Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the co...Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants(below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-riskinfants, lowers the burden of RSV infection in certain carefully selected patient groups.展开更多
Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken ...Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken to assess the preventive effect of vaccine on RSV infection. In this metaanalysis, 1,792 published randomized clinical trials of RSV vaccines from Jan 1973 to Sep 2015 were examined. Among thirteen studies that met the inclusion criteria, eleven studies estimated the impact of RSV vaccines and four studies estimated the effect of adjuvants. The odds ratios(ORs) were 0.31(95% CI, 0.15–0.67) and 0.62(95% CI, 0.29–1.34), respectively. We found that RSV subunit vaccines can significantly reduce the incidence of RSV infection and that whether vaccination with adjuvant therapy was an effective strategy still remained to be studied. This analysis of the preventive effect of vaccines on RSV infection has direct applications for the prevention of RSV infections.展开更多
Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated re...Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.展开更多
Respiratory syncytial virus （RSV） is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children. Efficacious vaccination has been a l...Respiratory syncytial virus （RSV） is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children. Efficacious vaccination has been a longstanding goal in neonates. Due to immaturity of the neonatal immune system, vaccination has shown limited success in stimulating the neonatal endogenous immune system. Advances in the understanding of neonatal immunology have resulted in renewed development of neonatal vaccination. In this article, we review recent advances in neonatal anti- RSV vaccination strategies, including active and passive vaccination approaches, with emphasis on the effect of maternal neutralizing antibody and the role of maternal antibody in neonatal immune modulations. Recent reports in a variety of antiviral vaccine animal models have shown that maternal antibody, different from conventional vaccination, plays an immune modulatory role in the newborn immune system. Active immunization of the pregnant mother and the offspring can effectively stimulate and maintain potent neonatal immune responses, including an endogenous cytotoxic response and neutralizing antibody generation. The induced newborn endogenous antiviral immunity can last up to 6 months, and effectively blunt viral replication. Immune complexes, formed from the integral binding of the maternal neutralizing antibody and viral vaccine antigen, may play an important role in the maternal antibody-mediated neonatal immune response. The underlying mechanisms and future perspectives are discussed.展开更多
Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vacci...Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vaccinated infants upon subsequent natural RSV infection. The excessive inflammatory immunopathology in the lungs might be involved in the VED, but the underlying mechanisms remain not fully understood. In this study, we utilized UV-inactivated RSV in the prime/boost approach followed by RSV challenge in BALB/c mice to mimic RSV VED. The dynamic virus load,cytokines, histology and transcriptome profiles in lung tissues of mice were investigated from day 1 to day 6 post-infection.Compared to PBS-treated mice, UV-RSV vaccination leads to a Th2 type inflammatory response characterized by enhanced histopathology, reduced Treg cells and increased IL4^(+)CD4 T cells in the lung. Enhanced production of several Th2 type cytokines(IL-4, IL-5, IL-10) and TGF-b, reduction of IL-6 and IL-17 were observed in UV-RSV vaccinated mice. A total of 5582 differentially expressed(DE) genes between PBS-treated or vaccinated mice and na?ve mice were identified by RNA-Seq. Eleven conserved high-influential modules(HMs) were recognized, majorly grouped into regulatory networks related to cell cycle and cell metabolism, signal transduction, immune and inflammatory responses. At an early time post-infection, the vaccinated mice showed obvious decreased expression patterns of DE genes in 11 HMs compared to PBS-treated mice. The extracellular matrix(HM5) and immune responses(HM8) revealed tremendous differences in expression and regulation characteristics of transcripts between PBS-treated and vaccinated mice at both early and late time points. The highly connected genes in HM5 and HM8 networks were further validated by RT-qPCR.These findings reveal the relationship between RSV VED and immune responses, which could benefit the development of novel RSV vaccines.展开更多
