Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine enables quick upgrade of antigen sequence to combat emerging new variants. In an observer-blinded, randomized, placebo-controlled phase 2 trial, immunologically naïve 300 adults and 150 older participants were enrolled and randomized (1:1:1) to receive two doses of 20 µg or 30 µg of a SARS-CoV-2 mRNA vaccine (SYS6006) or placebo. Adverse events (AEs) were recorded through 30 days after the second dose. Live virus neutralizing antibody (Nab), S1 protein-specific binding antibody (S1-IgG) and cellular immunity were tested. Results showed that robust wild-type Nab response was elicited with geometric mean titers of 91.3 and 84.9 in the adults, and 74.0 and 115.9 in the elders, 14 days following the second dose (Day 35) in the 20-µg and 30-µg groups, respectively. All seroconverted for wild-type Nab except two participants. Nab against Omicron BA.5 was mild. Robust wild-type S1-IgG response was induced with geometric mean concentrations of 2751.0 and 3142.2 BAU/mL in adults, and 2474.1 and 2993.5 BAU/mL in elders at Day 35 in the 20-µg and 30-µg groups, respectively. S1-IgG against Omicron BA.2 was induced. Cellular immunity was elicited, particularly in enzyme-linked immunospot assay. The most frequent AEs were injection-site pain and fever. Most reported AEs were grade 1 or grade 2. The AE incidences were similar following the first dose and second dose. No vaccination-associated serious AE was reported. In conclusion, two-dose vaccination with SYS6006 demonstrated good safety, tolerability and immunogenicity in immunologically naïve healthy participants aged 18 years or more.

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.

目的 评价中国仓鼠卵巢细胞乙型肝炎(乙肝)疫苗(Chinese hamster ovary cell derived hepatitis B vaccine,HepB-CHO)接种后18-20年免疫持久性和回忆反应.方法 2017年10-11月在河北省正定县整群抽取1997-1999年出生且接种3剂次HepB-CHO的受试者开展问卷调查,采用化学发光法检测血清乙肝表面抗原(Hepatitis B surface antigen,HBsAg)、表面抗体(Hepatitis B surface antibody,HBsAb)和核心抗体(Hepatitis B core antibody,HBcAb),分析乙肝病毒标志物阳性率和HBsAb几何平均浓度(Geometric mean concentration,GMC);随机选择HBsAb和其他标志物均阴性的受试者,随机分为两组分别加强接种1剂次HepB-CHO和酵母细胞乙肝疫苗(Yeast cell derived HepB,HepB-Y),检测接种后30d血清HBsAb,比较抗体阳转率和GMC.结果 在1 352例受试者中,3剂次 HepB-CHO 接种后 18-20 年 HBsAg、HBsAb 和 HBcAb 阳性率分别为 0.4％(6 例)、74.5％(1 007 例)和 1.3％(18例),HBsAb阳性者HBsAb GMC为191mIU/mL.本次调查中HBsAg阳性者在2005年、2009年和2013年调查中均为阳性;4次调查显示同一队列的受试者HepB-CHO初次免疫后6-20年HBsAg、HBcAb和HBsAb阳性率未呈显著上升或下降趋势(趋势检验:x2=3.58,P＞0.05;x2=3.42,P＞0.05;x2=4.54,P＞0.05).248例HBsAb阴性受试者加强1剂次HepB-CHO或HepB-Y后HBsAb总阳转率为93.1％(231例),阳转者GMC为369mIU/mL;其中HepB-CHO、HepB-Y加强免疫受试者HBsAb阳转率分别为97.7％、88.3％(x2=8.43,P＜0.05),阳转者GMC分别为578mIU/mL、226mIU/mL(t=7.16,P＜0.05).结论 HepB-CHO初次免疫后18-20年具有良好的免疫持久性和回忆反应,提示普通人群无必要加强免疫.

