[Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years].

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

[Willingness of receiving influenza vaccine and its influencing factors among health care workers in Yangtze River Delta region from 2020 to 2021].

Objective: To analyze the willingness of receiving influenza vaccine and its influencing factors among health care workers (HCWs) in Yangtze River Delta region from 2020 to 2021. Methods: Convenient sampling method was adopted. From July 2020 to March 2021, 76 hospitals in Jiangsu, Zhejiang, Anhui and Shanghai provinces were selected according to the hospital level and job position, and a questionnaire survey was conducted on the willingness of receiving influenza vaccination. Logistic regression model was used to analyze the influencing factors of vaccination intention. Results: A total of 1 332 HCWs were investigated, with a ratio of male to female about 1∶3.2, and the length of working years was (15.07±9.75) years. A total of 614 HCWs had received influenza vaccine in 2019, with a vaccination rate of 46.09%. About 63.21% (842/1 332) of HCWs were willing to be vaccinated with influenza vaccine. The results of binary logistic regression analysis showed that the willingness of receiving influenza vaccine among HCWs in primary hospitals was higher than that in secondary hospitals (OR=0.573) and tertiary hospitals (OR=0.357). The willingness of HCWs who had received influenza vaccine in 2019 was higher than that of HCWs who had not received influenza vaccine (OR=0.226) and had unknown history of influenza vaccination (OR=0.228). The willingness of HCWs in departments of prevention, health care and infection was higher than that in departments of pre-examination, outpatient, emergency, pediatrics and respiratory (OR=1.670). Conclusion: The willingness of receiving influenza vaccination among HCWs in Yangtze River Delta region is high, but it is still lower than that in developed countries. It is necessary to strengthen publicity and education to improve the influenza immunization level of HCWs.

[The surveillance analysis of the adverse events following immunization of the domestic 13-valent pneumococcal polysaccharide conjugate vaccine in Zhejiang Province].

To evaluate the safety of the domestic 13-valent pneumococcal polysaccharide conjugate vaccine-tetanus toxoid protein (PCV13-TT) after its licensure. The adverse event following immunization (AEFI) and the vaccination data of PCV13-TT in Zhejiang province from July 2020 to October 2021 were collected from national adverse event following immunization surveillance system and Zhejiang provincial immunization information system. Descriptive epidemiological method was used for this analysis. From July 2020 to October 2021, 302 317 doses of PCV13-TT were administered in children under 6 years old in Zhejiang Province and 636 AEFI case reports were received, with a reporting rate of 21.04 per 10 000 doses. Of these AEFI cases, 97.17% were mild vaccine product-related reaction (20.54 per 10 000 doses) and 95.44% occurred in the 0-1 d after vaccination (20.08 per 10 000 doses). The most common clinical diagnoses of AEFI included fever (224 cases), redness (204 cases), and induration (190 cases), while allergic rash (11 cases) was the most common diagnosis among the abnormal reactions. In conclusion,the present results bolstered that the domestic PCV13-TT was generally well tolerated in children under 6 years old in Zhejiang Province.

[Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines].

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

[Evaluating the real-world vaccine effectiveness using a regression discontinuity design].

Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.

[The prevalence rate and influencing factors of cough in children under 5 years old in Yiwu city, Zhejiang Province in 2019].

Objectives: To investigate the prevalence of cough and its influencing factors in community children under 5 years old. Methods: From October to December 2019, we selected 3 102 community children under the age of 5 from 50 natural villages/residential communities in 14 towns/streets of Yiwu, Zhejiang Province, using multi-stage random sampling method. A face-to-face and on-site questionnaire survey was conducted among child caregivers to collect demographic data and information about children's cough in the last 1 month. Multiple logistic regression model was used to analyze children's cough and the influencing factors of different cough states. Results: Multivariate logistic regression model analysis results showed that compared with 0-1 year old, dispersed, caregivers with education level below high school, families with 1 child under 5 years old, Cough risk was higher in 1-2, 2-3, 3-4 years old, nurseries, caregivers with education level of high school or above, and families with more than 2 children under 5 years old. OR (95%CI) values were 1.52(1.19-1.92), 1.65(1.29-2.10), 1.86(1.36-2.54), 2.59(1.99-3.38), 1.48(1.26-1.74) and 1.35(1.13-1.62), respectively. Further analysis of the influencing factors of different states of cough, multivariate logistic regression model analysis results showed that preschool status, the number of children under 5 years old in the family and the education level of caregivers were the influencing factors of acute, prolonged and chronic cough. Age was only an influencing factor of acute and persistent cough. Conclusions: The disease burden of cough in children under 5 years old community was heavy, and the cough was related to children's age, education level of caregivers, number of children under 5 years old in the family and childcare status.

[Safety and immunogenicity analysis of recombinant （hansenula polymorpha) hepatitis B vaccine （CpG ODN adjuvant) among adults: the preliminary results of phase I clinical trial].

