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 sti...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 r MuVs 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.展开更多
Introduction:To evaluate population immunity against the mumps virus(MuV)after China’s two-dose Measles-Mumps-Rubella(MMR)vaccine policy was introduced in June 2020,we conducted a seroepidemiological analysis among i...Introduction:To evaluate population immunity against the mumps virus(MuV)after China’s two-dose Measles-Mumps-Rubella(MMR)vaccine policy was introduced in June 2020,we conducted a seroepidemiological analysis among individuals aged 0–19 years.Methods:A cross-sectional survey was conducted in Fujian Province from March to June 2023.MuV IgG antibodies were detected using ELISA,and their seroprevalence and geometric mean concentrations(GMCs)were assessed.Population immunity in 2023 was compared with a 2018 survey.Results:Overall seroprevalence and GMCs in 2023 were 79.53%and 265.61 U/mL,respectively.Both varied significantly by age:levels rose from 8 months,peaked at 2–5 years,then declined to a low point at 15–17 years.In 2023,seroprevalence and GMCs were higher in children aged 0–1 year(47.29%vs.14.51%;97.15 U/mL vs.34.13 U/mL)and lower in those 15–17 years(58.06%vs.80.73%;126.00 U/mL vs.289.98 U/mL)compared with 2018;2-year-olds showed higher GMCs(554.85 U/mL vs.353.39 U/mL).Among vaccinated individuals,antibody levels peaked 15–90 days after the latest vaccination;twodose recipients exhibited significantly higher antibody levels than one-dose recipients within 270 days.Conclusions:China’s two-dose MMR vaccine policy has effectively increased seroprevalence and GMCs in children 8 months-2 years.Continuous monitoring of antibody decline is essential,particularly for those aged 6–19 years with weaker immunity.展开更多
基金supported by The National Natural Science Foundation for Young Scholars of China (81901679)The Natural Science Foundation for Young Scholars of Zhejiang Province (LQ19H100005)China Postdoctoral Science Foundation (2019M662076)。
文摘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 r MuVs 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.
基金Supported by the Talent Training Project of Fujian Provincial Health Commission(2021GGB011).
文摘Introduction:To evaluate population immunity against the mumps virus(MuV)after China’s two-dose Measles-Mumps-Rubella(MMR)vaccine policy was introduced in June 2020,we conducted a seroepidemiological analysis among individuals aged 0–19 years.Methods:A cross-sectional survey was conducted in Fujian Province from March to June 2023.MuV IgG antibodies were detected using ELISA,and their seroprevalence and geometric mean concentrations(GMCs)were assessed.Population immunity in 2023 was compared with a 2018 survey.Results:Overall seroprevalence and GMCs in 2023 were 79.53%and 265.61 U/mL,respectively.Both varied significantly by age:levels rose from 8 months,peaked at 2–5 years,then declined to a low point at 15–17 years.In 2023,seroprevalence and GMCs were higher in children aged 0–1 year(47.29%vs.14.51%;97.15 U/mL vs.34.13 U/mL)and lower in those 15–17 years(58.06%vs.80.73%;126.00 U/mL vs.289.98 U/mL)compared with 2018;2-year-olds showed higher GMCs(554.85 U/mL vs.353.39 U/mL).Among vaccinated individuals,antibody levels peaked 15–90 days after the latest vaccination;twodose recipients exhibited significantly higher antibody levels than one-dose recipients within 270 days.Conclusions:China’s two-dose MMR vaccine policy has effectively increased seroprevalence and GMCs in children 8 months-2 years.Continuous monitoring of antibody decline is essential,particularly for those aged 6–19 years with weaker immunity.
