Hepatitis B(HB) virus(HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, is endemic worldwide. Hepatitis B vaccines became commercially available in the 1980 s. The World Health Organization re...Hepatitis B(HB) virus(HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, is endemic worldwide. Hepatitis B vaccines became commercially available in the 1980 s. The World Health Organization recommended the integration of the HB vaccine into the national immunisation programs in all countries. HBV prevention strategies are classified into three groups:(1) universal vaccination alone;(2) universal vaccination with screening of pregnant women plus HB immune globulin(HBIG) at birth; and(3) selective vaccination with screening of pregnant women plus HBIG at birth. Most low-income countries have adopted universal vaccine programs without screening of pregnant women. However, HB vaccines are not widely used in low-income countries. The Global Alliance for Vaccine and Immunization was launched in 2000, and by 2012, the global coverage of a three-dose HB vaccine had increased to 79%. The next challenges are to further increase the coverage rate, close the gap between recommendations and routine practices, approach highrisk individuals, screen and treat chronically infected individuals, and prevent breakthrough infections. To eradicate HBV infections, strenuous efforts are required to overcome socioeconomic barriers to the HB vaccine; this task is expected to take several decades to complete.展开更多
Background Immunization is a cornerstone of public health.Despite great success,China’s National Immunization Program(NIP)faces challenges,such as the integration of several World Health Organization-recommended vacc...Background Immunization is a cornerstone of public health.Despite great success,China’s National Immunization Program(NIP)faces challenges,such as the integration of several World Health Organization-recommended vaccines and other systemic issues.The Innovation Laboratory for Vaccine Delivery Research(VaxLab),supported by the Bill&Melinda Gates Foundation and established in 2021 at Duke Kunshan University,focuses on enhancing China’s NIP through research and policy advocacy.This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda.Key findings The collection contains eleven manuscripts discussing China’s immunization landscape and strategies to improve coverage,particularly for non-NIP vaccines like human papillomavirus vaccine(HPV),pneumococcal conjugate vaccine(PCV),Haemophilus influenzae type b vaccine(Hib),and rotavirus vaccines.Key findings include:(i)The COVID-19 vaccination campaign demonstrated China’s capacity for rapid,large-scale immunization efforts,suggesting potential for broader vaccine coverage improvements;(ii)Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access;(iii)The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles;(iv)Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage,especially for remote areas and marginalized populations;(v)Original studies emphasize the influence of caregivers’knowledge,health workers’financial incentives,and concerns about vaccine efficacy on immunization rates;(vi)Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support.Conclusion The articles emphasize the need for governmen展开更多
为研究有效的通用流感疫苗,解决流感疫苗株定期更换的难题。本课题利用乙肝病毒核心抗原（Hepatitis B core atigen,HBcAg）蛋白可以形成病毒样颗粒（Virus like larticle,VLP）的特点,将高致病性人禽流感A/Hubei/1/2010（H5N1）HA2的76...为研究有效的通用流感疫苗,解决流感疫苗株定期更换的难题。本课题利用乙肝病毒核心抗原（Hepatitis B core atigen,HBcAg）蛋白可以形成病毒样颗粒（Virus like larticle,VLP）的特点,将高致病性人禽流感A/Hubei/1/2010（H5N1）HA2的76~130氨基酸（Amino acid,AA）线性保守区（Linear conserved rgion,LCR）与HBcAg融合表达,并对其进行免疫学评价。其结果显示,优化后的LCR-HBc片段能够在pET30a大肠杆菌原核表达系统中大量表达。将纯化后的融合蛋白免疫小鼠,发现LCR-HBc疫苗组H5N1血凝素（Hemoglutination,HA）特异性IgG抗体滴度可达到1∶12 800以上。对免疫后小鼠的A/PR/8/34（PR8）致死剂量攻毒实验结果显示,LCR-HBc疫苗组肺病毒载量显著低于对照组（P〈0.01）,对小鼠的保护率为50%。本研究的开展为流感通用型疫苗的研制提供科学线索。展开更多
New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for univ...New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.展开更多
