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Development of Improved Mumps Vaccine Candidates by Mutating Viral mRNA Cap Methyltransferase Sites in the Large Polymerase Protein.

التفاصيل البيبلوغرافية
العنوان: Development of Improved Mumps Vaccine Candidates by Mutating Viral mRNA Cap Methyltransferase Sites in the Large Polymerase Protein.
المؤلفون: Hao X; Zhejiang University School of Medicine, Hangzhou, 310058, China., Wang Y; The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China., Zhu M; Zhejiang University School of Medicine, Hangzhou, 310058, China., Zhou D; The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China., Liu R; Zhejiang University School of Medicine, Hangzhou, 310058, China., Wang B; Institute of Preventive Veterinary Medicine and Key Laboratory of Animal Virology of Ministry of Agriculture, Department of Veterinary Medicine, Zhejiang University, Hangzhou, 310058, China., Huang YW; Institute of Preventive Veterinary Medicine and Key Laboratory of Animal Virology of Ministry of Agriculture, Department of Veterinary Medicine, Zhejiang University, Hangzhou, 310058, China. yhuang@zju.edu.cn., Zhao Z; Zhejiang University School of Medicine, Hangzhou, 310058, China. Zhaozy@zju.edu.cn.; The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, China. Zhaozy@zju.edu.cn.
المصدر: Virologica Sinica [Virol Sin] 2021 Jun; Vol. 36 (3), pp. 521-536. Date of Electronic Publication: 2020 Dec 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V. on behalf of KeAi Communications Co. Ltd Country of Publication: Netherlands NLM ID: 101514185 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1995-820X (Electronic) Linking ISSN: 1995820X NLM ISO Abbreviation: Virol Sin Subsets: MEDLINE
أسماء مطبوعة: Publication: 2022- : [Amsterdam, Netherlands] : Elsevier B.V. on behalf of KeAi Communications Co. Ltd.
Original Publication: Beijing : Science Press
مواضيع طبية MeSH: Methyltransferases*/genetics , Mumps Vaccine*, China ; Mumps virus/genetics ; Mumps virus/immunology ; RNA, Messenger/genetics
مستخلص: Although a live attenuated vaccine is available for controlling mumps virus (MuV), mumps still outbreaks frequently worldwide. The attenuated MuV vaccine strain S79 is widely used in mumps vaccination in China, but still with many shortcomings, among which the most prominent are the side effects and decreased immunity. Therefore, there is a need to further improve the safety and efficacy of the current MuV vaccine. In the present study, we further attenuated MuV S79 vaccine strain by inhibiting viral mRNA methyltransferase (MTase). We generated a panel of eight recombinant MuVs (rMuVs) carrying mutations in the MTase catalytic site or S-adenosylmethionine (SAM) binding site in the large (L) polymerase protein. These rMuVs are genetically stable and seven rMuVs are more attenuated in replication in cell culture and five rMuVs are more attenuated in replication in lungs of cotton rats compared with the parental vaccine strain S79. Importantly, cotton rats vaccinated with these seven rMuV mutants produced high levels of serum neutralizing antibodies and were completely protected against challenge with a wild-type MuV strain (genotype F). Therefore, our results demonstrate that alteration in the MTase catalytic site or SAM binding site in MuV L protein improves the safety or the immunogenicity of the MuV vaccine and thus mRNA cap MTase may be an effective target for the development of new vaccine candidates for MuV.
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فهرسة مساهمة: Keywords: Large polymerase protein; Methyltransferase (MTase); Mumps virus (MuV); Vaccine
المشرفين على المادة: 0 (Mumps Vaccine)
0 (RNA, Messenger)
EC 2.1.1.- (Methyltransferases)
تواريخ الأحداث: Date Created: 20201207 Date Completed: 20211005 Latest Revision: 20211005
رمز التحديث: 20240513
مُعرف محوري في PubMed: PMC7719854
DOI: 10.1007/s12250-020-00326-y
PMID: 33284397
قاعدة البيانات: MEDLINE
الوصف
تدمد:1995-820X
DOI:10.1007/s12250-020-00326-y