Post-marketing surveillance of adverse events following enterovirus type 71 inactivated vaccine in China, 2016-2023.

To assess adverse events following recombinant zoster vaccine (RZV) in China during the post-marketing period. The study obtained data on adverse events following immunization (AEFI) and vaccination doses of RZV from the Chinese National Immunization Information System (CNIIS). We analyzed RZV AEFI reports from 2020 through 2023. During the study period, 1.99 million doses of RZV were administered, and 10,525 RZV AEFI cases were reported. The reporting incidence of AEFI was 527.76 per 100,000 doses administered, with serious AEFI at 0.55, common vaccine reactions (usually minor) at 518.19, and rare vaccine reactions (possibly serious) at 4.06 per 100,000 doses. Among adverse vaccine reactions, the most frequently reported common vaccine reactions were fever (333.76/100,000) and local redness and swelling (213.51/100,000), while the main reported rare vaccine reaction was allergic rash (3.01/100,000). Most RZV AEFIs were common vaccine reactions, consistent with adverse events reported in RZV clinical trials. The incidence of rare vaccine reactions was very low, and most of which were allergic rash. No special safety concerns were identified and AEFI surveillance should be continued.

One dose of inactivated poliovirus vaccine (IPV) was introduced into the Chinese Expanded Program on Immunization (EPI) in 2016. IPV made from Sabin strains (sIPV) was newly licensed in China and its safety has been concerned. This study aimed to evaluate the safety of sIPV and provide a comparison with conventional IPV made from wild strains (wIPV). We collected all IPV-related AEFI reports in Jiangsu from the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) for 2016–2019. We obtained the administered doses of IPV from the Jiangsu provincial Electronic Immunization Registries System (JSEIRS). The AEFI reporting rates per 100,000 doses of vaccine administered were compared for sIPV and wIPV. A total of 699 sIPV and 908 wIPV AEFI cases were collected by CNAEFIS in Jiangsu during 2016–2019. The overall AEFI reporting rates were 53.02 per 100,000 doses and 41.25 per 100,000 doses for sIPV and wIPV, respectively (P < .001). For both sIPV and wIPV, the AEFIs were mainly classified as common adverse reactions. The reporting rate of common adverse reactions was higher for sIPV than for wIPV (P < .001). The most frequently reported symptoms/signs were fever, persistent crying, injection site erythema/swelling, rash, and injection site induration. Only 1.14% of sIPV-associated and 2.31% of wIPV-associated AEFI cases were diagnosed as serious. No difference in reporting rate was observed for serious AEFIs (P = .272). sIPV has a favorable safety profile, although it exhibits a slightly higher reporting rate of common adverse reactions than wIPV.

Surveillance of adverse events following vaccination in the French armed forces, 2011–2012

Immunization information systems (IISs) play a central role in coordinating distribution, administration, documentation, and monitoring of COVID-19 vaccination. In this commentary, the authors provide an introduction to IISs and discuss how clinicians can help maximize their utility in the COVID-19 pandemic.

：Objective To detect VP1and 2A genes of Enterovirus type 71 (EV71) isolated from clinical specimens of patientswith light or heavy symptoms and analyze the homogeneity and phylogenetic tree. MethodsFifty clinical specimens of children with hand-foot-and-mouth disease ( HFMD) were dealedwith, which were tested by RT-PCR assay with specific primer pairs for EV71. EV71 isolatesfrom patients with light or heavy clinical symptoms were tested by RT-PCR assay with twospecific primer pairs for VP1 and 2A genes of EV71 respectively. All of the PCR productswere sequenced and compared with that of previously isolated EV71 isolates available fromGenBank by homogeneity and phylogenetic tree analyses. Results The RT-PCR resultsindicated that 30 isolates were EV71, 13 of 30 isolates were from clinical specimens ofpatients with light symptoms of hand-foot and mouth, the other were from clinicalspecimens of patients with heavy symptoms of complications. VP1 genes and 2A genes of 10EV71 isolated strains including 5 light strains and 5 heavy strains were sequenced andcompared with that of previously isolated 5 EV71 Chinese isolates available from GenBank(fuyangEU703814.1, xi_anHM003207. 1, shandongEU753418.1, shenzhenFJ607337.1,henanGU366191. 1) by homogeneity and phylogenetic tree analyses. The homogeneity of VP1and 2A genes of the 10 EV71 isolated strains and 5 previously isolated strains werebetween 94.7% -99.4% and 93.6% -99.3% respectively, with the representative isolates of Aand B genotypes was between 81.0%-84. 6% and 78. 4%-82. 2% respectively. The datasuggested that all of the 10 Chinese isolates belong to EV71 genotype C. There were only87.8% -90.2% homology among these 10 strains and the representative strains of C1, C2, C3sub-genotypes of EV71 but 96. 8% -99.6% homology among these 10 strains and therepresentative strains of C4 sub-genotypes of EV71, this suggested that these 10 Chineseisolates composed the C4 sub-genotype, of the C genotype, that formed a single branch inthe phylogenetic tree. Conclusion EV71 of sub-genotype C4 distributed in Mainland China,and VP1 genes have close genetic relationship between isolated strains. There is noobvious difference in 2A genes between clinical specimens of patients with light or heavysymptoms by homogeneity and phylogenetic tree analyses.

