A review of potential use cases for measles-rubella, measles-mumps-rubella, and typhoid-conjugate vaccines presented on microarray patches.

As an innovative vaccine delivery technology, vaccine microarray patches could have a meaningful impact on routine immunization coverage in low- and middle-income countries, and vaccine deployment during epidemics and pandemics. This review of the potential use cases for a subset of vaccine microarray patches in various stages of clinical development, including measles-rubella, measles-mumps-rubella, and typhoid conjugate, highlights the breadth of their applicability to support immunization service delivery and their potential scope of utilization within national immunization programs. Definition and assessment of the use cases for this novel vaccine presentation provide important insights for vaccine developers and policymakers into the strengths of the public health and commercial value propositions, and the preparatory requirements for public health systems for the future rollout of vaccine microarray patches. An in-depth understanding of use cases for vaccine microarray patches serves as a foundational input to overcoming the remaining technical, regulatory, and financial challenges. Additional efforts will help to realize the potential of vaccine microarray patches as part of the global effort to improve the coverage and equity of national immunization programs.

[Epidemiological characteristics of mumps among people aged 0-14 in Jiangxi Province, 2015-2022].

Objective: To analyze the epidemic characteristics of mumps in people aged 0-14 years in Jiangxi Province and the vaccination situation of mumps-containing vaccines (including mumps vaccines) from 2015 to 2022 to provide a scientific basis for the prevention and control of mumps epidemic in Jiangxi Province. Methods: The mumps epidemic situation and mumps vaccination data in Jiangxi Province from 2015 to 2022 were obtained from Chinese Disease Prevention and Control Information System and Jiangxi Immunization Program Information System and were analyzed using descriptive epidemiological methods. The chi-square test, cluster analysis, and Cochran-Armitage trend test were used for statistical analysis. Results: From 2015 to 2022, a total of 40 734 cases of mumps were reported in people aged 0-14 in Jiangxi Province, with an annual average reported incidence rate of 53.69/100 000, and the peak of incidence occurred in aged 6-7 years group, and the reported incidence rate was 86.43/100 000. The high incidence seasons in 2015-2019 were summer and winter, and there was no significant high incidence season in 2020-2022. Mumps outbreaks mainly occurred in Shangrao, Ganzhou, and Ji'an, and the outbreak sites were mainly reported primary schools. From 2015 to 2019, the 1-year group was the primary age group for vaccination against mumps, while from 2020 to 2021, it was 0 and 1-year groups. Conclusions: From 2015 to 2022, the incidence of mumps in the population aged 0-14 in Jiangxi Province showed a downward trend, and the peak of incidence occurred in age group 6-7 years. It is suggested to continue to strengthen the coverage rate of 2 doses of mumps vaccination for school-age children and, simultaneously, strengthen the monitoring and prevention of mumps in key places to avoid outbreaks.

[Experience with the use of pharmacopoeial reference material for the activity of measles vaccine].

INTRODUCTION: Due to the increased incidence of measles in Russia and in many other regions of the world, vaccines for the measles prevention are especially in demand. Ensuring the quality of the measles vaccine for effective disease prevention is within the scope of the tasks of the state policy of our country. OBJECTIVE: Evaluation of the experience of using a pharmacopoeial standard material of measles vaccine activity for measurement of the specific activity of the measles virus in vaccines with a measles component that are used in the Russian Federation for measles prevention. MATERIALS AND METHODS: The object of the study was the Pharmacopoeia reference material (PRM) of the activity of the live measles vaccine of series 10. The activity of PRM was analyzed when determining the specific activity of the measles, mumps-measles and combined vaccines for the prevention of measles, rubella and mumps, as well as based on the materials of the summary protocols for the production of these vaccines. RESULTS: The titer of the measles virus in the PRM for each determination of the specific activity of the measles virus in vaccines in the Scientific Centre for Expert Evaluation of Medicinal Products in 2021-2022, as well as according to the summary production protocols, was within the boundaries of the certified value (4.63 ± 0.5) lgTCD50/0.5 ml, and the test results met the acceptance criteria in accordance with the requirements of regulatory documentation. During the observation period, the average value of the PRM titer (4.61 lgTCD50/0.5 ml) practically did not differ compared to the average value of the certified characteristics of the PRM, the standard deviation of the mean value of the measles virus titer in the PRM did not exceed 0.15 lgTCD50, which indicated the stability of the analytical work at the enterprise and in IC. CONCLUSION: The data obtained indicate the stable activity of PRM, the correctness of the determination of the measles virus titer in the vaccination dose of the vaccine, and the validity of the method for monitoring the specific activity of the measles virus in vaccines.