Current influenza vaccines need to be updated annually owing to constant antigenic drift in the globular head of the viral surface hemagglutinin(HA)glycoprotein.The immunogenic subdominant stem domain of HA is highly ...Current influenza vaccines need to be updated annually owing to constant antigenic drift in the globular head of the viral surface hemagglutinin(HA)glycoprotein.The immunogenic subdominant stem domain of HA is highly conserved and can be recognized by antibodies capable of binding multiple HA subtypes.Therefore,the HA stem antigen is a promising target for the design of universal influenza vaccines.On the basis of an established lipid nanoparticle-encapsulated mRNA vaccine platform,we designed and developed a novel universal influenza mRNA vaccine(mHAs)encoding the HA stem antigen of the influenza A(H1N1)virus.We tested the efficacy of the mHAs vaccine using a mouse model.The vaccine induced robust humoral and specific cellular immune responses against the stem region of HA.Importantly,two doses of the mHAs vaccine fully protected mice from lethal challenges of the heterologous H1N1 and heterosubtypic H5N8 influenza viruses.Vacci-nated mice had less pathological lung damage and lower viral titers than control mice.These results suggest that an mRNA vaccine using the conserved stem region of HA may provide effective protection against seasonal and other possible influenza variants.展开更多
COVID-19 is caused by the SARS-CoV-2 virus. Current RNA vaccines Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 are more than 94% successful in preventing infection. The spike protein of the virus is essential f...COVID-19 is caused by the SARS-CoV-2 virus. Current RNA vaccines Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 are more than 94% successful in preventing infection. The spike protein of the virus is essential for the interaction and internalization of the virus in the host cell and is considered a prime target for vaccine development against the SARS virus. This study aims to identify highly conserved sequences in spike protein or other sections of the viral genome that can potentially be used to develop a universal coronavirus vaccine. Bioinformatic analysis of 258,269 full-length SARS-CoV-2 genomic sequences in the NCBI database was carried out using a custom Perl Script. All sequences were compared to the spike protein and full-length viral genome reference to find 100 nucleotide-long segments that were at least 99% conserved across SARS-CoV-2 sequences. The analysis resulted in a >99.5% conserved 114-nucleotide segment on the spike protein and a 99.49% conserved 104-nucleotide segment on the non-spike protein section of the viral genome. The conserved sequences from this study may be useful in developing an RNA or protein vaccine that may be effective against future SARS-CoV-2 strains or could act as a universal vaccine if these sequences are present in other coronavirus families.展开更多
Currently,the incorporation of multiple epitopes into vaccines is more desirable than the incorporation of a single antigen for universal influenza vaccine development.However,epitopes induce poor immune responses.Alt...Currently,the incorporation of multiple epitopes into vaccines is more desirable than the incorporation of a single antigen for universal influenza vaccine development.However,epitopes induce poor immune responses.Although the use of adjuvants can overcome this obstacle,it may raise new problems.Effective antigen delivery vehicles that can function as both antigen carriers and intrinsic adjuvants are highly desired for vaccine development.Here,we report a biepitope nanovaccine that provides complete protection in mice against H3N2 virus as well as partial protection against H1N1 virus.This vaccine(3MCD-f)consists of two conserved epitopes(matrix protein 2 ectodomain(M2e)and CDhelix),and these epitopes were presented on the surface of ferritin in a sequential tandem format.Subcutaneous immunization with 3MCD-f in the absence of adjuvant induces robust humoral and cellular immune responses.These results provide a proof of concept for the 3MCD-f nanovaccine that might be an ideal candidate for future influenza pandemics.展开更多
