Seroepidemiology of hepatitis B virus infection and impact of vaccination

AIM: To investigate hepatitis B virus(HBV) prevalence in the general population in China.METHODS: A total of 148931 individuals were investigated by multistage random sampling in Eastern China. Data were collected on demographics and hepatitis B vaccination history, and serum was tested for hepatitis B surface antigen(HBs Ag) by ELISA. RESULTS: A total of 11469 participants(7.70%, 95%CI: 7.57%-7.84%) were positive for HBs Ag. HBs Ag prevalence was 0.77% among children < 5 years old but increased progressively from adolescents(1.40%-2.55%) to adults(5.69%-11.22%). A decrease in HBs Ag prevalence was strongly associated with vaccination and familial history of HBV among both children and adult groups. Meanwhile, HBs Ag risk in adults was associated with invasive testing and sharing needles. The HBV immunization rate among participants aged < 20 years was 93.30%(95%CI: 93.01%-93.58%). Significant difference in HBs Ag prevalence appeared between vaccinated and unvaccinated participants(3.59% vs 10.22%). CONCLUSION: Although the national goal of HBs Ag prevalence < 1% among children < 5 years old has been reached, immunization programs should be maintained to prevent resurgence.

新冠病毒肺炎疫苗研制面临的挑战

1.引言由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的新型冠状病毒肺炎(COVID-19)目前已在全球大规模暴发,已成为重大的公共卫生危机事件[1]。严峻的疫情形势凸显了有效的治疗和预防方案的必要性。一些国家已经加快了开发安全有效疫苗的临床试验进程,从而遏制目前疫情的发展[2]。

Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years:a phase Ⅰ trial

Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.

Epidemiology of hepatitis C virus in Iran

In Iran,the prevalence of hepatitis C virus(HCV) infection is relatively low according to the populationbased epidemiological studies. However,the epidemiology of HCV is changing and the rate of HCV infection is increasing due to the growth in the number of injecting drug users in the society. In addition,a shift has occurred in the distribution pattern of HCV genotypes among HCV-infected patients in Iran. Genotype 1a is the most prevalent genotype in Iran,but in recent years,an increase in the frequency of 3a and a decrease in 1a and 1b have been reported. These variations in the epidemiology of HCV reflect differences in the routes of transmission,status of public health,lifestyles,and risk factors in different groups and geographic regions of Iran. Health policy makers should consider these differences to establish better strategies for control and prevention of HCV infection. Therefore,this review was conducted to present a clear view regarding the current epidemiology of HCV infection in Iran.

Molecular Epidemiology and Sequencing of the G-L Intergenic Region of Rabies Viruses Isolated in China

一组 25 个狂犬病病毒(RABV ) ，从 24 条狗和一个人的盒子恢复了，在在 2004 和 2006 之间的中国从各种各样的区域被收集。G-L intergenic 区域的基因、种系发生的分析在 25 街 RABV 被执行孤立， CTN 疫苗 7 拉紧代。学习基于 519 bp 核苷酸顺序的比较，包含 G-L intergenic 区域。中国街紧张的核苷酸顺序相同从 95.5% ～ 100% 。种系发生的分析证明中国的所有孤立清楚地在 Lyssavirus 遗传型 1 支持了所有中国病毒的放置，他们根据他们的地理起源是分布式的。所有仔细中国紧张被联系，但是他们能仍然被划分成二个组：一些街紧张和一些 CTN 紧张。这研究基于 G-L Intergenic 区域的序列关于狂犬病病毒的分子的传染病学介绍细节。关键词狂犬病病毒 - 分子的传染病学 - G-L intergenic 区域 - 中国 CLC 数字 R373.33 基础条款：第 10 国家 five-year-plan (2004BA718 b03 ) 的关键技术 R&D

Next Steps for Efficacy Evaluation in Clinical Trials of COVID-19 Vaccines

1.Introduction A vaccine clinical trial examines the effects of a vaccine on human volunteers in terms of safety,immunogenicity,and clinical efficacy through three distinct stages[1].In general,phase 1 studies focus on safety and reactogenicity,while phase 2 studies attempt to establish an immunogenicity proof of dose range,dosage,and immunization procedure(sometimes even efficacy data).Large phase 3 studies are designed to evaluate whether the dosing and vaccination schedule can deliver the desired protection efficacy with an acceptable safety profile[2].A phase 3 vaccine clinical trial provides indispensable efficacy data to support a vaccine that has been issued with licensure.