Genome-wide determinants of cellular immune responses to mumps vaccine.

BACKGROUND: We have previously described genetic polymorphisms in candidate genes that are associated with inter-individual variations in antibody responses to mumps vaccination. To expand upon our previous work, we performed a genome-wide association study (GWAS) to discover host genetic variants associated with mumps vaccine-induced cellular immune responses. METHODS: We performed a GWAS of mumps-specific immune response outcomes (11 secreted cytokines/chemokines) in a cohort of 1,406 subjects. RESULTS: Among the 11 cytokine/chemokines we studied, four (IFN-γ, IL-2, IL-1ß, and TNFα) demonstrated GWAS signals reaching genome-wide significance (p < 5 × 10-8). A genomic region (encoding Sialic acid-binding immunoglobulin-type lectins/SIGLEC) located on chromosome 19q13 (p < 5 × 10-8) was associated with both IL-1ß and TNFα responses. The SIGLEC5/SIGLEC14 region contained 11 statistically significant single nucleotide polymorphisms (SNPs), including the intronic SIGLEC5 rs872629 (p = 1.3E-11) and rs1106476 (p = 1.32E-11) whose alternate alleles were significantly associated with decreased levels of mumps-specific IL-1ß (rs872629, p = 1.77E-09; rs1106476, p = 1.78E-09) and TNFα (rs872629, p = 1.3E-11; rs1106476, p = 1.32E-11) production. CONCLUSIONS: Our results suggest that SNPs in the SIGLEC5/SIGLEC14 genes play a role in cellular and inflammatory immune responses to mumps vaccination. These findings motivate further research into the functional roles of SIGLEC genes in the regulation of mumps vaccine-induced immunity.

Safety analysis of a live attenuated mumps vaccine in healthy adolescents in China: A phase 4, observational, open-label trial.

Mumps is an acute infectious disease, which was well controlled in the past, but recently it has resurged in some areas. This study aimed to evaluate the safety profile of the live attenuated mumps vaccine after large-scale vaccination. We conducted an observational, open-label phase 4 trial in Shaanxi, China from October 2020 to March 2021. Eligible participants were freshmen of junior high school who were not above 14 years old. Adverse events following immunization (AEFI) monitoring was carried out by active and passive surveillance. Safety follow-ups were conducted during the study participation. Overall, 10057 subjects were enrolled in the active surveillance analysis. A total of 214 subjects reported adverse reactions with an incidence of 2.13% (214/10057). Most adverse reactions were grade 1, and the incidence of grade 1 adverse reactions was 1.44% (145/10057); 0.60% for grade 2 (60/10057); and 0.09% for grade 3 (9/10057). The majority of adverse reactions were solicited (1.73%, 174/10057). Injection-site pain was the most frequently reported local adverse reaction (0.71%, 71/10057), followed by redness (0.29%, 29/10057). The most common systemic adverse reactions were nausea (0.19%, 19/10057) and fever (0.16%, 16/10057). For passive AEFI surveillance, 57 AEFI cases were reported, with an incidence of 19.28/100000 (57/287608). And most AEFI cases were common adverse reactions (66.67%, 38/57). In total, the live attenuated mumps vaccine evaluated in this trial has a favorable safety profile and can be used for large-scale inoculation.