甲型流感病毒基质蛋白2胞外功能区(matrix protein 2 ectodomain,M2e)通用疫苗的确切保护机制尚未明确,但其能减轻流感症状,抑制病毒的复制、存活和传播.通过使用M2e四聚体通用疫苗、M2e病毒样颗粒疫苗以及M2e多表位通用疫苗联合佐剂等...甲型流感病毒基质蛋白2胞外功能区(matrix protein 2 ectodomain,M2e)通用疫苗的确切保护机制尚未明确,但其能减轻流感症状,抑制病毒的复制、存活和传播.通过使用M2e四聚体通用疫苗、M2e病毒样颗粒疫苗以及M2e多表位通用疫苗联合佐剂等,可提高保护效果,未来具有较大的应用价值.此文通过收集相关文献资料、结合临床实践以及相关动物实验等,综述甲型流感病毒M2e通用疫苗的研究现状、免疫机制及其特点,以期为相关研究提供理论基础.展开更多
文摘Hepatitis B(HB) virus(HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, is endemic worldwide. Hepatitis B vaccines became commercially available in the 1980 s. The World Health Organization recommended the integration of the HB vaccine into the national immunisation programs in all countries. HBV prevention strategies are classified into three groups:(1) universal vaccination alone;(2) universal vaccination with screening of pregnant women plus HB immune globulin(HBIG) at birth; and(3) selective vaccination with screening of pregnant women plus HBIG at birth. Most low-income countries have adopted universal vaccine programs without screening of pregnant women. However, HB vaccines are not widely used in low-income countries. The Global Alliance for Vaccine and Immunization was launched in 2000, and by 2012, the global coverage of a three-dose HB vaccine had increased to 79%. The next challenges are to further increase the coverage rate, close the gap between recommendations and routine practices, approach highrisk individuals, screen and treat chronically infected individuals, and prevent breakthrough infections. To eradicate HBV infections, strenuous efforts are required to overcome socioeconomic barriers to the HB vaccine; this task is expected to take several decades to complete.
文摘Background Immunization is a cornerstone of public health.Despite great success,China’s National Immunization Program(NIP)faces challenges,such as the integration of several World Health Organization-recommended vaccines and other systemic issues.The Innovation Laboratory for Vaccine Delivery Research(VaxLab),supported by the Bill&Melinda Gates Foundation and established in 2021 at Duke Kunshan University,focuses on enhancing China’s NIP through research and policy advocacy.This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda.Key findings The collection contains eleven manuscripts discussing China’s immunization landscape and strategies to improve coverage,particularly for non-NIP vaccines like human papillomavirus vaccine(HPV),pneumococcal conjugate vaccine(PCV),Haemophilus influenzae type b vaccine(Hib),and rotavirus vaccines.Key findings include:(i)The COVID-19 vaccination campaign demonstrated China’s capacity for rapid,large-scale immunization efforts,suggesting potential for broader vaccine coverage improvements;(ii)Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access;(iii)The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles;(iv)Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage,especially for remote areas and marginalized populations;(v)Original studies emphasize the influence of caregivers’knowledge,health workers’financial incentives,and concerns about vaccine efficacy on immunization rates;(vi)Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support.Conclusion The articles emphasize the need for governmen
文摘为研究有效的通用流感疫苗,解决流感疫苗株定期更换的难题。本课题利用乙肝病毒核心抗原（Hepatitis B core atigen,HBcAg）蛋白可以形成病毒样颗粒（Virus like larticle,VLP）的特点,将高致病性人禽流感A/Hubei/1/2010（H5N1）HA2的76~130氨基酸（Amino acid,AA）线性保守区（Linear conserved rgion,LCR）与HBcAg融合表达,并对其进行免疫学评价。其结果显示,优化后的LCR-HBc片段能够在pET30a大肠杆菌原核表达系统中大量表达。将纯化后的融合蛋白免疫小鼠,发现LCR-HBc疫苗组H5N1血凝素（Hemoglutination,HA）特异性IgG抗体滴度可达到1∶12 800以上。对免疫后小鼠的A/PR/8/34（PR8）致死剂量攻毒实验结果显示,LCR-HBc疫苗组肺病毒载量显著低于对照组（P〈0.01）,对小鼠的保护率为50%。本研究的开展为流感通用型疫苗的研制提供科学线索。
文摘New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.
