{"title":"冷适配 MERS-CoV 减毒活疫苗株在 37 °C的 Vero 细胞中多次传代后,在小鼠体内仍能保持减毒作用。","authors":"Heejeong Seo, Yunyueng Jang","doi":"10.1007/s00203-024-04120-2","DOIUrl":null,"url":null,"abstract":"<div><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease affecting camels and humans. The live attenuated vaccine represents a candidate human vaccine because it can induce strong immune responses in immunized hosts. The attenuated vaccine strain of the highly pathogenic virus can also be used to produce a cell-based vaccine in the BSL2 GMP facility. In this study, we evaluated the reversion potential of pathogenicity to pathogenic wild-type virus to ensure the safety of the live attenuated vaccine strain. We passaged our previously developed cold-adapted live attenuated MERS-CoV vaccine strain at 22 °C (EMC2012-CA22°C<b>)</b> in Vero cells at 37 °C as often as 15 times to determine the potential of pathogenicity reversion in hDPP4 (human dipeptidyl peptidase 4)-transgenic mice, K18-hDPP4. The serial passage of EMC2012-CA22°C in Vero cells at 37 °C up to 15 times did not result in pathogenicity reversion to wild-type MERS-CoV. In K18-hDPP4 mice infected with this virus, no weight loss or mortality was observed, and no virus was detected in tissues such as the lung, kidney, brain, and nasal turbinate. In addition, mice immunized with this virus produced a robust neutralizing antibody response and were fully protected from lethal challenge with wild-type MERS-CoV. The cold-adapted attenuated MERS-CoV vaccine strain (EMC2012-CA22°C) was not reverted to wild-type pathogenic virus after 15 passages in Vero cells at 37 °C.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"206 10","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cold-adapted live attenuated MERS-CoV vaccine strain remains attenuated in mice after multiple passages in Vero cells at 37 °C\",\"authors\":\"Heejeong Seo, Yunyueng Jang\",\"doi\":\"10.1007/s00203-024-04120-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease affecting camels and humans. The live attenuated vaccine represents a candidate human vaccine because it can induce strong immune responses in immunized hosts. The attenuated vaccine strain of the highly pathogenic virus can also be used to produce a cell-based vaccine in the BSL2 GMP facility. In this study, we evaluated the reversion potential of pathogenicity to pathogenic wild-type virus to ensure the safety of the live attenuated vaccine strain. We passaged our previously developed cold-adapted live attenuated MERS-CoV vaccine strain at 22 °C (EMC2012-CA22°C<b>)</b> in Vero cells at 37 °C as often as 15 times to determine the potential of pathogenicity reversion in hDPP4 (human dipeptidyl peptidase 4)-transgenic mice, K18-hDPP4. The serial passage of EMC2012-CA22°C in Vero cells at 37 °C up to 15 times did not result in pathogenicity reversion to wild-type MERS-CoV. In K18-hDPP4 mice infected with this virus, no weight loss or mortality was observed, and no virus was detected in tissues such as the lung, kidney, brain, and nasal turbinate. In addition, mice immunized with this virus produced a robust neutralizing antibody response and were fully protected from lethal challenge with wild-type MERS-CoV. The cold-adapted attenuated MERS-CoV vaccine strain (EMC2012-CA22°C) was not reverted to wild-type pathogenic virus after 15 passages in Vero cells at 37 °C.</p></div>\",\"PeriodicalId\":8279,\"journal\":{\"name\":\"Archives of Microbiology\",\"volume\":\"206 10\",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Microbiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00203-024-04120-2\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Microbiology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s00203-024-04120-2","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
中东呼吸综合征冠状病毒(MERS-CoV)是一种影响骆驼和人类的人畜共患疾病。减毒活疫苗是一种候选人类疫苗,因为它能在免疫宿主中诱导强烈的免疫反应。高致病性病毒的减毒疫苗株也可用于在 BSL2 GMP 设备中生产细胞疫苗。在本研究中,我们评估了致病性野生型病毒的致病性恢复潜力,以确保减毒活疫苗株的安全性。我们将之前开发的低温适应性 MERS-CoV 减毒活疫苗株(EMC2012-CA22°C)在 37 °C 的 Vero 细胞中传代 15 次,以确定在 hDPP4(人二肽基肽酶 4)转基因小鼠 K18-hDPP4 中致病性逆转的可能性。在 Vero 细胞中将 EMC2012-CA22°C 在 37 °C下连续培养 15 次,并未导致致病性逆转为野生型 MERS-CoV。在感染这种病毒的 K18-hDPP4 小鼠中,没有观察到体重减轻或死亡,在肺、肾、脑和鼻甲等组织中也没有检测到病毒。此外,用这种病毒免疫的小鼠产生了强大的中和抗体反应,在面对野生型 MERS-CoV 的致命挑战时完全不受影响。冷适应减毒的 MERS-CoV 疫苗株(EMC2012-CA22°C)在 37 °C的 Vero 细胞中经过 15 次传代后,并没有恢复成野生型致病病毒。
Cold-adapted live attenuated MERS-CoV vaccine strain remains attenuated in mice after multiple passages in Vero cells at 37 °C
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease affecting camels and humans. The live attenuated vaccine represents a candidate human vaccine because it can induce strong immune responses in immunized hosts. The attenuated vaccine strain of the highly pathogenic virus can also be used to produce a cell-based vaccine in the BSL2 GMP facility. In this study, we evaluated the reversion potential of pathogenicity to pathogenic wild-type virus to ensure the safety of the live attenuated vaccine strain. We passaged our previously developed cold-adapted live attenuated MERS-CoV vaccine strain at 22 °C (EMC2012-CA22°C) in Vero cells at 37 °C as often as 15 times to determine the potential of pathogenicity reversion in hDPP4 (human dipeptidyl peptidase 4)-transgenic mice, K18-hDPP4. The serial passage of EMC2012-CA22°C in Vero cells at 37 °C up to 15 times did not result in pathogenicity reversion to wild-type MERS-CoV. In K18-hDPP4 mice infected with this virus, no weight loss or mortality was observed, and no virus was detected in tissues such as the lung, kidney, brain, and nasal turbinate. In addition, mice immunized with this virus produced a robust neutralizing antibody response and were fully protected from lethal challenge with wild-type MERS-CoV. The cold-adapted attenuated MERS-CoV vaccine strain (EMC2012-CA22°C) was not reverted to wild-type pathogenic virus after 15 passages in Vero cells at 37 °C.
期刊介绍:
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