Vaccination has played a crucial role in combating infectious diseases for human and has made significant contributions to global public health.Successful vaccination has eradicated many life-threatening diseases,such...Vaccination has played a crucial role in combating infectious diseases for human and has made significant contributions to global public health.Successful vaccination has eradicated many life-threatening diseases,such as smallpox and polio[1].The World Health Organization estimates that vaccines can prevent 2–3 million deaths from tetanus,pertussis,influenza,and measles annually.展开更多
Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation be...Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic exponential decay model.The potential effect of thimerosal on protein function,particularly for thiolcontaining proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.展开更多
Monoclonal antibody （mAb）-based therapeutics are playing an increasingly important role in the treatment or pre- vention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Mul...Monoclonal antibody （mAb）-based therapeutics are playing an increasingly important role in the treatment or pre- vention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multi- domain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-trans- lational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase as well as post licensure life cycle managemenL Specially, the molecular characteriza- tion, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parame- ters and the methods used for obtaining them. The three groups of analytical methods are three essential and inte. gral facets making up the whole analytical package for a mAIPbased drug. Such a package is critically important for the licensure and the post-licensurs life cycle management of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilar mAbs were discussed briefly based on the recommendations by the World Health Organization.展开更多
The 2016 Lasker-DeBakey Clinical Medical Research Award was given to three scientists working on different stages of the translational sciences on bringing a high efficacious therapy against hepatitis C virus （HCV） ...The 2016 Lasker-DeBakey Clinical Medical Research Award was given to three scientists working on different stages of the translational sciences on bringing a high efficacious therapy against hepatitis C virus （HCV） infection to a reality. An effective treatment of HCV chronic infection was developed, by a team led by Michael Sofia, using a prodrug approach and the drug PSI-7977 or Sofosbuvir was approved in 2013 less than 28 years after the initial discovery of HCV.展开更多
Background:The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines pre‑sent a dilemma in vaccination choices,which may result in individuals refusing a particular COVID-19 va...Background:The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines pre‑sent a dilemma in vaccination choices,which may result in individuals refusing a particular COVID-19 vaccine ofered,hence presenting a threat to immunisation coverage and reaching herd immunity.The study aimed to assess global COVID-19 vaccination intention,vaccine characteristics infuencing vaccination acceptance and desirable vaccine characteristics infuencing the choice of vaccines.Methods:An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 coun‑tries worldwide.Proportions and the corresponding 95%confdence intervals(CI)of COVID-19 vaccine acceptance and vaccine characteristics infuencing vaccination acceptance were generated and compared across countries and regions.Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy.Results:Of the 19,714 responses received,90.4%(95%CI 81.8–95.3)reported likely or extremely likely to receive COVID-19 vaccine.A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia(96.4%),China(95.3%)and Norway(95.3%),while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan(34.6%),the U.S.(29.4%)and Iran(27.9%).Males,those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy.Less than two-thirds(59.7%;95%CI 58.4–61.0)reported only being willing to accept a vaccine with an efectiveness of more than 90%,and 74.5%(95%CI 73.4–75.5)said they would accept a COVID-19 vaccine with minor adverse reactions.A total of 21.0%(95%CI 20.0–22.0)reported not accepting an mRNA vaccine and 51.8%(95%CI 50.3–53.1)reported that they would only accept a COVID-19 vaccine from a specifc country‐of‐origin.Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology.The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries.The foremost important vaccine characteristic infuencing vaccine choice is adverse reactions(40.6%;95%CI 39.3–41.9)of a vaccine and efectiveness threshold(35.1%;95%CI 33.9–36.4).Conclusions:The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efcient plan for the delivery of interventions dynamically tailored to the local population.展开更多
基金supported by grants from the National Natural Science Foundation of China(82371832 to X.Z.,and 81991491 to Q.Z.,)Natural Science Foundation of Chongqing City(2023NSCQ-MSX1536 to X.Z.)+1 种基金Natural Science Foundation of Fujian Province(2023J011235 to X.Z.)Chongqing Education Commission of Science and Technology Research Project(KJQN202300453 to X.Z.).
文摘Vaccination has played a crucial role in combating infectious diseases for human and has made significant contributions to global public health.Successful vaccination has eradicated many life-threatening diseases,such as smallpox and polio[1].The World Health Organization estimates that vaccines can prevent 2–3 million deaths from tetanus,pertussis,influenza,and measles annually.