This study investigated the incidence and characteristics of adverse events following immunization (AEFI) with the domestic bivalent human papilloma virus (HPV) vaccine among females aged 9–45 years in Hebei Province between 2022 and 2024. All vaccination and AEFI data were obtained from the Immunization Information Management System (IIMS) and the National Adverse Event Following Immunization Surveillance System (NAEFISS) in Hebei Province. Descriptive and analytical epidemiological methods were used for statistical analysis. The domestic bivalent HPV vaccine had an AEFI reporting rate of 4.54 per 100,000 doses, comprising common vaccine reactions (3.97/100,000), rare vaccine reactions (0.42/100,000). Significant differences in common vaccine reactions were observed across age groups 9–14 years versus both 15–26 years (χ2 = 6.222, p = .016) and 27–45 years (χ2 = 26.082, p < .001), whereas rare vaccine reactions showed no significant age-based differences (all p > .05). The AEFI reporting rates in 2022, 2023, and 2024 were 2.47, 4.70, and 9.93 per 100,000 doses, respectively, showing a significant linear increasing trend (r = 0.004, p < .05). The highest AEFI reporting rate occurred between April and June (5.50 per 100,000 doses). Statistically significant differences were observed between the 1st dose versus both the 2nd (χ2 = 6.618, p = .012) and 3rd doses (χ2 = 11.205, p = .001), but not between the 2nd and 3rd doses (χ2 = 1.466, p = .275). Among clinical symptoms, common vaccine reactions primarily included fever and injection-site swelling/induration, while allergic rash was the most frequent rare vaccine reaction. The 9–14-year-old age group exhibited a higher risk of AEFI compared to both the 15–26-year-old and 27–45-year-old groups, with the majority of events being common vaccine reactions.

Objective To observe the dynamics of neutralizing antibody titers at different time points after immunization with enterovirus type 71 (EV71) vaccine. Methods A randomized, open-label clinical trial was conducted. One hundred and twenty infants aged 6-35 months in Zhejiang province were recruited as subjects and were randomly divided into 3 groups. The serum was collected at 10 days, 20 days, and 30 days after 1 dose of EV71 vaccine in each group. EV71 neutralizing antibody was detected to study immunogenicity at different time points after initial immunization with EV71 vaccine. An open-label design was conducted to study 343 subjects in phase III clinical trials in Jiangsu province in 2012. Venous blood samples were collected to detect EV71 neutralizing antibodies 64 months after the first dose of vaccine was administered, so as to evaluate the antibody persistence over 5 years. Results The results of the Zhejiang study showed that the seropositive rate before inoculation was only 3.8%(4/104). Pre-immune antibody geometric mean titer (GMT) was 1:5.0. The seropositive rates of EV71 vaccine antibody at day 10, 20 and 30 after inoculation with 1 dose of EV71 reached 89.2% (33/37), 80.6% (25/31) and 66.7% (24/36), respectively and the GMTs were 1:24.6, 1:1:12.9, and 1:13.8, respectively. The seropositive rates (P<0.01) and GMT (Z10=-5.03, Z20=-3.73, Z30=-4.31, all P<0.01) at each time point were statistically higher than those before vaccination; The results of the Jiangsu study showed that the seropositive rates were 94.3% (100/106) and 71.4% (75/105) at 64-month in vaccine group and placebo group, respectively. The indicator was statistically higher in the vaccine group than that in the placebo group (x2=19.567, P<0.01). The GMT was 1:141.4 and 1:71.8, respectively and the indicator was statistically higher in the vaccine group than in the placebo group (t=2.60, P=0.01). Conclusions EV71 vaccine can stimulate immune response quickly after vaccination and showed good persistence over five years. Key words: Hand, foot, and mouth disease; Enterovirus infections; Viral vaccines; Immunocompetence