Objective: To evaluate the safety and immune effect of recombinant hepatitis B vaccine （CpG ODN adjuvant). Methods: On Oct. 26, 2016, we launched volunteer recruitment in Kaihua county, Quzhou city, Zhejiang Province. In the randomized, double-blind, controlled trial, a total of 48 subjects with negative HBV screening tests and normal hepatorenal function among 18 and 60 years old were selected and divided into two groups randomly, 24 cases each. The experimental group was given 250 µg of CpG ODN recombinant （Hansenula polymorpha) Hepatitis B vaccine and the control group was given 10 µg of commercial Hepatitis B vaccine with timed at 0, 1and 6 months. The inoculation reactions were compared the difference between the two groups after observed and recorded in time periods. We also collected serum before and after immunization to compare the two groups of anti-HBs positive rate, geometric mean concentration（GMC). Results: During the study period, the incidence of adverse events was 66.67%（16/24) in the experimental group and 54.17%（13/24) in the control group, with no significant difference（P=0.556). The severities of adverse events were level 1 or level 2, and no level 3 or above adverse reactions occurred. After full-course immunization, in the FAS data set, the anti-HBs GMC in the experimental group [2 598.56（1 127.90-5 986.90) mIU/ml] was higher than that in the control group[371.97（164.54-840.91) mIU/ml] In the PPS set, the GMC of test group was 7 808.21（3 377.00-18 052.00) mIU/ml, which was higher than that of the control group [843.22（213.80-3 325.90) mIU/ml]. The anti-HBs positive rate of FAS（PPS) was 95.83%（100.00%) in the experimental group and the control group; The anti-HBs strongly positive rate of FAS（PPS) was 79.17%（90.00%) in the experimental group and 33.33%（50.00%) in the control group, with statistically significant differences among the FAS set（P=0.003) and no statistically significance differences among the PPS set（P=0.074). Conclusion: CpG Hepatitis B Vaccine is safe and shows better immunogenicity than the control vaccine.

[Disease burden of influenza in schools and child care settings in rural areas of Hangzhou, 2016-2018].

Objective: The objective of this study was to analyze the disease burden of influenza in schools and child care settings in rural areas of Hangzhou. Methods: Hospital visit influenza cases aged 3-17 years in hospitals that reported based on influenza surveillance system from 2016 to 2018 in Chun'an county, Hangzhou city were selected as study subjects and a total of 294 confirmed cases of influenza were selected using system sampling method. Questionnaires were designed to investigate the basic information and data on inpatients and outpatients among, health care and life quality, etc.. Direct and indirect economic burden and disability adjusted life year (DALY) were analyzed and compared among different age groups. Results: The mean age of investigated subjects was (8.88±3.92) years. A total of 143 (48.64%) investigated cases were male. In total of 283 (96.26%) cases were outpatients. The total economic burden was 124 743.95 CNY. The mean economic burden was 424.30 CNY per person. The mean direct and indirect economic burden was 361.33 and 62.97 CNY per person respectively. The difference of the mean direct, indirect and total economic burden per person between different age group was statistically significant (P<0.001). The 3-5 years age group showed the highest economic burden with the median value of direct, indirect and total economic burden per person being 276.24, 50.98 and 321.26 CNY, respectively, while the 12-17 years age group showed the lowest values with 175.30, 26.54, 201.79 CNY, respectively. The DALY of 294 influenza cases was 1.18, and the median of burden strength was 3.21 DALY/thousand. The difference of the burden of strength between different age group influenza case was statistically significant (P<0.001), of which the 12-17 years age group showed the highest value with 4.25 DALYs/thousand while the 3-5 years age group showed the lowest value with 2.60 DALY/thousand. Conclusion: The disease burden of influenza was heavy in schools and kindergartens in rural areas of Hangzhou city, with the cases aged from 3 to 5 years showing higher economic burden and cases aged from 12 to 17 years showing greater burden strength.

[Post-marketing multi-center safety surveillance of inactivated enterovirus A71 vaccine (Vero cell)].

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion: The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.

[Post-marketing safety analysis of inactivated enterovirus A71 vaccines].

Objectives: To evaluate the safety of inactivated enterovirus A71(EV-A71) vaccines after large-scale immunization in the community. Methods: We selected EV-A71 susceptible people (healthy children) aged 6-59 months in vaccination clinics from 89 counties in Zhejiang Province between April 2016 and March 2018. All local and systematic adverse actions were collected by 30 min on-site inspection, within 3 days and 4-30 days follow-up. Chi-square test and Fisher's exact test were used to compare the difference of AEs incidence in various characteristics among two groups. Results: A total of 71 663 doses of vaccines were included for active safety analysis, which included 37 331 doses in boys and 34 332 doses in girls. Among all the doses, children aged 6 to 11 months, 12 to 23 months and 24 to 59 months were received 13 707, 32 639 and 25 317 doses respectively. The incidence of adverse reactions within 30 min, 3 days and 4-30 days were 0.33% (239 doses), 1.58% (1 133 doses) and 0.34% (244 doses) respectively. Adverse reactions within 3 days were 1 372 doses, with a incidence of 1.91%; among all the cases, 539 doses (0.75%) were grade 1, 677 doses (0.94%) were grade 2 and 156 doses (0.22%) were grade 3, no grade-4 adverse reaction was reported. The common local adverse reactions were redness, swelling and pruritus, with the incidence rates were 0.05% (39 doses), 0.02% (16 doses) and 0.02% (12 doses), respectively, while the most common systemic adverse reaction was pyrexia with an incidence of 1.19% (856 doses), followed by diarrhea and anorexia with the incidence rates were 0.15% (104 doses) and 0.13% (90 doses) respectively. Conclusion: Most adverse actions of EV-A71 vaccines were mild and moderate and majority of them were common adverse actions. No new adverse reactions were found in the study.