Mumps vaccine hesitancy: Current evidence and an evidence-based campaign in Japan.

BACKGROUND: Mumps is still endemic in Japan because mumps vaccination is voluntary. In this study, we investigated associations of parental socioeconomic status, family structure, and knowledge/belief about mumps and mumps vaccine with parental decision to vaccinate their children. We also evaluated effectiveness of a campaign based on survey results. METHODS: We conducted a cross-sectional survey of parents with children aged 1-6 years attending preschools or kindergartens in Tokamachi City, Japan. We assessed the association of parental factors with their decision to vaccinate their children using multivariable logistic regression analyses. We designed a campaign based on the survey results, and compared the number of annual vaccinations at Tokamachi Hospital per the child population aged 1-6 years in Tokamachi City before and after the campaign using a trend test. RESULTS: In total, 1391 of 1617 (86%) eligible parents completed the survey. Among these parents, 229 (16%) vaccinated their children. In multivariable analyses, higher parental education [odds ratio (OR) = 2.21; 95% CI, 1.59-3.08; P < 0.001], greater knowledge about mumps and the mumps vaccine (OR = 1.88; 95% CI, 1.60-2.21; P < 0.001), and living without grandparents (OR = 1.44; 95% CI, 1.05-1.99; P = 0.024) were significantly associated with parental decision to vaccinate their children. The number of annual vaccinations per the child population significantly increased following the campaign (P < 0.001). CONCLUSION: Our study showed several sociodemographic factors significantly associated with mumps vaccination. Further research is needed to examine the relevance of our findings to the uptake of other voluntary vaccines among children.

Changes in vaccination administration in Japan.

This paper reviews the administration related to vaccination in Japan after the enactment of the Immunization Act in 1948, under which vaccination was implemented mandatory for the public. To enhance the effectiveness of vaccination activities, the government implemented group vaccination, which is convenient for vaccinating recipients all at once. In 1976, Japan established the relief system for health damage after vaccination. While some projects, such as the mass administration of live oral polio vaccine in 1961, achieved excellent results, incidents leading to health damage occurred, such as the diphtheria toxoid immunization incident (1948) and frequent occurrence of aseptic meningitis owing to the measles, mumps, and rubella vaccine (1989). In December 1992, the Tokyo High Court sentenced that the onset of health damage after vaccination could be attributed to the negligence of the national government. In the revision of the Immunization Act in 1994, the "mandatory vaccination" enforced until then was changed to "recommended vaccination." The Act was also changed to recommend "individual vaccination" in principle, which is performed after primary care physicians investigate the physical condition of individual recipients and carefully conduct preliminary examination. For approximately 20 years from the 1990s, a vaccine gap existed between Japan and other countries. From around 2010, efforts have been made to bridge this gap and establish the global standard in vaccination.

Impact of the COVID-19 lockdown on routine childhood vaccination coverage rates in Catalonia (Spain): a public health register-based study.

OBJECTIVE: The aim of this study was to determine the impact of the lockdown measures adopted during the COVID-19 pandemic on routine childhood vaccination coverage rates in Catalonia (Spain) and to estimate its recovery once the progressive return to 'normalcy' had begun. STUDY DESIGN: We conducted a public health register-based study. METHODS: Routine childhood vaccination coverage rates were analysed in three periods: a first pre-lockdown period (from January 2019 to February 2020), a second lockdown period with full restrictions (from March 2020 to June 2020), and, finally, a third post-lockdown period with partial restrictions (from July 2020 to December 2021). RESULTS: During the lockdown period, most of the coverage rates remained stable, concerning the pre-lockdown period; however, when comparing the vaccination coverage rates in the post-lockdown period to the pre-lockdown period, we observed decreases in all types of vaccines and doses analysed, except for coverage with the PCV13 vaccine in 2-year-olds, which experienced an increase. The most relevant reductions were observed in measles-mumps-rubella and diphtheria-tetanus-acellular pertussis vaccination coverage rates. CONCLUSIONS: Since the beginning of the COVID-19 pandemic, there has been an overall decline in routine childhood vaccine coverage rates, and the pre-pandemic rates have not yet been recovered. Immediate and long-term support strategies must be maintained and strengthened to restore and sustain routine childhood vaccination.