Objective:To evaluate the safety of domestically produced pneumococcal 15-valent conjugate vaccine (PCV15) in healthy adults, children and infants.Methods:From January to August 2020, a single-center, single-arm trial was conducted at Hebei Clinical Vaccine Research Center, and a total of 100 subjects aged 2 months (at least 6 weeks old) or older were enrolled. The subjects were divided into five age groups: ≥18 years group, 1-5 years group, 7-11 months group, 3 months group, and 2 months (at least 6 weeks old) group, with 20 subjects in each group. Subjects in the ≥18 years and 1-5 years age groups received a single dose of the experimental vaccine, and those in the 7-11 months age group received the vaccine according to a 2-dose schedule of 0, 2 months. Those in the 3 months and 2 months age groups received the vaccine according to a 3-dose schedule of 0, 1, 2 months and 0, 2, 4 months, respectively. Adverse reactions within 30 days after vaccination were observed by regular follow-up and active reporting.Results:After one dose of the vaccine, 14 cases and 10 cases of adverse reactions occurred in ≥18 years and 1-5 years age groups, respectively. After two doses, there were 11 cases showing vaccine-related mild adverse reactions in the 7-11 months age group. In the 2-3 months age group, 26 cases (65.00%, 26/40) of adverse reactions occurred, with the occurrence of 12 cases and 14 cases in the 3 months and 2 months age groups, respectively. Systemic reactions were the main manifestation, including fever (57.50%, 23/40) and gastrointestinal reaction (diarrhea 15.00%, 6/40). Adverse reactions were mainly mild to moderate, and most occurred within 7 days after vaccination and lasted for a short time.Conclusions:The domestically produced pneumococcal 15-valent conjugate vaccine has good safety and high acceptability in various age groups.

Background Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. Methods We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. Results During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. Conclusion The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.

Background: A booster dose of COVID-19 vaccine is required to prolong immune persistence and strengthen the protection against variants. Therefore, we assessed the safety and immunogenicity of homologous boosting with an inactivated vaccine (CoronaVac), as well as the cross-neutralising activity against the Omicron variant in children and adolescents aged 3-17 years.Methods: In the phase 2 clinical trial, in Hebei province, China, participants aged 3-17 years were initially assigned (2:2:1) to a 1.5 μg dose or 3.0 μg dose of CoronaVac or a placebo group. Following a protocol amendment on September 13, 2021, half of the participants (cohort 1) in vaccine group received a booster dose 10 months (window period 30 days) after dose 2, and the other half of the participants (cohort 2) received a booster dose 12 months (window period 30 days) after dose 2. Participants in placebo groups withdrew from the study since the emergency use of COVID-19 vaccine in children and adolescents. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity rate of neutralising antibody to the live prototype SARS-CoV-2 at baseline, 28 days, 3 months, 6 months, 10 months, 12 months after dose 2 and at 28 days after dose 3. The cross-neutralising immunity against the SARS-CoV-2 Omicron (B.1.1.529) variant was detected, and the primary safety endpoint was adverse reactions within 28 days after the third dose. The trial is ongoing and registered with ClinicalTrials.gov, NCT04551547.Findings: 171 participants in cohort 1 (89% of the 192 participants) received a third dose 10 months after dose 2. By 10 months after dose 2, the GMTs of neutralising antibody against the prototype SARS-CoV-2 strain was down to 12.7 (95% CI 10.4-15.5) and 20.8 (95% CI 16.5-26.1) in the 1.5 μg group and 3.0 μg group, respectively. A third dose of CoronaVac increased GMTs to 597.7 (452.4-789.6) in the 1.5 μg group and 681.0 (545.2-850.7) in the 3.0 μg group. Seropositivity rates against the prototype in both groups were 100% at 28 days after dose 3. The GMTs of cross-neutralising antibody against the Omicron variant was 23.6 (17.7-31.4) in the 1.5 μg group and 34.5 (27.2-43.7) in the 3.0 μg group on 28 days after dose 3. Seropositivity rates against the Omicron variant were 77.6% (1.5 μg group) and 90.6% (3.0 μg group). 175 participants in cohort 2 (91% of the 192 participants) received a third dose 12 months after the dose 2. By 12 months after dose 2, the GMTs of neutralising antibody against the prototype was down to 16.8 (13.3-21.3) and 21.7 (18.1-26.0) in the 1.5 μg group and 3.0 μg group, respectively. A third dose of CoronaVac increased GMTs to 462.4 (364.4-586.6) in the 1.5 μg group and 745.2 (577.0-962.3) in the 3.0 μg group. Seropositivity rates against the prototype in both groups were 100% at 28 days after dose 3. The GMTs of cross-neutralising antibody against the Omicron variant was 24.0 (18.0-32.2) in the 1.5 μg group, and 40.0 (30.7-52.3) in the 3.0 μg group at 28 days after dose 3. Seropositivity rates against the Omicron variant were 78.8% (1.5 μg group) and 91.5% (3.0 μg group). Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. The most commonly reported reactions were injection-site pain (14 [4.1%] participants) and fever (5 [1.5%] participants). Only one (0.3%) of 346 participants reported serious adverse events within 28 days after dose 3 were mild and moderate in both cohorts. The most commonly reported reactions were injection-site pain (14 [4.1%] participants) and fever (5 [1.5%] participants). Only one (0.3%) of 346 participants reported serious adverse events within 28 days after dose 3.Interpretation: A third dose CoronaVac in children and adolescents inoculated 10 months or 12 months after dose 2 induced a robust immune anamnestic response to the prototype SARS-CoV-2, which remarkably increased the neutralising antibody titres and had a cross-neutralising immunity against the Omicron variant. Boosting with CoronaVac is safe and might have considerable neutralising potency against the Omicron variant in children and adolescents.Clinical Trial Registration Details: NCT04551547Funding: The National Key Research and Development Program (2020YFC0849600) and BeijingScience and Technology Program (Z201100005420023).Declaration of Interest: QG, LiW and JL are employees of Sinovac Life Sciences Co., Ltd. YH, HZ, and LeW are employees of Sinovac Biotech Ltd. All other authors declare no competing interests.Ethical Approval: The amended protocols and informed consent form for the study were approved by Hebei CDC Ethics Committee (IRB2021-414, IRB2022-078).