Respiratory syncytial virus(RSV)poses a significant global health threat,especially affecting infants and the elderly.Addressing this,the present study proposes an innovative approach to vaccine design,utilizing immun...Respiratory syncytial virus(RSV)poses a significant global health threat,especially affecting infants and the elderly.Addressing this,the present study proposes an innovative approach to vaccine design,utilizing immunoinformatics and computational strategies.We analyzed RSV's structural proteins across both subtypes A and B,identifying potential helper T lymphocyte,cytotoxic T lymphocyte,and linear B lymphocyte epitopes.Criteria such as antigenicity,allergenicity,toxicity,and cytokine-inducing potential were rigorously examined.Additionally,we evaluated the conservancy of these epitopes and their population coverage across various RSV strains.The comprehensive analysis identified six major histocompatibility complex class I(MHC-I)binding,five MHC-II binding,and three B-cell epitopes.These were integrated with suitable linkers and adjuvants to form the vaccine.Further,molecular docking and molecular dynamics simulations demonstrated stable interactions between the vaccine candidate and human Toll-like receptors(TLR4 and TLR5),with a notable preference for TLR4.Immune simulation analysis underscored the vaccine's potential to elicit a strong immune response.This study presents a promising RSV vaccine candidate and offers theoretical support,marking a significant advancement in vaccine development efforts.However,the promising in silico findings need to be further validated through additional in vivo studies.展开更多
文摘Respiratory syncytial virus(RSV) is the most frequent and important cause of lower respiratory tract infection in infants and children. It is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. High risk groups for severe RSV disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congenital heart disease, infants with immunodeficiency or cystic fibrosis, and infants with neuromuscular diseases. Mortality rates associated with RSV infection are generally low in previous healthy infants(below 1%), but increase significantly in children with underlying chronic conditions and comorbidities. Following early RSV lower respiratory tract infection, some patients experience recurrent episodes of wheezing mimicking early childhood asthma with persistence of lung function abnormalities until adolescence. There is currently no RSV vaccine available, but promising candidate vaccines are in development. Palivizumab, a monoclonal RSV antibody that is the only tool for immunoprophylaxis in high-riskinfants, lowers the burden of RSV infection in certain carefully selected patient groups.
基金supported by grants from Natural Science Foundation of China (Grant Ref.81371797)the key project of Natural Science Research Found of Education Department of Anhui Province (Grant Ref.KJ2012A152)Natural Science Foundation of Anhui Province (Grant Ref.1308085MH129)
文摘Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken to assess the preventive effect of vaccine on RSV infection. In this metaanalysis, 1,792 published randomized clinical trials of RSV vaccines from Jan 1973 to Sep 2015 were examined. Among thirteen studies that met the inclusion criteria, eleven studies estimated the impact of RSV vaccines and four studies estimated the effect of adjuvants. The odds ratios(ORs) were 0.31(95% CI, 0.15–0.67) and 0.62(95% CI, 0.29–1.34), respectively. We found that RSV subunit vaccines can significantly reduce the incidence of RSV infection and that whether vaccination with adjuvant therapy was an effective strategy still remained to be studied. This analysis of the preventive effect of vaccines on RSV infection has direct applications for the prevention of RSV infections.
基金This work was supported by grants from the Natural Science Foundation of China(81771777,32070922).
文摘Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.
文摘Respiratory syncytial virus （RSV） is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children. Efficacious vaccination has been a longstanding goal in neonates. Due to immaturity of the neonatal immune system, vaccination has shown limited success in stimulating the neonatal endogenous immune system. Advances in the understanding of neonatal immunology have resulted in renewed development of neonatal vaccination. In this article, we review recent advances in neonatal anti- RSV vaccination strategies, including active and passive vaccination approaches, with emphasis on the effect of maternal neutralizing antibody and the role of maternal antibody in neonatal immune modulations. Recent reports in a variety of antiviral vaccine animal models have shown that maternal antibody, different from conventional vaccination, plays an immune modulatory role in the newborn immune system. Active immunization of the pregnant mother and the offspring can effectively stimulate and maintain potent neonatal immune responses, including an endogenous cytotoxic response and neutralizing antibody generation. The induced newborn endogenous antiviral immunity can last up to 6 months, and effectively blunt viral replication. Immune complexes, formed from the integral binding of the maternal neutralizing antibody and viral vaccine antigen, may play an important role in the maternal antibody-mediated neonatal immune response. The underlying mechanisms and future perspectives are discussed.