基金supported by the Key Collaborative Research Program of the 14 Alliance of International Science Organ-izations(Grant No.ANSO‐CR‐SP‐2020‐05)the National Natural Science Foundation of China(Grant No.32170068).
文摘Current influenza vaccines need to be updated annually owing to constant antigenic drift in the globular head of the viral surface hemagglutinin(HA)glycoprotein.The immunogenic subdominant stem domain of HA is highly conserved and can be recognized by antibodies capable of binding multiple HA subtypes.Therefore,the HA stem antigen is a promising target for the design of universal influenza vaccines.On the basis of an established lipid nanoparticle-encapsulated mRNA vaccine platform,we designed and developed a novel universal influenza mRNA vaccine(mHAs)encoding the HA stem antigen of the influenza A(H1N1)virus.We tested the efficacy of the mHAs vaccine using a mouse model.The vaccine induced robust humoral and specific cellular immune responses against the stem region of HA.Importantly,two doses of the mHAs vaccine fully protected mice from lethal challenges of the heterologous H1N1 and heterosubtypic H5N8 influenza viruses.Vacci-nated mice had less pathological lung damage and lower viral titers than control mice.These results suggest that an mRNA vaccine using the conserved stem region of HA may provide effective protection against seasonal and other possible influenza variants.
文摘COVID-19 is caused by the SARS-CoV-2 virus. Current RNA vaccines Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 are more than 94% successful in preventing infection. The spike protein of the virus is essential for the interaction and internalization of the virus in the host cell and is considered a prime target for vaccine development against the SARS virus. This study aims to identify highly conserved sequences in spike protein or other sections of the viral genome that can potentially be used to develop a universal coronavirus vaccine. Bioinformatic analysis of 258,269 full-length SARS-CoV-2 genomic sequences in the NCBI database was carried out using a custom Perl Script. All sequences were compared to the spike protein and full-length viral genome reference to find 100 nucleotide-long segments that were at least 99% conserved across SARS-CoV-2 sequences. The analysis resulted in a >99.5% conserved 114-nucleotide segment on the spike protein and a 99.49% conserved 104-nucleotide segment on the non-spike protein section of the viral genome. The conserved sequences from this study may be useful in developing an RNA or protein vaccine that may be effective against future SARS-CoV-2 strains or could act as a universal vaccine if these sequences are present in other coronavirus families.
基金the National Natural Science Foundation of China(No.31770996).
文摘Currently,the incorporation of multiple epitopes into vaccines is more desirable than the incorporation of a single antigen for universal influenza vaccine development.However,epitopes induce poor immune responses.Although the use of adjuvants can overcome this obstacle,it may raise new problems.Effective antigen delivery vehicles that can function as both antigen carriers and intrinsic adjuvants are highly desired for vaccine development.Here,we report a biepitope nanovaccine that provides complete protection in mice against H3N2 virus as well as partial protection against H1N1 virus.This vaccine(3MCD-f)consists of two conserved epitopes(matrix protein 2 ectodomain(M2e)and CDhelix),and these epitopes were presented on the surface of ferritin in a sequential tandem format.Subcutaneous immunization with 3MCD-f in the absence of adjuvant induces robust humoral and cellular immune responses.These results provide a proof of concept for the 3MCD-f nanovaccine that might be an ideal candidate for future influenza pandemics.
文摘甲型流感病毒基质蛋白2胞外功能区(matrix protein 2 ectodomain,M2e)通用疫苗的确切保护机制尚未明确,但其能减轻流感症状,抑制病毒的复制、存活和传播.通过使用M2e四聚体通用疫苗、M2e病毒样颗粒疫苗以及M2e多表位通用疫苗联合佐剂等,可提高保护效果,未来具有较大的应用价值.此文通过收集相关文献资料、结合临床实践以及相关动物实验等,综述甲型流感病毒M2e通用疫苗的研究现状、免疫机制及其特点,以期为相关研究提供理论基础.