Data on safety and immunity elicited by a third booster dose of inactivated COVID-19 vaccine in children and adolescents are scarce. Here we conducted a study based on a double-blind, randomised, placebo-controlled phase 2 clinical trial (NCT04551547) to assess the safety and immunogenicity of a third dose of CoronaVac. In this study, 384 participants in the vaccine group were assigned to two cohorts. One received the third dose at a 10-months interval (cohort 1) and the other one at a 12-months interval (cohort 2). The primary endpoint is safety and immunogenicity following a third dose of CoronaVac. The secondary endpoint is antibody persistence following the primary two-dose schedule. Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. A third dose of CoronaVac increased GMTs to 681.0 (95%CI: 545.2-850.7) in cohort 1 and 745.2 (95%CI: 577.0-962.3) in cohort 2. Seropositivity rates against the prototype were 100% on day 28 after dose 3. Seropositivity rates against the Omicron variant were 90.6% (cohort 1) and 91.5% (cohort 2). A homologous booster dose of CoronaVac is safe and induces a significant neutralising antibody levels increase in children and adolescents.

Background Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. Methods In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 mu g dose or 6 mu g dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1.5 mu g, 3 mu g, or 6 mu g of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS- CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per- protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 mu g groups, since 3 mu g is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. Findings 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 mu g group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3.9 [95% CI 3.1-5.0]) and for cohort 2b-28d-8m (n=49; 6.8 [5.2-8.8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137.9 (95% CI 99.9-190.4) for cohort 1b-14d-8m and 143.1 (110.8-184.7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21.8 (95% CI 17.3-27.6) on day 28 after the second dose to 45.8 (35.7-58.9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38.1 (28.4-51.1) to 49.7 (39.9-61.9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9.2 (95% CI 7.1-12.0) in cohort 1a-14d-2m and 10.0 (7.3-13.7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42.9 (95% CI 31.0-59.4) on day 28 after the second dose to 158.5 (96.6-259.2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. Interpretation A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. Copyright (C) 2021 Published by Elsevier Ltd. All rights reserved.

