The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shor...The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.展开更多
Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced...Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced vaccine compliance and completion.Thus,it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule.This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis andHaemophilus influenzae type B conjugate(DTaP-IPV/Hib)vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations.Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023.The study employed a stratified multistage cluster random sampling method.Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire.Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations.Results Of the 4818 valid responses,95.3%of children were aged 3-4 years,and 2856(59.3%)held ruralhukou.Coverage rates of the DTaP-IPV/Hib vaccine,from 1 to 4 doses,were 24.4%,20.7%,18.5%,and 16.0%,respectively.Caregivers who are concerned about vaccine efficacy[adjusted odds ratio(aOR)=1.53,95%confidence interval(CI):1.30-1.79],the manufacturer(aOR=2.05,95%CI:1.69-2.49),and a simple immunization schedule(aOR=1.26,95%CI:1.04-1.54)are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib.In addition,caregivers in urban areas showed more concern about the vaccine price(P=0.010)and immunization schedule(P=0.022)in regard to vaccinating children.Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low.Factors such as lower socioeconomi展开更多
Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America ...Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.展开更多
Background:Communication for Development(C4D)is a strategy promoted by the United Nations Children’s Fund to foster positive and measurable changes at the individual,family,community,social,and policy levels of socie...Background:Communication for Development(C4D)is a strategy promoted by the United Nations Children’s Fund to foster positive and measurable changes at the individual,family,community,social,and policy levels of society.In western China,C4D activities have previously been conducted as part of province-level immunization programs.In this study,we evaluated the association of C4D with changes in parental knowledge of immunization services,measles disease,and measles vaccine,and changes in their children’s measles vaccine coverage.Methods:From April 2013 to April 2014,C4D activities were implemented as part of provincial immunization programs in the Inner Mongolia,Guangxi,Chongqing,Guizhou,Tibet,Shaanxi,Gansu,Ningxia,and Qinghai provinces.We used a before-and-after study design and employed face-to-face interviews to assess changes in parental knowledge and vaccination coverage.Results:We surveyed 2107 households at baseline and 2070 households after 1 year of C4D activities.Following C4D,95%of caregivers were aware of the vaccination record check requirement for entry into kindergarten and primary school;80%of caregivers were aware that migrant children were eligible for free vaccination;more than 70%of caregivers knew that measles is a respiratory infectious disease;and 90%of caregivers knew the symptoms of measles.Caregivers’willingness to take their children to the clinic for vaccination increased from 51.3%at baseline to 67.4%in the post-C4D survey.Coverage of one-dose measles-containing vaccine(MCV)increased from 83.8%at baseline to 90.1%after C4D.One-dose MCV coverage was greater than 95%in the Guangxi,Shaanxi,and Gansu provinces.Two-dose MCV coverage increased from 68.5 to 77.6%.House-to-house communication was the most popular C4D activity among caregivers(91.6%favoring),followed by posters and educational talks(64.8 and 49.9%favoring).Conclusions:C4D is associated with increased caregiver knowledge about measles,increased willingness to seek immunization services for their children,and increased measl展开更多