The Haemophilus influenzae type b (Hib) conjugate vaccine is widely administered in China. We extracted data on Hib vaccine doses administered and adverse events following immunization (AEFI) reported between 2010 and 2021 from the Chinese National Immunization Information System (CNIIS). A descriptive analysis was conducted to examine the characteristics and incidence rates of AEFI with the Hib vaccine. In China, between 2010 and 2021, a total of 52,910 AEFIs with the Hib vaccine were reported, resulting in an overall AEFI reporting rate of 38.10 per 100,000 doses. Common (typically minor) and rare (potentially serious) vaccine reactions occurred at rates of 34.71 and 2.78 per 100,000 doses, respectively. Among the common vaccine reactions, the incidences of fever (axillary temperature ≥38.6 ℃), injection site redness and swelling (>2.5 cm in diameter), and injection site induration (>2.5 cm in diameter) were 11.93, 9.69, and 3.38 per 100,000 doses, respectively. Rare vaccine reactions included anaphylactic rash, angioedema, and febrile convulsion with reported incidences of 2.42, 0.10, and 0.05 per 100,000 doses, respectively. The incidence of serious rare vaccine reactions was 0.16 per 100,000 doses. The reported incidence of AEFI with the Hib vaccine was low, with the occurrence of serious rare adverse reactions also being markedly low throughout the period 2010-2021 in China.

Objective: To analyze vaccination situation of oral live attenuated rotavirus vaccine (LLR strain) among children from six provinces in China. Methods: In 2014, we selected 12 counties in Guangdong, Jiangsu, Chongqing, Jiangxi, Heilongjiang and Gansu provinces by using stratified cluster random sampling method and extract information of children born from January 1, 2008 to December 31, 2012 from Children's Immunization Information System. We investigated ten children of each birth cohort in each county by checking the vaccination certification, and a total of 606 children were investigated. A survey was conducted to check the information of the children's vaccination certification with the data of Children's Immunization Information System by questionnaire including the basic information (province, county, name, gender, birth date, etc) and the rotavirus vaccination (vaccination date, dose, etc) to analyze the rotavirus vaccination situation. Results: 340 of 606 children were male. There were 121, 124, 122, 119 and 120 children born in 2008-2012, respectively. The proportions of the first and the second dose of rotavirus vaccination were 32.8% (199) and 9.7% (59). The proportion of the third dose of rotavirus vaccination among children born between 2008 and 2010 was 3.5% (13) since children born in 2011 and 2012 did not reach the age of third dose vaccination. The proportion of the first dose of rotavirus vaccination in high, middle and low per capita disposable income areas was 45.0% (91), 37.7% (77) and 15.5% (31) respectively (χ(2)= 43.15, P<0.001). Among 199 children vaccinated with the first dose of vaccine, the vaccination age mainly concentrated in 2 to 21 months, of which the peak was 5 to 13 months (66.8%, 133). The intervals between 2 doses of vaccination were mainly from 12 to 13 months (42.4%, 25) among the 59 children who received at least 2 doses of vaccine. In the 13 children vaccinated with 3 doses, the intervals between the second and the third dose were 12 months (5). Of the 271 doses of rotavirus vaccine vaccinated during 2008-2014, 34.7% (94 doses) were vaccinated in June-August, 88 were vaccinated simultaneously with 18 other vaccines, accounting for 32.5% of the total. Of the 18 other vaccines, inactivated vaccines such as diphtheria vaccine (30 doses), Hib vaccine (14 doses), group A meningitis vaccine (10 doses) were predominant. Conclusion: The proportion of rotavirus vaccination was low and the vaccination age was relatively late. The vaccination mode was different from the recommendation of WHO. It is recommended that routine immunization of rotavirus vaccines should be carried out in early-months of children.

BackgroundA medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health.DescriptionThe Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA.ConclusionOAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e.g., vaccinee age) important for determining their clinical outcomes.

BackgroundLicensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO).ResultsLike OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term ‘human vaccinee population’ is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed.ConclusionsThe ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents enables the identification of adverse events from vaccination in relation to predefined parts of the population (age groups) and certain groups of vaccines. The resulting ontology-based VAE knowledge base classifies vaccine-specific VAEs and supports better VAE understanding and future rational AE prevention and treatment.