Background: The purpose of our study was to determine the persistence of CoronaVac vaccine-induced immunity from a primary three-dose regimen and a primary two-dose plus one booster dose given after an 8-month interval regimen in adults aged 18 years and older. Methods: In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were allocated (1:1:1:1) into four vaccination schedule cohorts: cohort 1a-14d-2m, cohort 1b-14d-8m, cohort 2a-28d-2m, and cohort 2b-28d-8m, with 14d and 28d representing the interval in days between the first two doses, and 2m and 8m denoting the actual median interval in months between the second and third doses. Each cohort was randomly assigned (2:2:1) to receive either a 3 μg dose or a 6 μg dose of CoronaVac or a placebo. In the other phase 2 trial, conducted in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1.5 μg, 3 μg, or 6 μg of vaccine or a placebo, administered 28 days apart for the first two doses and 8 months later for dose three. The primary outcomes of the study were geometric mean titres (GMTs) and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who received their assigned doses). Our reporting is focused on the 3 μg groups in cohort 2b-28d-8m and cohort 3-28d-8m, since 3 μg is the licensed formulation and an additional (third) dose is recommended at a 6-month interval after the second primary dose. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. Findings: In adults aged 18-59 years of age, 268 (89%) of 300 participants completed a 1-year follow up after their primary three-dose series (cohort 1a-14d-2m and cohort 2a-28d-2m), and 259 (86%) of a different 300 participants completed their 6-month follow up after receiving booster doses (cohort 1b-14d-8m and cohort 2b-28d-8m). In the 3 μg groups, neutralising antibody titres induced by booster doses declined approximately 4-fold after 6 months for cohort 1b-14d-8m (GMT from 137.9 [95%CI 99.9-190.4]) to 33.4 [95% CI 25.0-44.6]) and cohort 2b-28d-8m (GMT from 143.3 [95%CI 112.3-182.8]) to 36.4 [95% CI 28.7-46.1]). GMTs decreased 5-fold after 6 months and remained stable between 6 months and 1 year following a primary third dose, from 45·8 (95% CI 35.7-58.9) on day 28 to 9.2 (95%CI 7.1-12.0) on day 180 and 8.3 (95%CI 6.1-11.3) 1 year after the third dose in cohort 1a-14d-2m, and from 49.7 (95%CI 39.9-61.9) to 10.0 (95%CI 7.3-13.7) and to 10.7 (95%CI 7.6-15.1) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older, GMTs declined from 158.5 (95%CI 96.6-259.2) on day 28 to 53.2 (95%CI 39.7-71.1) on day 180 following the booster dose in the 3 μg group, a 2.5-fold decrease. There was one serious adverse event (1%) reported among the 259 participants in cohort 1b-14d-8m and cohort 2b-28d-8m, and fourteen (5%) among the 303 participants in cohort 3-28d-8m during the 6 months after booster dose administration. Interpretation: There were increases in the magnitude and duration of neutralization and improvement in the kinetics of the humoral response with homologous booster doses of CoronaVac given 8 months after a primary two-dose immunization series, which could prolong protection and contribute to building our wall of population immunity.Clinical Trial Registration Details: The two trials were registered with ClinicalTrials.gov, NCT04352608 and NCT04383574.Funding Information: The study was supported by grants from National Key Research and Development Program (2020YFC0849600), Beijing Science and Technology Program (Z201100005420023), and Key Program of the National Natural Science Foundation of China (82130093).Declaration of Interests: H.Y. has received research funding from Sanofi Pasteur, GlaxoSmithKline, Yichang HEC Changjiang Pharmaceutical Company, and Shanghai Roche Pharmaceutical Company. None of those research funding is related to development of COVID-19 vaccines. Q.X. and T.Y. were the employees of Sinovac Biotech Ltd., L.W. was the employee of Sinovac Life Sciences Co., Ltd. All other authors report no competing interests.Ethics Approval Statement: The complete study protocol for adults aged 18-59 years old was approved by the ethics committees of Jiangsu Provincial Centre for Disease Control and Prevention (JSJK2020-A021–02), and the complete study protocol for adults aged 60 years and older was approved by the ethics committees of Hebei Provincial Centre for Disease Control and Prevention (IRB2020–006). All participants gave written informed consent to participate in the study before administration of first doses and booster doses.

To evaluate the safety of the 15-valent pneumococcal conjugate vaccine (PCV15 (by LvZhu & Co. Ltd)) in healthy infants aged 2 months (minimum to 6 weeks) and 3 months old. This phase I clinical trial enrolled 80 subjects in Laishui County, Hebei Province, China. The total population was divided into 4 age groups on average: 20 adults (>= 18 years) and 20 children (1-5 years) all received one vaccine dose; 20 infants (3 months) received the vaccine according to a 3-dose schedule at 0, 1, and 2 months. Twenty infants (2 months, minimum of 6 weeks old) received the vaccine according to a 3-dose schedule of 0, 2, and 4 months. The adverse events (AEs) until 30 days after each dose and serious adverse events (SAEs) until 6 months after the whole dose were reported. The solicited and unsolicited AE frequencies and laboratory indices were similar among the treatment groups. No vaccine-related SAEs were reported. Most vaccine-related adverse events consisting of systemic and local reactions were fever and pain. One hypersensitivity manifested as systemic urticaria that occurred on the third day after the second dose in the 2-month group. The 15-valent pneumococcal conjugate vaccine was generally well tolerated in infants.

