshiki Kawamura, Satoshi Komoto, Saori Fukuda, Masanori Kugita, Shuang Tang, Amita Patel, Julianna R. Pieknik, Shizuko Nagao, Koki Taniguchi, Philip R. Krause, Tetsushi Yoshikawa
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Abstract

Vaccine development for herpes simplex virus 2 (HSV-2) has been attempted, but no vaccines are yet available. A plasmid-based reverse genetics system for Rotavirus (RV), which can cause gastroenteritis, allows the generation of recombinant RV containing foreign genes. In this study, we sought to develop simian RV (SA11) as a vector to express HSV-2 glycoprotein D (gD2) and evaluated its immunogenicity in mice. We generated the recombinant SA11-gD2 virus (rSA11-gD2) and confirmed its ability to express gD2 in vitro. The virus was orally inoculated into suckling BALB/c mice and into 8-week-old mice. Serum IgG and IgA titers against RV and gD2 were measured by ELISA. In the 8-week-old mice inoculated with rSA11-gD2, significant increases in not only antibodies against RV but also IgG against gD2 were demonstrated. In the suckling mice, antibodies against RV were induced, but gD2 antibody was not detected. Diarrhea observed after the first inoculation of rSA11-gD2 in suckling mice was similar to that induced by the parent virus. A gD2 expressing simian RV recombinant, which was orally inoculated, induced IgG against gD2. This strategy holds possibility for genital herpes vaccine development.

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基于反向遗传学技术开发携带单纯疱疹病毒 2 糖蛋白 D 基因的重组轮状病毒
针对单纯疱疹病毒 2(HSV-2)的疫苗开发工作已经开始,但目前还没有疫苗问世。轮状病毒(Rotavirus,RV)可引起肠胃炎,而基于质粒的反向遗传学系统可产生含有外来基因的重组 RV。在本研究中,我们试图开发猿猴 RV(SA11)作为表达 HSV-2 糖蛋白 D(gD2)的载体,并在小鼠体内评估其免疫原性。我们生成了重组 SA11-gD2 病毒(rSA11-gD2),并在体外证实了其表达 gD2 的能力。我们将病毒口服接种到哺乳的 BALB/c 小鼠和 8 周大的小鼠体内。用酶联免疫吸附法测定血清中针对 RV 和 gD2 的 IgG 和 IgA 滴度。在接种了 rSA11-gD2 的 8 周龄小鼠中,不仅针对 RV 的抗体显著增加,而且针对 gD2 的 IgG 也显著增加。在乳鼠中,RV抗体被诱导出来,但没有检测到gD2抗体。乳鼠首次接种 rSA11-gD2 后观察到的腹泻与母体病毒诱导的腹泻相似。口服表达 gD2 的猿 RV 重组病毒可诱导出针对 gD2 的 IgG。这一策略为生殖器疱疹疫苗的开发提供了可能。
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来源期刊
Microbiology and Immunology
Microbiology and Immunology 医学-免疫学
CiteScore
5.20
自引率
3.80%
发文量
78
审稿时长
1 months
期刊介绍: Microbiology and Immunology is published in association with Japanese Society for Bacteriology, Japanese Society for Virology, and Japanese Society for Host Defense Research. It is peer-reviewed publication that provides insight into the study of microbes and the host immune, biological and physiological responses. Fields covered by Microbiology and Immunology include:Bacteriology|Virology|Immunology|pathogenic infections in human, animals and plants|pathogenicity and virulence factors such as microbial toxins and cell-surface components|factors involved in host defense, inflammation, development of vaccines|antimicrobial agents and drug resistance of microbes|genomics and proteomics.
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