基金This work was supported by the National key R&D program of China(2017YFA0505801)the National Natural Science Foundation of China(11831015)。
文摘Respiratory syncytial virus(RSV) is the major cause of lower respiratory tract infections in children. Inactivated RSV vaccine was developed in the late 1960’s, but the vaccine-enhanced disease(VED) occurred to vaccinated infants upon subsequent natural RSV infection. The excessive inflammatory immunopathology in the lungs might be involved in the VED, but the underlying mechanisms remain not fully understood. In this study, we utilized UV-inactivated RSV in the prime/boost approach followed by RSV challenge in BALB/c mice to mimic RSV VED. The dynamic virus load,cytokines, histology and transcriptome profiles in lung tissues of mice were investigated from day 1 to day 6 post-infection.Compared to PBS-treated mice, UV-RSV vaccination leads to a Th2 type inflammatory response characterized by enhanced histopathology, reduced Treg cells and increased IL4^(+)CD4 T cells in the lung. Enhanced production of several Th2 type cytokines(IL-4, IL-5, IL-10) and TGF-b, reduction of IL-6 and IL-17 were observed in UV-RSV vaccinated mice. A total of 5582 differentially expressed(DE) genes between PBS-treated or vaccinated mice and na?ve mice were identified by RNA-Seq. Eleven conserved high-influential modules(HMs) were recognized, majorly grouped into regulatory networks related to cell cycle and cell metabolism, signal transduction, immune and inflammatory responses. At an early time post-infection, the vaccinated mice showed obvious decreased expression patterns of DE genes in 11 HMs compared to PBS-treated mice. The extracellular matrix(HM5) and immune responses(HM8) revealed tremendous differences in expression and regulation characteristics of transcripts between PBS-treated and vaccinated mice at both early and late time points. The highly connected genes in HM5 and HM8 networks were further validated by RT-qPCR.These findings reveal the relationship between RSV VED and immune responses, which could benefit the development of novel RSV vaccines.
基金The authors are thankful to the Research Institute of Agriculture and Life Sciences,Seoul National University,and the BK21 FOUR Program of the Department of Agricultural Biotechnology,Seoul National University,Seoul,Republic of Korea,for supporting the research workThis research was supported by a fund(Project Code No.Z-1543082-2019-20-01)by Research of Animal and Plant Quarantine Agency,Republic of Korea.
文摘Respiratory syncytial virus(RSV)poses a significant global health threat,especially affecting infants and the elderly.Addressing this,the present study proposes an innovative approach to vaccine design,utilizing immunoinformatics and computational strategies.We analyzed RSV's structural proteins across both subtypes A and B,identifying potential helper T lymphocyte,cytotoxic T lymphocyte,and linear B lymphocyte epitopes.Criteria such as antigenicity,allergenicity,toxicity,and cytokine-inducing potential were rigorously examined.Additionally,we evaluated the conservancy of these epitopes and their population coverage across various RSV strains.The comprehensive analysis identified six major histocompatibility complex class I(MHC-I)binding,five MHC-II binding,and three B-cell epitopes.These were integrated with suitable linkers and adjuvants to form the vaccine.Further,molecular docking and molecular dynamics simulations demonstrated stable interactions between the vaccine candidate and human Toll-like receptors(TLR4 and TLR5),with a notable preference for TLR4.Immune simulation analysis underscored the vaccine's potential to elicit a strong immune response.This study presents a promising RSV vaccine candidate and offers theoretical support,marking a significant advancement in vaccine development efforts.However,the promising in silico findings need to be further validated through additional in vivo studies.
