Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administratio...Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administration has the advantage of being needle free and self-administered,thereby improving compliance and coverage of large populations.In China,the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy.The hurdles we are facing in the development of mucosal vaccines,however,come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines.Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration,not only at the scientific level but,most importantly,by engaging public and private health organizations,governments,and regulatory authorities.We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.展开更多
Chronic hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). While multiple treatment modalities are available, liver transplantation remains the sole curative treatment for adv...Chronic hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). While multiple treatment modalities are available, liver transplantation remains the sole curative treatment for advanced stages of HCC, and hence new treatment approaches are required to fulfill this unmet need of curative HCC therapy. Our first-in-man proof-of-concept adoptive T-cell immunotherapy against HBV related hepatocellular carcinoma metastases has shown promising results. Here, we review the development of T-cell immunotherapy targeting HBV antigens for the treatment of HBV-HCC and discuss the practical considerations for the safe and effective use in clinics.展开更多
Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype ...Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype having a better response.ITPA gene deficiency protects against clinically significant anaemia induced by treatment.The purpose of this study was to determine IL28B polymorphismand ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response(SVR).Methods:All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study.Blood samples for IL28B and ITPA genotyping were obtained.Medical records were reviewed for verification of treatment response,development of anaemia and if treatment reduction was required during the treatment.Results:A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin,of whom 42 agreed to participate in the study.Mean age was 45.6±12.9 years at time of treatment,and 83.3%of patients weremales.Thirty-three(78.6%)had IL28B CC genotype,of whom 25(75.8%)obtained SVR compared with only 3 of 9(33.3%)non C/C genotype patients who achieved SVR(P=0.041).Eleven(26.1%)patients had ITPA AC genotype,and 30(71.4%)had CC genotype.There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia(45.5%vs 63.3%,P=0.302).Even among patients who developed anaemia,70.8%stillmanaged to achieve SVR.Treatment reduction also had no impact on SVR.Conclusion:Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.展开更多
基金supported by the Gates Foundation(INV-059115)the Alliance of International Science Organizations(ANSO-CR-KP-2022-01)partly supported by the National Natural Science Foundation of China(92469301).
文摘Human mucosal immunization is expected to afford protection against infection and reduce transmission by generating anti-infective immunity at the mucosal entry site of viruses and bacteria.Nasal or oral administration has the advantage of being needle free and self-administered,thereby improving compliance and coverage of large populations.In China,the experience of COVID-19 has promoted substantial efforts in the development of nasal vaccinations in the general health protection strategy.The hurdles we are facing in the development of mucosal vaccines,however,come from the still limited knowledge of the mechanisms controlling mucosal immunity in different anatomical locations and in response to different pathogens/vaccines.Identifying and filling the knowledge gaps in order to develop effective and safe mucosal immunization strategies requires global collaboration,not only at the scientific level but,most importantly,by engaging public and private health organizations,governments,and regulatory authorities.We have highlighted here some of the crucial issues in mucosal immunization and provided suggestions for the way forward toward a global preparedness effort to prevent infectious diseases and ensure vaccine equity.
文摘Chronic hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). While multiple treatment modalities are available, liver transplantation remains the sole curative treatment for advanced stages of HCC, and hence new treatment approaches are required to fulfill this unmet need of curative HCC therapy. Our first-in-man proof-of-concept adoptive T-cell immunotherapy against HBV related hepatocellular carcinoma metastases has shown promising results. Here, we review the development of T-cell immunotherapy targeting HBV antigens for the treatment of HBV-HCC and discuss the practical considerations for the safe and effective use in clinics.
文摘Background and aim:Conventional hepatitis C treatment using pegylated interferon(PEG-IFN)and ribavirin is associated with significant side effects.IL28B polymorphism can predict response to treatment,with CC genotype having a better response.ITPA gene deficiency protects against clinically significant anaemia induced by treatment.The purpose of this study was to determine IL28B polymorphismand ITPA variation among hepatitis C genotype 1 patients who have undergone therapy with PEG-IFN and ribavirin and their association with sustained viral response(SVR).Methods:All hepatitis C genotype 1 patients who had been treated with PEG-IFN and ribavirin over the past 10 years were identified by available medical records and were contacted by letter of invitation to participate in the study.Blood samples for IL28B and ITPA genotyping were obtained.Medical records were reviewed for verification of treatment response,development of anaemia and if treatment reduction was required during the treatment.Results:A total of 61 patients with hepatitis C genotype 1 were treated with PEG-IFN and ribavirin,of whom 42 agreed to participate in the study.Mean age was 45.6±12.9 years at time of treatment,and 83.3%of patients weremales.Thirty-three(78.6%)had IL28B CC genotype,of whom 25(75.8%)obtained SVR compared with only 3 of 9(33.3%)non C/C genotype patients who achieved SVR(P=0.041).Eleven(26.1%)patients had ITPA AC genotype,and 30(71.4%)had CC genotype.There was no statistically significant difference between ITPA AC and CC genotypes in predicting clinically significant anaemia(45.5%vs 63.3%,P=0.302).Even among patients who developed anaemia,70.8%stillmanaged to achieve SVR.Treatment reduction also had no impact on SVR.Conclusion:Hepatitis C genotype 1 patients should be informed of the response rate for treatment with PEG-IFN and ribavirin in a population with favourable IL28B genotype before consideration of newer therapeutic options.
