Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.
Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines ; Pandemics/prevention & control* ; SARS-CoV-2 ; Viral Vaccines/adverse effects*

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.
Aged ; Aged, 80 and over ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Critical Illness ; Immunity ; Retrospective Studies ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects* ; Viral Vaccines/adverse effects*

OBJECTIVEUsing the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine.

METHODSObserving the safety and immune effects of different groups.

RESULTSData on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05).

CONCLUSIONResults showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.

Antibodies, Viral ; blood ; Child, Preschool ; Encephalitis Virus, Japanese ; immunology ; Humans ; Immunization ; Japanese Encephalitis Vaccines ; administration & dosage ; adverse effects ; immunology ; Vaccines, Attenuated ; immunology ; Vaccines, Inactivated ; immunology

OBJECTIVE: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. METHODS: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. RESULTS: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. CONCLUSION The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Data Collection ; Humans ; Rabies/prevention & control* ; Rabies Vaccines/adverse effects* ; Rabies virus/genetics*

OBJECTIVETo study the safety and immunogenicity of the measles-mumps-rubella combined vaccine (MMR) produced by Beijing Biological Product Institute.

METHODSChildren aged 10-12 years, 2-2.5 years and 8-12 months were selected to be vaccinated with Beijing MMR vaccine (test vaccine). Other groups of children with similar nature were vaccinated with measles vaccine, mumps vaccine and rubella vaccine while using imported MMR vaccine (control vaccine) as controls.

RESULTSThe safety of the Beijing MMR vaccine was confirmed after vaccinating 32 children above 2 years old. Among 104 children of 8-12 months were vaccinated with Beijing MMR vaccine, only 6.7% of the children had transient fever and 1.9% had signs of rashes but with no other signs observed. The positive seroconversion rates of measles, rubella and mumps anti-HI were 100%, 100% and 85.7% respectively. GMT also showed high lever.

CONCLUSIONThe MMR vaccine (Beijing) had good safety and immunogenicity which might be used to be the bases enhance immunization of measles.

Antibodies, Viral ; blood ; Child ; Child, Preschool ; Freeze Drying ; Hemagglutination Inhibition Tests ; Humans ; Measles-Mumps-Rubella Vaccine ; adverse effects ; immunology ; Vaccines, Attenuated ; adverse effects ; immunology

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

BACKGROUND: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. METHODS: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. RESULTS: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). CONCLUSIONS: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. TRIAL REGISTRATION UMIN000030786 .
Asthma ; epidemiology ; etiology ; Cohort Studies ; Dermatitis, Atopic ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; epidemiology ; etiology ; Humans ; Hypersensitivity ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Japan ; Male ; Vaccines, Inactivated ; adverse effects ; Viral Vaccines ; adverse effects

OBJECTIVETo compare the reactogenicity and serology between influenza subunit vaccine and split vaccine.

METHODSA randomized, double-blind study was carried out among children (age 6 - 12 years) in order to compare the safety and immunogenicity of an influenza inactivated subunit vaccine (Agrippal, Chiron Vaccines) with that of a split vaccine (Flurix, GSK).

RESULTSA total of 499 subjects were vaccinated and included in the safety analysis. A total of 249 subjects received Agrippal and 250 received Flurix. All subjects were kept under medical observation for 30 minutes in order to check the evidence of having any immediate local and systemic reaction. Daily observation records were collected during the 3-day follow-up after vaccination. 6.4% of the cases with fever >or= 37.5 degrees C was reported in the Flurix group, but 2.4% in Agrippal group which was significantly less than the former group (P > 0.05). Blood samples (the D0 pre- and D23 post-vaccination sera) were collected from 224 of Agrippal group and 223 of Flurix group and analysed by the haemagglutination inhibition (HI) assay. Agrippal and Flurix induced similar seroprotection (HI titer >or= 1:40, H1N1 99.6% vs 100.0%; H3N2 99.1% vs 99.1%) and seroconversion (4-fold increase, 95.1% vs 97.8%; H3N2 74.5% vs 79.8%) rates and geometric mean titer (GMT) increase (16.0 vs 21.0; 5.4 vs 6.4) against the two A subtypes. A similar seroprotection rate (94.2% vs 96.4%) and GMT increase (21.2 vs 18.2) against the influenza B strain were also noticed in both vaccines. No significant difference was found in the results of immunological assay between the two vaccines (P < 0.05). A lower seroconversion rate against B strain was observed in Agrippal group than in Flurix group (91.1% vs 97.3%).