The Prevalence and Levels of Anti-HEV IgG in the Population of Jiangsu Province, China

Objective To investigate the prevalence and levels of anti-HEV IgG in the population of Jiangsu Province.Methods Total of 2 656 samples from Qindong and 11 463 samples from Anfeng were colleted.The antiHEV antibody was qualitatively and quantitatively detected using ELISA kits and the references had been established.Results The positive rates of anti-HEV IgG in male and female were 55.6%and 40.1%,respectively.The positive rate of anti-HEV IgM in male and female were both 3.4%.In opposite to anti-HEV IgG,the positive rate of anti-HEV IgM in Anfeng was significant higher than that in Qindong.The mean anti-HEV IgG titers for6 age groups were 0.94,0.92,1.07,1.46,1.27,1.19 and 0.68,1.31,1.08,1.14,1.31,1.68 IU/ml,in Qindong and Anfeng region,respectively.The positive rate of anti-HEV IgG tended to increase with age and the titer of antiHEV IgG was associated with age(R>0.90).Conclusions The results in this study showed that HEV was widely prevalent in both Qindong and Anfeng of Jiansu Province and the prevalence and the anti-HEV IgG titer were associated with gender and age.

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs.3 doses in young women

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women.A randomized,immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China.Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6(n=301)or 3 doses at months 0,1 and 6(n=304).Girls aged 15–17 years(n=149)and women aged 18–26 years(n=225)received 3 doses.The objectives included noninferiority analysis of the IgG geometric mean concentration(GMC)ratio(95%CI,lower bound>0.5)to HPV-16 and HPV-18 at month 7 in girls compared with women.In the per-protocol set,the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women(1.76(95%CI,1.56,1.99)for HPV-16 and 1.93(95%CI,1.69,2.21)for HPV-18)and noninferior for girls aged 9–14 years receiving 2 doses compared with women(1.45(95%CI,1.25,1.62)for HPV-16 and 1.17(95%CI,1.02,1.33)for HPV-18).Noninferiority was also demonstrated for neutralizing antibodies.The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials

Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).

Severe human infection with a novel avian-origin influenza A(H7N4) virus

Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient.We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets(LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry(chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.

Safety and immunogenicity of a recombinant COVID-19 vaccine(Sf9 cells)in healthy population aged 18 years or older:two single-center,randomised,double-blind,placebo-controlled,phase 1 and phase 2 trials

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply.We did two singlecenter,randomised,double-blind,placebo-controlled phase 1 and phase 2 trials to assess the safety,tolerability and immunogenicity of a recombinant COVID-19 vaccine(Sf9 cells)in healthy population aged 18 years or older in China.Eligible participants were enrolled,the ratio of candidate vaccine and placebo within each dose group was 3:1(phase 1)or 5:1(phase 2).From August 28,2020,168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine,high dose vaccine or placebo with the schedule of 0,28 days or 0,14,28 days in phase 1 trial.From November 18,2020,960 participants were randomly assigned to receive the low dose vaccine,high dose vaccine or placebo with the schedule of 0,21 days or 0;14,28 days in phase 2 trial.The most common solicited injection site adverse reaction within 7 days in both trials was pain.The most common solicited systematic adverse reactions within 7 days were fatigue,cough,sore throat,fever and headache.ELISA antibodies and neutralising antibodies increased at 14 days,and peaked at 28 days(phase 1)or 30 days(phase 2)after the last dose vaccination.The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group(0,14,28 days),with 102.9(95%Cl 61.9-171.2)and 102.6(95%Cl 75.2-140.1)in phase 1 and phase 2 trials,respectively.Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial.This vaccine is safe,and induced significant immune responses after three doses of vaccination.

Coronavirus disease 2019 vaccines:landscape of global studies and potential risks

With the outbreak of the coronavirus disease 2019(COVID-19)pandemic,the importance of vaccines in epidemic prevention and public health has become even more obvious than ever.However,the emergence of multiple severe acute respiratory syndrome coronavirus 2 variants worldwide has raised concerns about the effectiveness of current COVID-19 vaccines.Here,we review the characteristics of COVID-19 vaccine candidates in five platforms and the latest clinical trial results of them.In addition,we further discuss future directions for the research and development of the next generation of COVID-19 vaccines.We also summarize the serious adverse events reported recently after the large-scale vaccination with the current COVID-19 vaccines,including the thromboembolism caused by the AstraZeneca and Johnson&Johnson vaccines.

The COVID-19 Vaccine in Clinical Trials: Where Are We Now?

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to scale up around the world, costing severe health and economic losses. The development of an effective COVID-19 vaccine is of utmost importance. Most vaccine designs can be classified into three camps: protein based (inactivated vaccines, protein subunit, VLP and T-cell based vaccines), gene based (DNA or RNA vaccines, replicating or non-replicating viral/bacterial vectored vaccines), and a combination of both protein-based and gene-based (live-attenuated virus vaccines). Up to now, 237 candidate vaccines against SARS-CoV-2 are in development worldwide, of which 63 have been approved for clinical trials and 27 are evaluated in phase 3 clinical trials. Six candidate vaccines have been authorized for emergency use or conditional licensed, based on their efficacy data in phase 3 trials. This review summarizes the strengths and weaknesses of the candidate COVID-19 vaccines from various platforms, compares, and discusses their protective efficacy, safety, and immunogenicity according to the published clinical trials results.