Hepatitis B virus(HBV)immunization is safe and has been accepted worldwide as a routine practice.The target of such vaccination is to induce the immune response in the host,resulting in the prevention of replication o...Hepatitis B virus(HBV)immunization is safe and has been accepted worldwide as a routine practice.The target of such vaccination is to induce the immune response in the host,resulting in the prevention of replication of HBV.There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine.In this article we have highlighted the response of the host immune system to HBV vaccination(immunogenicity),efficacy,and safety of the vaccine,issues with booster dosing,paths of development(preclinical and clinical)of the HBV vaccine,novel and upcoming strategies for improvement of HBV vaccination,and the concept of therapeutic HBV vaccination.The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed.The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen,increasing the antigen dose,accelerated vaccination schedules,alternative vaccination route,use of adjuvants like immunostimulatory DNA sequences,etc.Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.展开更多
Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery ...Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.展开更多
A peptide (J14) containing conformationally restricted epitopes from the M protein of group A streptococcus (GAS) is capable of eliciting protective immune response against GAS infection. However, the protective respo...A peptide (J14) containing conformationally restricted epitopes from the M protein of group A streptococcus (GAS) is capable of eliciting protective immune response against GAS infection. However, the protective response may be lost possibly due to its weak secondary-structure when the antigen is fused with other antigens in a recombinant polyepitope vaccine construct. We previously showed that JJo, a conformationally stabilized derivative of dimeric J14, overcomes this problem. We now show that anti JJo antibodies react with diverse GAS isolates found in the Indian sub-continent and that these antibodies are opsonic for GAS. The GAS strains used in this study were isolated from throat and skin swabs from Mumbai, Chennai and Vellore. Sera from mice immunized with recombinant JJo peptide were tested by ELISA, immunofluorescence, flow-cytometry, indirect bactericidal assay and mouse challenge assays to determine specific immunogenicity, opsonic functions and protection against an Indian isolate. We propose that JJo is a robust antigen suitable for inclusion in recombinant multi-epitope vaccines which are potentially affordable option for the pediatric population of developing countries.展开更多
2019年12月发生的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)对全球公共卫生造成巨大危机。世界卫生组织(World Health Organization,WHO)在2020年3月11日宣布COVID-19为全球大流行。目前,新型冠状病毒疫苗研发的技术路线主...2019年12月发生的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)对全球公共卫生造成巨大危机。世界卫生组织(World Health Organization,WHO)在2020年3月11日宣布COVID-19为全球大流行。目前,新型冠状病毒疫苗研发的技术路线主要有灭活疫苗、重组蛋白疫苗、病毒载体疫苗、核酸疫苗和减毒活疫苗,此外,还有运用反向疫苗学和疫苗组学等新兴概念进行疫苗的设计。本文对目前正在研发和临床试验的各类新型冠状病毒疫苗以及研发所面临的挑战作一综述。展开更多
文摘The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.
基金This work was supported by the Bill&Melinda Gates Foundation(Grant No.INV-049539)the Key Research and Development Program of Hainan Province(Grant No.ZDYF2020210)+1 种基金the Project of the National Social Science Fund of China(Grant No.20BGL264)the Shanghai Public Health System Construction Three-Year Action Plan(Grant No.GWVI-11.1-48)。
文摘Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced vaccine compliance and completion.Thus,it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule.This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis andHaemophilus influenzae type B conjugate(DTaP-IPV/Hib)vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations.Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023.The study employed a stratified multistage cluster random sampling method.Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire.Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations.Results Of the 4818 valid responses,95.3%of children were aged 3-4 years,and 2856(59.3%)held ruralhukou.Coverage rates of the DTaP-IPV/Hib vaccine,from 1 to 4 doses,were 24.4%,20.7%,18.5%,and 16.0%,respectively.Caregivers who are concerned about vaccine efficacy[adjusted odds ratio(aOR)=1.53,95%confidence interval(CI):1.30-1.79],the manufacturer(aOR=2.05,95%CI:1.69-2.49),and a simple immunization schedule(aOR=1.26,95%CI:1.04-1.54)are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib.In addition,caregivers in urban areas showed more concern about the vaccine price(P=0.010)and immunization schedule(P=0.022)in regard to vaccinating children.Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low.Factors such as lower socioeconomi
基金supported in part by the National Key Program Project Grant from MOST #2016YFC1201000
文摘Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.