Mumps-specific antibody persistence in children aged 3-7 years immunized with two doses of mumps-containing vaccines: A prospective cohort study in Jiangsu Province, China.

Mumps reemergence has been reported in developed countries with high levels of two-dose mumps-containing vaccine (MuCV) coverage. The effectiveness of the two-dose MuCV may be compromised by limitations in the persistence of immunity. This prospective cohort study evaluated the persistence of immunity of a two-dose MuCV in children aged 3-7 years from 2015 to 2020. Persistence of antibody to mumps, determined as the geometric mean antibody concentration (GMC), and seropositivity were analyzed for both repeated measurements from three follow-ups and on each cross-section, respectively. A total of 105 eligible subjects were recruited. Their overall seropositivity rate was relatively high and stable (92.4%-84.8%), while the overall GMC decreased from 547.6 U/ml to 333.3 U/ml. Analysis of waning immunity in 91 participants showed a significant and consistent downward trend for GMC, which differed significantly in boys and girls. The overall seropositivity rate decreased slightly from 2015 (95.6%) to 2016 (92.3%) but both were significantly higher than in 2018 (84.6%). The rates in girls remained stable, while those in boys declined to 75% in 2018. The seropositivity rate of the cross-section level decreased from 95.4% to 86.4% in 4 years. Although two-dose MuCV may result in a high level of immunity, antibody concentrations decay over 2 years after the second dose. Children with waning immunity after receiving two doses, especially boys, require further surveillance at 4 years and later to avoid future mumps epidemics.Clinical trial registration: NCT02901990.

[Quality analysis of a combined domestic vaccine for the prevention of measles, rubella and mumps].

INTRODUCTION: The need to maintain a high level of vaccination coverage against measles, rubella and mumps in conditions of an increased risk of outbreaks of infections due to violations of vaccination tactics associated with the pandemic of coronavirus infection and due to the unfavorable epidemic situation in neighboring countries determines the advisability of using a combined vaccine for the simultaneous prevention of these three socially significant infections. THE AIM OF THE STUDY: to analyze the quality of commercial series of a new domestic combined cultured live vaccine against measles, rubella and mumps (MRM) throughout the entire time of its manufacturing according to all specification indicators in regulatory documentation (RD). MATERIALS AND METHODS: The object of the study was the combined cultured live vaccine against measles, rubella and mumps. The analysis of the quality of the drug was carried out according to 86 consolidated production protocols of manufactured series, as well as according to the results of control of these series in the Testing Center for Quality Expertise of the Federal State Budgetary Institution NCESMP of the Ministry of Health of the Russian Federation. RESULTS: It is shown that the quality of the combined drug for the prevention of measles, rubella and mumps corresponds to the RD in all studied indicators. The drug does not contain an antibiotic. Bovine serum albumin, which is a technological impurity, is detected in quantities more than 5 times lower than the established norm. A comparison of the specific activity of the viral components of new combined domestic vaccine and the components of the bivalent vaccine against measles and mumps produced by the company in 20192021 showed that the spread of the activity values of the viral components in the new drug and in the series of mumps-measles vaccine was minimal, which allowed us to make a conclusion about the stability of the production technology. CONCLUSION: The quality of the new domestic combined vaccine for the prevention of measles, rubella and mumps meets WHO requirements. The results of the conducted studies indicate the stability of production and the standard quality of the drug. The use of a combined vaccine against three significant infections will ensure the necessary level of vaccination coverage in the population. Information about the results of studies can help reduce the number of vaccination refusal.

