Attenuated MuV-S79 as vector stably expressing foreign gene

Zhou, Duo; Zhu, Man; Wang, Yilong; Hao, Xiaoqiang; Zhou, Dongming; Rong-xian, Liu; Zhang, Chu-di; Qu, Chu-Fan; Zhao, Zhengyan

doi:10.1007/s12519-019-00287-7

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…This method has been approved in other studies for rescue of human metapneumovirus, bovine respiratory syncytial virus and measles virus (Ma et al 2014;Sun et al 2014;Zhang et al 2014;Cui et al 2017;Pang et al 2018;Wang et al 2018;Zhou et al 2019b). We have effectively rescued rMuV-S79 without helper vaccinia virus in our previous researches (Zhou et al 2019a(Zhou et al , 2019b.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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. Electronic supplementary material The online version of this article (10.1007/s12250-020-00326-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…The ability to manipulate MuV genome by reverse genetics systems has been used as a tool (a) for investigation of MuV biology [14][15][16][17][18][19][20][21], (b) for optimization of a mumps vaccine [22], and (c) to investigate possibilities of using MuV as a vector in recombinant vaccines or in gene therapy [4,[23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Population Variability Generated during Rescue Process and Passaging of Recombinant Mumps Viruses

Slović

Košutić-Gulija

Forčić

et al. 2021

Viruses

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Recombinant mumps viruses (MuVs) based on established vaccine strains represent attractive vector candidates as they have known track records for high efficacy and the viral genome does not integrate in the host cells. We developed a rescue system based on the consensus sequence of the L-Zagreb vaccine and generated seven different recombinant MuVs by (a) insertion of one or two additional transcription units (ATUs), (b) lengthening of a noncoding region to the extent that the longest noncoding region in MuV genome is created, or (c) replacement of original L-Zagreb sequences with sequences rich in CG and AT dinucleotides. All viruses were successfully rescued and faithfully matched sequences of input plasmids. In primary rescued stocks, low percentages of heterogeneous positions were found (maximum 0.12%) and substitutions were predominantly obtained in minor variants, with maximally four substitutions seen in consensus. ATUs did not accumulate more mutations than the natural MuV genes. Six substitutions characteristic for recombinant viruses generated in our system were defined, as they repetitively occurred during rescue processes. In subsequent passaging of primary rescue stocks in Vero cells, different inconsistencies within quasispecies structures were observed. In order to assure that unwanted mutations did not emerge and accumulate, sub-consensus variability should be closely monitored. As we show for Pro408Leu mutation in L gene and a stop codon in one of ATUs, positively selected variants can rise to frequencies over 85% in only few passages.

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A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway

Zhang

Wang

Zhou

et al. 2021

Translational Oncology

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Attenuated MuV-S79 as vector stably expressing foreign gene

Cited by 3 publications

References 19 publications

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

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

Population Variability Generated during Rescue Process and Passaging of Recombinant Mumps Viruses

A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway

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