Objective:To understand the situation of hepatitis B booster vaccination in population and its influencing factors, so as to provide reference for hepatitis B booster immunization.Methods:The study was conducted in Zhengding county which was the monitoring site for observing the immune effect of hepatitis B vaccine and Dingxing county. Participants who were born from 1986 to 2011 and had completed hepatitis B primary vaccination were enrolled. A questionnaire survey was carried out among the participants to analyze the situation of hepatitis B booster immunization. Logistic regression analysis was used to identify the influencing factors.Results:A total of 3 447 participants were included, and the rate of hepatitis B booster vaccination was 32.93% (1 135 participants). Logistic regression analysis showed that the people at the age of 18-27 and 28-34, as well as high school (technical secondary school) education level had high incidence of booster vaccination[ OR(95% CI)=1.485(1.173-1.879), 1.855 (1.362-2.525) and 1.500 (1.234-1.825)]. People who had a history of marriage, lived in city, took examination for hepatitis B actively had high incidence of booster immunization[ OR(95% CI)=1.636(1.277-2.097), 1.390(1.077-1.794) and 1.201 (1.000-1.443)]. People living with family members without hepatitis B had low incidence of booster immunization[ OR(95% CI)=0.255(0.099-0.657)]. People who didn’t know whether they lived with HBV carriers had low incidence of booster immunization[ OR(95% CI)=0.186(0.062-0.552)]. The incidence of booster immunization in people with the score of hepatitis B knowledge ≥16 was lower than that of ≤11 [ OR (95% CI)=1.789 (1.371-2.333)], and in people with the score of risk attitude 9-11 was higher than that of 5-8[ OR(95% CI)=1.472(1.149-1.886)]. Population in monitoring site had a lower incidence rate than those in non-monitoring site[ OR(95% CI)=0.304(0.248-0.372)]. Conclusions:The occurrence of hepatitis B booster vaccination is related to multiple factors. Strengthening the propaganda of hepatitis B and hepatitis B vaccine related knowledge can promote the occurrence of hepatitis B booster vaccination.

A case-control study was conducted to evaluate the efficacy of continuous veno-venous hemofiltration (CVVH) combined with Xuebijing in the treatment of severe sepsis. In order to verify this claim, this study included 100 patients with severe sepsis treated in our hospital from February 2019 to April 2021. The patients were randomly divided into control group and study group. The control group was treated with CVVH, and the study group was treated with CVVH combined with Xuebijing. The curative effect and mortality, NT-proBNP, PCT, Ca∼_(2+), white blood cell count, neutrophil ratio, blood gas analysis, and APACHE-II score were compared between the two groups. The total effective rate of the study group was better than that of the control group (P < 0.05). The fatality rate in the study group was lower than that in the control group (P < 0.05). The levels of NT-proBNP and PCT in the study group were lower than those in the control group, while the level of serum calcium in the study group was higher than that in the control group. After treatment, the white blood cell count (WBC) and neutrophil count in the study group were (13.76 ± 1.28) × 109 shock L and (73.48 ± 1.23)%, respectively, which were significantly lower than those in the control group (17.45 ± 1.36) × 109 shock L and (77.82 ± 1.44)% (P < 0.05). After treatment, the levels of APTT, PT, and DD in the study group were lower than those in the control group. The level of FIB in the study group was significantly higher than that in the control group after treatment. After treatment, the PaO2 and PaO2/FiO2 of the study group were higher than those of the control group, and the APACHE-II score of the study group was lower than that of the control group. CVVH combined with Xuebijing is of positive significance in the treatment of severe sepsis and is worth popularizing.