Mumps-specific IgG, IgG subclasses and neutralization titres to the vaccine and outbreak mumps strains differ in vaccinated healthy controls, breakthrough mumps infection cases and naturally infected individuals.

BACKGROUND: Despite widespread use of the mumps vaccine resulting in significant reduction in the incidence of symptomatic mumps infection, large outbreaks continue to occur in highly vaccinated populations. OBJECTIVES: We examined the mumps-specific IgG, IgG subclasses and neutralization titres to the outbreak Genotype G5 and Jeryl Lynn vaccine (Genotype A) mumps strains. STUDY DESIGN: Sera from 207 individuals were classified into five distinct cohorts: healthy controls and mumps cases of 5-17 years and 18-25 years, and naturally infected individuals of 50+ years. Mumps specific IgG and IgG subclass levels were measured using modified ELISA assays with lysates and nucleoprotein antigens from both the mumps vaccine and circulating Genotype G5 strains. All sera were investigated for in vitro neutralizing antibody titres (GMT) using focus reduction neutralization assays. Data was analysed using the Kruskal-Wallis test and pairwise Wilcoxon tests. RESULTS: Mumps cases had higher mumps IgG levels compared to controls, to both the vaccine and outbreak strains, however levels decreased with age. Mumps IgG3 levels were significantly raised in mumps cases (p < 0.001). Neutralization titres were lower to the outbreak strain in all cohorts with titres markedly lower in the mumps cohorts compared to healthy controls. Mean GMT to the vaccine strain increased with age. The naturally infected group displayed the highest GMT to the JL vaccine and the lowest GMT to the outbreak strain. CONCLUSIONS: Antigenic differences between mumps vaccine strain and circulating mumps viruses decrease the cross-neutralization capacity of vaccine-induced antibodies which may play a role in breakthrough infection.

Establishment of a model to assess mumps virus neurovirulence in neonatal Wistar rats.

Mumps virus (MuV) is highly neurotropic and neurovirulent, hence, the neurovirulence of virus seeds used in the production of mumps vaccines must be tested. The previous neurovirulence evaluation method involves measuring the area of the cavity in the Lewis neonatal rat brain caused by MuV through paraffin sectioning and hematoxylin-eosin (HE) staining. However, the processes of paraffin sectioning and HE staining are time consuming and complicated. To solve this problem, in this study, a vibratome sectioning system was first deployed to evaluate MuV neurovirulence in the rat brain instead of paraffin sectioning and HE staining. The results showed that the vibratome sectioning method could assess the neurovirulence potential of MuV more objectively and efficiently. In addition, the effects of different MuV doses and the ages of the rats in days on this evaluation method were explored. The results indicate that MuV at no less than 10 50 % cell culture infective dose (CCID50) could cause obvious cavity formation in 1-day-old rat brains. The neonatal rat model developed in this study could evaluate the neurovirulence of different MuV strains with high sensitivity and good repeatability.

Refractory status epilepticus with fever due to mumps vaccine-induced encephalitis caused secondary encephalopathy mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Encephalitis due to vaccination for mumps is a rare complication that occurs in 0.00004% of recipients, and there has been no report of serious neurological sequelae. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported as the most frequent type among acute encephalopathy syndromes in the pediatric population in Japan. There has been no report of AESD caused by vaccinations. Case presentation We present the clinical course of a 1-year and 10-month-old boy who had no preexisting condition, and developed mumps vaccine-induced severe primary encephalitis. Refractory status epilepticus due to encephalitis persisted for 16 h and resulted in secondary encephalopathy as a form of AESD mimic. He had serious neurological sequelae, such as West syndrome, transient spastic tetraplegia, and intellectual disability, despite intensive treatments. DISCUSSION: The presented boy is the first patient to develop mumps vaccine-induced primary encephalitis with severe central nervous system (CNS) damage. Screening of the immunological background in the presented patient revealed no abnormalities; therefore, it is unclear why he developed such severe adverse events. In patients with acute encephalitis caused by the herpes simplex virus 1, inborn immune errors in CNS based on mutations in single genes are involved in its pathophysiology. Consequently, some immunogenetic alterations could be found by further analysis in the presented patient.