CONCLUSIONIn terms of safety, both vaccines were generally well tolerated. The fever reaction was less frequently seen in the Agrippal group. Both vaccines induced an effective immune response in the vaccines.

Antibodies, Viral ; blood ; Child ; Double-Blind Method ; Female ; Fever ; chemically induced ; Hemagglutination Inhibition Tests ; Humans ; Influenza A virus ; immunology ; Influenza B virus ; immunology ; Influenza Vaccines ; adverse effects ; classification ; immunology ; Influenza, Human ; prevention & control ; Male ; Safety ; Vaccination ; Vaccines, Inactivated ; adverse effects ; immunology ; Vaccines, Subunit ; adverse effects ; immunology

We report a case of toxic epidermal necrolysis with ocular involvement following vaccination for hemorrhagic fever with renal syndrome. A healthy 20-year-old male soldier presented with confluent purpuric and erythematous dusky red macules evolving to flaccid blister and epidermal detachment on the whole body with conjunctival injection. The patient had no antecedent medical or surgical conditions except for two doses of hemorrhagic fever with renal syndrome vaccination. With supportive care, skin lesions were improved. Ophthalmic examinations revealed conjunctival injection with epithelial defects in both eyes. Ocular complications were resolved after amniotic membrane transplantation. Toxic epidermal necrolysis may be considered as a possible complication of hemorrhagic fever with renal syndrome vaccination.
Conjunctival Diseases/*etiology ; Epidermal Necrolysis, Toxic/*etiology ; Hemorrhagic Fever with Renal Syndrome/*prevention & control ; Humans ; Male ; Severity of Illness Index ; Viral Vaccines/*adverse effects ; Young Adult

To investigate the phenotypic characteristics of the strain of the rabies virus CTNCEC25, the strain of the China rabies virus CTN-1 adapted to primary chicken embryo cells (CECs), Vero cells, and mouse neuroblastoma N2a cells was inoculated with CTNCEC25 and parental CTN-1 strains to explore the cytopathic effect (CPE) and growth kinetics of CTNCEC25 on cultured cells. To determine the pathogenicity of CTNCEC25, suckling mice, adult mice, guinea pigs and rabbits were inoculated with CTNCEC25 via the intracerebral route and their survival monitored every day. Furthermore, the CTNCEC25 strain was passed serially in CECs for 20 passages and then 3 passages in the brains of suckling mice to determine phenotypic stability. CTNCEC25 achieved similar growth kinetics in Vero cells and N2a cells compared with parental CTN-1, but CTNCEC25 replicated more efficiently in CECs than the CTN-1 strain with a titer 72 h after infection reaching 10(7.5-7.6) FFU/mL, which was significantly higher than the 10(5.8) FFU/mL achieved by its parental strain, CTN-1. Moreover, CTNCEC25 induced apparent CPE in Vero cells, CECs and N2a cells. Analyses of intracerebral inoculation demonstrated that CTNCEC25 was attenuated profoundly in adult mice and was completely apathogenic to guinea pigs and rabbits, though it caused death in suckling mice. The CTNCEC25 strain proliferated steadily after serial passage in CECs and the brains of suckling mice, and remained avirulent in adult mice. These results suggest that CTNCEC25 is a highly attenuated and genetically stable strain of the rabies virus. CTNCEC25 replicated stably and efficiently in cultured cells and achieved high titers, so it could be a promising and safe vaccine strain for rabies prevention in China.
Animals ; Cell Line ; Cercopithecus aethiops ; China ; Guinea Pigs ; Humans ; Mice ; Rabbits ; Rabies ; virology ; Rabies virus ; genetics ; growth & development ; pathogenicity ; Serial Passage ; Viral Vaccines ; adverse effects ; genetics ; Virulence