ObjectiveTo evaluate the safety of an inactivated coronavirus disease 2019 (COVID-19) vaccine in healthy children and adolescents aged 3 – 17 years. MethodsTotally 500 healthy children and adolescents aged 3 – 17 years were recruited in Zanhuang county of Hebei province and randomly assigned into a vaccination group (n = 375) and a placebo group (n = 125) during May 2021. Two doses of inactivated COVID-19 vaccine (Sinovac Life Sciences Co., Ltd, Beijing) or placebo (day 0 and day 28) were administered to the participants. The participants were observed for adverse reactions within 30 minutes after each vaccination. The participants′ information on local and systemic solicited adverse events from day 0 to day 7, and unsolicited adverse events from day 0 to day 28 were collected after the vaccination. Serious adverse events were recorded from the beginning of vaccination to 6 months after the second dose vaccination to evaluate the safety of the vaccine.ResultsThe incidence of adverse reactions was 19.2% (72/375) in the vaccination group and 15.2% (19/125) in the placebo group, without significant difference between the incidence of the two groups (P > 0.05). The most common adverse reactions were injection site pain and fever. There was no significant statistical difference in the incidence of other adverse reactions between the two groups except for pain at the injection site. Most observed adverse reactions were grade 1 and 2 in severity, only 3 participants reported grade 3 adverse reactions. The vaccination group′s incidences of adverse reactions of grade 1 (14.93% vs. 12.8%), grade 2 (7.73% vs. 4%), and grade 3 (0.53% vs. 0.8%) were not significantly different from those of the placebo group. No serious vaccination-related adverse event was reported in either group. The incidence of adverse reactions was higher (28%) in the 3 – 5 years old participants than those in the participants aged 6 – 11 and 12 – 17 years (16% and 15.5%) and the age-group-specific adverse reaction incidences were not significantly different between vaccination group and placebo group. The incidence of adverse reactions for the first dose vaccination was significantly higher than that for the second dose (14.6% vs. 5.69%, P < 0.05) and there was no significant difference in the dose order-specific adverse reaction incidence between the vaccination group and the placebo group.ConclusionThe inactivated COVID-19 vaccine is of good safety when administered in 3 to 17 years old healthy children.

BackgroundTo determine the non-inferiority of the seven common serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) in the 13-valent pneumococcal conjugate vaccine (PCV13) with each serotype conjugated to a tetanus toxoid carrier protein and adsorbed on aluminum phosphate and the superiority of its six additional serotypes (1, 3, 5, 6A, 7F, and 19A) to the serotypes in the PCV7.MethodsParticipants were evenly randomized in a 1:1 ratio into either the PCV13 or PCV7 groups, to receive three doses of the vaccine at the age of 3, 4, and 5 months, respectively, and a booster dose between 12 and 15 months of age. Serotype-specific antibodies were measured using a standardized enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic activity (OPA) microcolony assay method.ResultsA total of 1,040 healthy infants were enrolled. All the seven common serotypes in the PCV13 were non-inferior to those in the PCV7 in terms of the serotype-specific IgG production induced; however, non-inferiority was not shown for serotype 6B after the infant series. The proportion of subjects who reached OPA antibody titers ≥ 1:8 in the PCV13 group was 89.25% or higher. Local reactions and systemic events were mild or moderate in severity and similar between the two groups. No new safety signals were observed.ConclusionThe newly developed PCV13 was immunogenic for all serotypes and had a comparable safety profile to the marketed PCV7.

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n = 3200) or placebo (n = 3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAES) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.

Objective:To investigate the sero-epidemiological features of HBV infection among people aged 1-29 years in Hebei province in 2014, so as to provide references for estimating the efficiency of measures on prevention and control of the disease.Methods:In 2014, a stratified two-stage cluster sampling method was used to select the subjects from local residents aged 1-29 years in 8 sites in Hebei province. A questionnaire survey was conducted to obtain basic information, including birth date, age, ethnicity, gender and so on. Blood samples were collected to detect HBV markers and statistical analysis was performed to compare the positive rates of HBsAg, anti-HBs and anti-HBc among different groups.Results:A total of 1 015 subjects aged 1-29 were involved in this survey in 2014. The positive rates of HBsAg, anti-HBs and anti-HBc were 1.08%, 53.50% and 6.60%, respectively. The positive rates of HBsAg, anti-HBs and anti-HBc had statistically significant differences among different age groups (1-4, 5-14 and 15-29 years old) ( χ2=14.43, 59.62 and 43.23, P all<0.01) . The positive rates of anti-HBs were 51.98%, 68.18% and 58.82% in Han, Manchu and other ethnic group, respectively, with statistically significant differences ( χ2=59.62, P<0.05) . For the people born during 2002-2013 when hepatitis B vaccine was integrated in expanded program of immunization (EPI) , the positive rates of HBs, anti-HBsAg and anti-HBc were 0.29%, 57.65% and 3.38%, respectively. And the positive rates of the three serum markers in different age groups were significantly different ( χ2trend=13.12, 14.43 and 52.58, P all<0.05) . There were 8 modes of HBV markers detected, in which single anti-HBs positive mode and negative mode of 5 indicators were the most common ones with the detection rates of 49.06% and 44.34%, respectively. Conclusions:The positive rate of HBsAg is low among people aged 1-29 years in Hebei province, and the HBsAg prevalence has decreased to less than 1% since HBV vaccine was integrated into EPI. It shows that the national EPI strategy for hepatitis B has achieved good effect.