Assessment of mumps-containing vaccine effectiveness by dose during 2006 to 2020 in Quzhou, China.

Mumps cases were reported frequently when a routine dose measles-mumps-rubella(MMR) achieved high coverage in Quzhou. The supplementary immunization activities (SIA) using measles mumps (MM) was conducted to control mumps outbreaks. The effectiveness of one and two doses of mumps-containing vaccine (MuCV) was assessed using surveillance data in this study. Mumps cases and immunization information were retrieved from the National Notifiable Disease Reporting System (NNDRS) and the Zhejiang Provincial Immunization Information System (ZJIIS), respectively. Mumps cases of children born from 2006 to 2010 were included. Vaccine effectiveness by dose was calculated using the screening method. A total of 956 mumps cases were identified, of whom 754 (78.9%) had received one dose of MuCV; 108 (11.3%) had received two doses; 94 (9.8%) were unvaccinated. The coverage of one-dose MuCV in the 2006-2010 birth cohorts ranged from 91.6% to 98.9%. Except the 2009 birth cohort in which the coverage of two doses of MuCV was 55.1%, the others were less than 10%. Vaccine effectiveness (VE) of one dose ranged from 47.4% to 86.0%, while VE of two doses ranged from 64.0% to 92.4%. The VE of one and two doses of MuCV waned over time, but the VE of two doses was consistently higher than that of one dose in the same period. The vaccine schedule with two-dose MMR should be implemented among children in Quzhou. The optimal age for the second dose needs to be further evaluated.

[Genetic diversity of the mumps viruses (Paramyxoviridae: Orthorubulavirus: Mumps orthorubulavirus): an overview].

Mumps is an infectious disease controlled by specific vaccine prophylaxis. To date, its social and epidemiological significance remains high. This is evidenced by the process of developing and implementing into the health care practices of many countries a set of measures for surveillance of mumps. In the Russian Federation, the National Program «Elimination of measles and rubella and achievement of sporadic morbidity with epidemic mumps in the Russian Federation (2021-2025)¼ and the national plan for its implementation were adopted in 2021. The basis for the adoption of these documents was the development of the domestic trivalent vaccine for the prevention of measles, rubella and mumps, Vaktrivir, and the start of its clinical application. The availability of this vaccine will make the epidemiological surveillance of mumps to be a part of the existing system of appropriate measures for measles and rubella. The fulfillment of this set of tasks involves the study of the molecular epidemiology of the mumps virus (MuV) with possible subsequent implementation of its methodology into the surveillance actions. In this connection, this work was aimed at presenting the data on global genetic diversity of MuV as well as its genotyping methods in a systematized form. The analysis of MuV global genetic diversity in different years will be the starting point in the subsequent development of approach to monitoring virus strains circulating in the Russian Federation.

Immunogenicity of Mumps Virus Genotype G Vaccine Candidates in Jeryl Lynn-Immunized Mice.