基金The UNICEF China Office and the Fourth Round of Three-Year Public Health Action Plan of Shanghai,China(15GWZK0101)supported the C4D intervention activities,the baseline investigation,and the evaluation investigation。
文摘Background:Communication for Development(C4D)is a strategy promoted by the United Nations Children’s Fund to foster positive and measurable changes at the individual,family,community,social,and policy levels of society.In western China,C4D activities have previously been conducted as part of province-level immunization programs.In this study,we evaluated the association of C4D with changes in parental knowledge of immunization services,measles disease,and measles vaccine,and changes in their children’s measles vaccine coverage.Methods:From April 2013 to April 2014,C4D activities were implemented as part of provincial immunization programs in the Inner Mongolia,Guangxi,Chongqing,Guizhou,Tibet,Shaanxi,Gansu,Ningxia,and Qinghai provinces.We used a before-and-after study design and employed face-to-face interviews to assess changes in parental knowledge and vaccination coverage.Results:We surveyed 2107 households at baseline and 2070 households after 1 year of C4D activities.Following C4D,95%of caregivers were aware of the vaccination record check requirement for entry into kindergarten and primary school;80%of caregivers were aware that migrant children were eligible for free vaccination;more than 70%of caregivers knew that measles is a respiratory infectious disease;and 90%of caregivers knew the symptoms of measles.Caregivers’willingness to take their children to the clinic for vaccination increased from 51.3%at baseline to 67.4%in the post-C4D survey.Coverage of one-dose measles-containing vaccine(MCV)increased from 83.8%at baseline to 90.1%after C4D.One-dose MCV coverage was greater than 95%in the Guangxi,Shaanxi,and Gansu provinces.Two-dose MCV coverage increased from 68.5 to 77.6%.House-to-house communication was the most popular C4D activity among caregivers(91.6%favoring),followed by posters and educational talks(64.8 and 49.9%favoring).Conclusions:C4D is associated with increased caregiver knowledge about measles,increased willingness to seek immunization services for their children,and increased measl
文摘Hepatitis B virus(HBV)immunization is safe and has been accepted worldwide as a routine practice.The target of such vaccination is to induce the immune response in the host,resulting in the prevention of replication of HBV.There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine.In this article we have highlighted the response of the host immune system to HBV vaccination(immunogenicity),efficacy,and safety of the vaccine,issues with booster dosing,paths of development(preclinical and clinical)of the HBV vaccine,novel and upcoming strategies for improvement of HBV vaccination,and the concept of therapeutic HBV vaccination.The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed.The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen,increasing the antigen dose,accelerated vaccination schedules,alternative vaccination route,use of adjuvants like immunostimulatory DNA sequences,etc.Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.
文摘Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.
文摘A peptide (J14) containing conformationally restricted epitopes from the M protein of group A streptococcus (GAS) is capable of eliciting protective immune response against GAS infection. However, the protective response may be lost possibly due to its weak secondary-structure when the antigen is fused with other antigens in a recombinant polyepitope vaccine construct. We previously showed that JJo, a conformationally stabilized derivative of dimeric J14, overcomes this problem. We now show that anti JJo antibodies react with diverse GAS isolates found in the Indian sub-continent and that these antibodies are opsonic for GAS. The GAS strains used in this study were isolated from throat and skin swabs from Mumbai, Chennai and Vellore. Sera from mice immunized with recombinant JJo peptide were tested by ELISA, immunofluorescence, flow-cytometry, indirect bactericidal assay and mouse challenge assays to determine specific immunogenicity, opsonic functions and protection against an Indian isolate. We propose that JJo is a robust antigen suitable for inclusion in recombinant multi-epitope vaccines which are potentially affordable option for the pediatric population of developing countries.
文摘2019年12月发生的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)对全球公共卫生造成巨大危机。世界卫生组织(World Health Organization,WHO)在2020年3月11日宣布COVID-19为全球大流行。目前,新型冠状病毒疫苗研发的技术路线主要有灭活疫苗、重组蛋白疫苗、病毒载体疫苗、核酸疫苗和减毒活疫苗,此外,还有运用反向疫苗学和疫苗组学等新兴概念进行疫苗的设计。本文对目前正在研发和临床试验的各类新型冠状病毒疫苗以及研发所面临的挑战作一综述。