基金Thisworkwas funded by the National Natural Science Foundation of China(Grant Nos.:81993149041,and U1705283)the National Science and Technology Major Project,China(Project No.:2018ZX09303005-002)+1 种基金Fujian Health Education Joint Research Project,China(Project No.:2019-WJ-05)Xiamen Science and Technology Major Project,China(Project No.:3502Z20193009).
文摘Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic exponential decay model.The potential effect of thimerosal on protein function,particularly for thiolcontaining proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.
文摘Monoclonal antibody （mAb）-based therapeutics are playing an increasingly important role in the treatment or pre- vention of many important diseases such as cancers, autoimmune disorders, and infectious diseases. Multi- domain mAbs are far more complex than small molecule drugs with intrinsic heterogeneities. The critical quality attributes of a given mAb, including structure, post-trans- lational modifications, and functions at biomolecular and cellular levels, need to be defined and profiled in details during the developmental phases of a biologics. These critical quality attributes, outlined in this review, serve an important database for defining the drug properties during commercial production phase as well as post licensure life cycle managemenL Specially, the molecular characteriza- tion, functional assessment, and effector function analysis of mAbs, are reviewed with respect to the critical parame- ters and the methods used for obtaining them. The three groups of analytical methods are three essential and inte. gral facets making up the whole analytical package for a mAIPbased drug. Such a package is critically important for the licensure and the post-licensurs life cycle management of a therapeutic or prophylactic biologics. In addition, the basic principles on the evaluation of biosimilar mAbs were discussed briefly based on the recommendations by the World Health Organization.
文摘The 2016 Lasker-DeBakey Clinical Medical Research Award was given to three scientists working on different stages of the translational sciences on bringing a high efficacious therapy against hepatitis C virus （HCV） infection to a reality. An effective treatment of HCV chronic infection was developed, by a team led by Michael Sofia, using a prodrug approach and the drug PSI-7977 or Sofosbuvir was approved in 2013 less than 28 years after the initial discovery of HCV.
文摘Background:The availability of various types of COVID-19 vaccines and diverse characteristics of the vaccines pre‑sent a dilemma in vaccination choices,which may result in individuals refusing a particular COVID-19 vaccine ofered,hence presenting a threat to immunisation coverage and reaching herd immunity.The study aimed to assess global COVID-19 vaccination intention,vaccine characteristics infuencing vaccination acceptance and desirable vaccine characteristics infuencing the choice of vaccines.Methods:An anonymous cross-sectional survey was conducted between 4 January and 5 March 2021 in 17 coun‑tries worldwide.Proportions and the corresponding 95%confdence intervals(CI)of COVID-19 vaccine acceptance and vaccine characteristics infuencing vaccination acceptance were generated and compared across countries and regions.Multivariable logistic regression analysis was used to determine the factors associated with COVID-19 vaccine hesitancy.Results:Of the 19,714 responses received,90.4%(95%CI 81.8–95.3)reported likely or extremely likely to receive COVID-19 vaccine.A high proportion of likely or extremely likely to receive the COVID-19 vaccine was reported in Australia(96.4%),China(95.3%)and Norway(95.3%),while a high proportion reported being unlikely or extremely unlikely to receive the vaccine in Japan(34.6%),the U.S.(29.4%)and Iran(27.9%).Males,those with a lower educational level and those of older age expressed a higher level of COVID-19 vaccine hesitancy.Less than two-thirds(59.7%;95%CI 58.4–61.0)reported only being willing to accept a vaccine with an efectiveness of more than 90%,and 74.5%(95%CI 73.4–75.5)said they would accept a COVID-19 vaccine with minor adverse reactions.A total of 21.0%(95%CI 20.0–22.0)reported not accepting an mRNA vaccine and 51.8%(95%CI 50.3–53.1)reported that they would only accept a COVID-19 vaccine from a specifc country‐of‐origin.Countries from the Southeast Asia region reported the highest proportion of not accepting mRNA technology.The highest proportion from Europe and the Americas would only accept a vaccine produced by certain countries.The foremost important vaccine characteristic infuencing vaccine choice is adverse reactions(40.6%;95%CI 39.3–41.9)of a vaccine and efectiveness threshold(35.1%;95%CI 33.9–36.4).Conclusions:The inter-regional and individual country disparities in COVID-19 vaccine hesitancy highlight the importance of designing an efcient plan for the delivery of interventions dynamically tailored to the local population.