Mumps virus (MuV) causes a highly contagious human disease characterized by the enlargement of the parotid glands. In severe cases, mumps can lead to neurological complications such as aseptic meningitis and encephalitis. Vaccination with the attenuated Jeryl Lynn (JL) MuV vaccine has dramatically reduced the incidence of MuV infection. Recently, large outbreaks have occurred in vaccinated populations. The vaccine strain JL was generated from genotype A, while most current circulating strains belong to genotype G. In this study, we examined the immunogenicity and longevity of genotype G-based vaccines. We found that our recombinant genotype G-based vaccines provide robust neutralizing titers toward genotype G for up to 1 year in mice. In addition, we demonstrated that a third dose of a genotype G-based vaccine following two doses of JL immunization significantly increases neutralizing titers toward the genotype G strain. Our data suggest that after two doses of JL vaccination, which most people have received, a third dose of a genotype G-based vaccine can generate immunity against a genotype G strain. IMPORTANCE At present, most individuals have received two doses of the measles, mumps, and rubella (MMR) vaccine, which contains genotype A mumps vaccine. One hurdle in developing a new mumps vaccine against circulating genotype G virus is whether the new genotype G vaccine can generate immunity in humans that are immunized against genotype A virus. This work demonstrates that a novel genotype G-based vaccine can be effective in animals which received two doses of genotype A-based vaccine, suggesting that the lead genotype G vaccine may induce anti-G immunity in humans who have received two doses of the current vaccine, providing support for testing this vaccine in humans.

Vaccination-associated immune thrombocytopenia possibly due to ChAdOx1 nCoV-19 (Covishield) coronavirus vaccine.

Immune thrombocytopenia (ITP) is an acquired haemorrhagic diathesis of immune-mediated destruction, impaired production or increased splenic sequestration of platelets. It can be idiopathic (primary) or secondary (infections, medications, HIV infection, malignancies, connective tissue diseases or rarely secondary to vaccination). ITP postvaccination is termed vaccine-associated ITP (VITP) and is known to be caused by vaccines against various infectious agents such as measles-mumps-rubella, Haemophilus influenzae, pneumococcus, hepatitis B virus and human papilloma virus. Cases of VITP post SARS-CoV-2 vaccination have also been reported in the literature. Various hypotheses on the occurrence of the same are theorised, but no single theory has been proven to cause VITP conclusively. Management includes routine treatment of ITP with use of agents such as steroids, intravenous immunoglobulins, or on rare occasions a thrombopoietic agent or vinca alkaloids. We present a case of VITP possibly due to ChAdOx1 nCoV-19 (Covishield) vaccination in a middle-aged woman who responded to steroid therapy.

Annual trends in adverse events following mumps vaccination in Japan: A retrospective study.

BACKGROUND: In Japan, a monovalent mumps vaccine is provided on a voluntary basis. Due to public concerns over post-vaccination aseptic meningitis, the vaccination coverage is not high enough. The present study investigated the incidence of adverse events, including aseptic meningitis, after Torii strain-derived mumps vaccination. METHODS: This retrospective, observational study used data collected by a vaccine manufacturer regarding adverse events following mumps vaccinations at medical institutions between 1992 and 2018. In addition, the number of Torii strain-derived mumps vaccines shipped each year was obtained. The incidence (per 100,000 doses) and 95% confidence intervals (CIs) were calculated for all adverse events and each adverse event, categorized as aseptic meningitis, encephalitis, mumps, mumps complications, and others. RESULTS: During the study period, 8,262,121 mumps vaccine doses were shipped, and 688 subjects reported adverse events. The incidence for all adverse events (per 100,000 doses) was 8.33, and the incidence was 4.19 for aseptic meningitis, 0.33 for encephalitis, 0.80 for mumps, 0.25 for mumps complications, and 3.78 for others. The incidence of aseptic meningitis (per 100,000 doses) was 7.90 (95% CI: 5.61-10.18) between 1998 and 2000 but declined by half, to 3.91 (2.46-5.36), between 2001 and 2003. The most recent incidence (per 100,000 doses) of aseptic meningitis, for the period 2016 to 2018, was 2.78 (1.94-3.62). CONCLUSION: The incidence of post-vaccination aseptic meningitis has declined significantly since 2001, and the incidence has remained stable at fewer than 3 cases per 100,000 doses since 2010. Multiple factors might have contributed to the decline in aseptic meningitis incidence, including (i) lowered misclassification of aseptic meningitis resulting from echovirus infection; (ii) changes in the vaccine manufacturing process in 2000; and (iii) publication in 2008 of the recommendation for vaccination of children at 1 year of age.