BackgroundA vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older.MethodsWe did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 μg, 3 μg, or 6 μg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574).FindingsBetween May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8–100·0]) in the 3 μg group and 22 of 23 (95·7% [78·1–99·9]) in the 6 μg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 μg group (90·7% [83·1–95·7]), 96 of 98 in the 3 μg group (98·0% [92·8–99·8]), and 97 of 98 (99·0% [94·5–100·0]) in the 6 μg group. There were no detectable antibody responses in the placebo groups.InterpretationCoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 μg dose were similar to those of the 6 μg dose, and higher than those of the 1·5 μg dose, supporting the use of the 3 μg dose CoronaVac in phase 3 trials to assess protection against COVID-19.FundingChinese National Key Research and Development Program and Beijing Science and Technology Program.

Importance: Whether herd immunity through mass vaccination is sufficient to curb SARS-CoV-2 transmission requires an understanding of the duration of vaccine-induced immunity, and the necessity and timing of booster doses. Objective: To evaluate immune persistence of two priming doses of CoronaVac, and immunogenicity and safety of a third dose in healthy adults [≥]60 years. Design, setting, and participants: We conducted a vaccine booster study built on a single-center, randomized, double-blind phase 1/2 trial of the two-dose schedule of CoronaVac among healthy adults[≥]60 years in Hebei, China. We examined neutralizing antibody titres six months or more after the second dose in all participants. We provided a third dose to 303 participants recruited in phase 2 trial to assess their immune responses. Interventions: Two formulations (3 g, and 6 g) were used in phase 1 trial, and an additional formulation of 1.5 g was used in phase 2 trial. All participants were given two doses 28 days apart and followed up 6 months after the second dose. Participants in phase 2 received a third dose 8 months after the second dose. Main outcomes and measures: Geometric mean titres (GMT) of neutralizing antibodies to live SARS-CoV-2 and adverse events were assessed at multiple time points following vaccination. Results: Neutralizing antibody titres dropped below the seropositive cutoff of 8 at 6 months after the primary vaccination in all vaccine groups in the phase 1/2 trial. A third dose given 8 months or more after the second dose significantly increased neutralizing antibody levels. In the 3 g group (the licensed formulation), GMT increased to 305 [95%CI 215.3-432.0] on day 7 following the third dose, an approximately 7-fold increase compared with the GMT 28 days after the second dose. All solicited adverse reactions reported within 28 days after a booster dose were of grade 1 or 2 severity. Conclusion and relevance: Neutralizing antibody titres declined substantially six months after two doses of CoronaVac among older adults. A booster dose rapidly induces robust immune responses. This evidence could help policymakers determine the necessity and the timing of a booster dose for older adults. Trial registration: ClinicalTrials.gov (NCT04383574).

ABSTRACT Background Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity. Methods This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6–12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA). Results The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups. Conclusions The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.

In 1996, 3,515 susceptible children aged one to 12 years were recruited in a randomized, open trial to assess the efficacy of a live-attenuated HA vaccine. A comprehensive and systematic assessment of long-term persistence of anti-HAV antibodies, as well as protection against infection conferred by vaccine was performed based on this cohort. During the 17-year follow-up, the sero-positive rate and the geometric mean concentrations declined from 94.9% and 131.3 mIU/mL (91.5-188.4mIU/mL) at the peak to 55.6% and 41.1 mIU/mL (95% CI: 27.8-61.0 mIU/mL) respectively, with a similar natural infection rate in both groups. These results suggest that a booster dose is currently not necessary.