The propagation of rumours about rare but severe adverse vaccination or infection events through social networks can strongly impact vaccination uptake. Here we model a coupled behaviour-disease system where individual risk perception regarding vaccines and infection are shaped by their personal experiences and the experiences of others. Information about vaccines and infection either propagates through the network or becomes available through globally available sources. Dynamics are studied on a range of network types. Individuals choose to vaccinate according to their personal perception of risk and information about infection prevalence. We study events ranging from common and mild, to severe and rare. We find that vaccine and infection adverse events have asymmetric impacts. Vaccine (but not infection) adverse events may significantly prolong the tail of an outbreak. Similarly, introducing a small risk of a vaccine adverse event may cause a steep decline in vaccine coverage, especially on scale-free networks. Global dissemination of information about infection prevalence boosts vaccine coverage more than local dissemination. Taken together, these findings highlight the dangers associated with vaccine rumour propagation through scale-free networks such as those exhibited by online social media, as well as the benefits of disseminating public health information through mass media.

Using Electronic Medical Records to Enhance Detection and Reporting of Vaccine Adverse Events

Domestic Sabin-strain inactivated poliovirus vaccine (sIPV) was approved for use in China in 2015 and introduced into the national immunization schedule in a sequential schedule with oral poliovirus vaccine (OPV) in May 2016. However, a comprehensive analysis describing the characteristics, occurrences, and incidences of adverse events following immunization (AEFI) with sIPV in China is lacking. Data on sIPV doses administered and AEFI reported from 2015 to 2022 were obtained from the Chinese National Immunization Information System (CNIIS). Descriptive epidemiological methods and statistics were used to analyze and describe the characteristics, occurrences, and incidences of AEFI following sIPV in China from 2015 to 2022. From 2015 to 2022, over 110,000,000 sIPV doses were administered, and 46,748 sIPV AEFIs were reported, resulting in an AEFI reporting rate of 42.44/100,000. Most AEFIs (46,333, 99.11%) were non-serious. Causality assessment determined 46,061 (98.53%) AEFIs were vaccine product-related reactions, including 44,001 (94.12%) common and 2,060 (4.41%) rare vaccine reactions. Among common vaccine reactions, reporting rates for fever >38.5 °C, local redness and swelling ≥2.6 cm, and local induration ≥2.6 cm were 12.02/100,000, 5.13/100,000, and 1.67/100,000, respectively. Among rare vaccine reactions, reporting rates for anaphylactic rash, thrombocytopenic purpura, and febrile convulsion were 1.56/100,000, 0.09/100,000, and 0.03/100,000, respectively. Most reported sIPV AEFIs were non-serious, and the reporting rate of rare vaccine reactions has been very low since sIPV was approved for use in China. As sIPV remains in use in China, surveillance of AEFIs associated with this vaccine needs to be maintained.

To evaluate the safety of enterovirus type 71 (EV71) inactivated vaccine (human diploid derived) for infection prevention in an animal model by investigating the immune responses and related patho-inflammatory reactions. In the neonatal monkey model for EV71 vaccine protection, vaccinated group (n = 4) and unvaccinated group (n = 4) were attacked with live virus at the same time, the parameters of clinical observations, antibodies and inflammatory factors in peripheral blood and cerebrospinal fluid (CSF) were detected. And the pathological changes in major organs were used to determine the patho-inflammatory reactions during the immune responses elicited by vaccination. The neutralizing antibodies of vaccine group reach to 1:32. There was no obvious changes of inflammatory factors in peripheral blood and CSF of monkeys challenged or unchallenged by live virus. In peripheral blood of unvaccinated group, the level of basophilic granulocyte higher 4 - 5 times than normal level and the interferon-γ (IFN-γ) showed obvious increase. Live virus infected after 7 days, the interleukin-6 (IL-6) and IFN-γ in peripheral blood of unvaccinated group (18.5, 12.7 pg/ml) were higher than vaccinated group (10.2, 7.6 pg/ml). Furthermore, the IL-6 in CSF (102.0 pg/ml) had 4 - 5 times increased than vaccinated group (12.4 pg/ml) at 7 days after virus exposure. Meanwhile, the pathological analysis revealed that no obvious changes were detected in CNS and other organs of vaccinated monkeys challenged with live virus. However, the pathological damages induced by virus infection could be determined in the unvaccinated control monkeys, including neuronal damage, massive cellular infiltration associated with pulmonary edema/hemorrhage and pulmonary/bronchial damage due to an infiltration of inflammatory cells. Capable of inducing an immune response, the EV71 inactivated vaccine offers protection to neonatal rhesus monkeys against the attacks of live virus. Based on the results of no patho-inflammatory reaction and pathological damage after viral infection in vaccinated animals, the excellent safety of this vaccine may be confirmed in neonatal monkey.