Shedding of measles vaccine RNA in children after receiving measles, mumps and rubella vaccination.

BACKGROUND: Measles, mumps, and rubella(MMR) vaccination is critical to measles outbreak responses. However, vaccine reactions and detection of measles vaccine RNA in recently immunized persons may complicate case classification especially in those presenting with another respiratory viral illness. We aim to characterize cases of measles vaccine shedding in recently vaccinated children presenting with respiratory viral symptoms. METHODS: Children who were tested with a multiplex respiratory panel <30 days after receiving MMR were identified. Remnant nasopharyngeal(NP) samples were tested for measles vaccine by PCR. Medical records were reviewed for demographics, presenting symptoms, and test results. RESULTS: From January 2022 to March 2023, 127 NP from children who received MMR were tested. Ninety-six NP were collected after the first dose, of which 33(34.4 %) were positive for vaccine RNA. The median interval between MMR and detection was 11.0 days. Thirty-one NP were collected after the second MMR and 1(3.2 %) was positive; time between the vaccination and detection was 18.9 days. Median cycle threshold(Ct) value of the measles PCR for vaccine shedding was significantly higher than median Ct in children with wild-type infection. CONCLUSION: Shedding of measles vaccine RNA is not uncommon and vaccine RNA can be detected up to 29 days post MMR; the amount of vaccine RNA shedding is low indicated by high Ct values. Clinicians and public health officials should consider performing measles vaccine testing on those testing positive for measles within one month of MMR vaccination, especially if the Ct value is high and definitive epidemiological links are absent.

Immunity against measles, mumps, rubella, and varicella among homeless individuals in Germany - A nationwide multi-center cross-sectional study.

Introduction: Homeless individuals suffer a high burden of vaccine-preventable infectious diseases. Moreover, they are particularly susceptible to adverse infection outcomes with limited access to the health care system. Data on the seroprevalence of measles, mumps, rubella, and varicella within this cohort are missing. Methods: The seroprevalence of measles, mumps, rubella, and varicella was determined within the homeless population in Germany. Predictors of lacking immune protection were determined using multivariable logistic regression analysis. Results: Homeless individuals in Germany (n = 611) showed a seroprevalence of 88.5% (95% CI: 85.8-91.0) for measles, 83.8% (95% CI: 80.6-86.6) for mumps, 86.1% (95% CI: 83.1-88.7) for rubella, and 95.7% (95% CI 93.8-97.2) for varicella. Measles seroprevalences declined from individuals born in 1965 to individuals born in 1993, with seroprevalences not compatible with a 95% threshold in individuals born after 1980. For mumps, seroprevalences declined from individuals born in 1950 to individuals born in 1984. Here, seroprevalences were not compatible with a 92% threshold for individuals born after 1975. Seronegativity for measles, mumps and rubella was associated with age but not with gender or country of origin. Discussion: Herd immunity for measles and mumps is not achieved in this homeless cohort, while there was sufficient immune protection for rubella and varicella. Declining immune protection rates in younger individuals warrant immunization campaigns also targeting marginalized groups such as homeless individuals. Given that herd immunity thresholds are not reached for individuals born after 1980 for measles, and after 1975 for mumps, vaccination campaigns should prioritize individuals within these age groups.

Evaluation of the Interactions between Mumps Virus and Guinea Pig.

Mumps is a highly contagious viral disease that can be prevented by vaccination. In the last decade, we have encountered repeated outbreaks of mumps in highly vaccinated populations, which call into question the effectiveness of available vaccines. Animal models are crucial for understanding virus-host interactions, and viruses such as mumps virus (MuV), whose only natural host is the human, pose a particular challenge. In our study, we examined the interaction between MuV and the guinea pig. Our results present the first evidence that guinea pigs of the Hartley strain can be infected in vivo after intranasal and intratesticular inoculation. We observed a significant viral replication in infected tissues up to 5 days following infection and induction of cellular and humoral immune responses as well as histopathological changes in infected lungs and testicles, without clinical signs of disease. Transmission of the infection through direct contact between animals was not possible. Our results demonstrate that guinea pigs and guinea pig primary cell cultures represent a promising model for immunological and pathogenetic studies of the complex MuV infection. IMPORTANCE Understanding of mumps virus (MuV) pathogenesis and the immune responses against MuV infection is limited. One of the reasons is the lack of relevant animal models. This study explores the interaction between MuV and the guinea pig. We demonstrated that all tested guinea pig tissue homogenates and primary cell cultures are highly susceptible to MuV infection and that α2,3-sialylated glycans (MuV cellular receptors) are being abundantly expressed at their surface. The virus remains in the guinea pig lungs and trachea for up to 4 days following intranasal infection. Although asymptomatic, MuV infection strongly activates both humoral and cellular immune response in infected animals and provides protection against virus challenge. Infection of the lungs and testicles after intranasal and intratesticular inoculation, respectively, is also supported by histopathological changes in these organs. Our findings give perspective for application of guinea pigs in research on MuV pathogenesis, antiviral response, and vaccine development and testing.

A case of autoimmune encephalitis with involuntary movements as the first symptom and suspected association with mumps virus infection.

This case involved a 72-year-old woman. From the day after mitral annuloplasty, a fever over 37°C and ballismus-like involuntary movements of the right upper and lower limbs appeared. A few month later, involuntary movements spread throughout the body, and she developed impairment of consciousness and difficulty speaking and eating. Levels of protein in cerebrospinal fluid were high. Positive results were seen for serum mumps immunoglobulin G and M antibody. Because steroid pulse therapy proved effective, we suspected autoimmune encephalitis associated with mumps virus infection.

Response to Vaccination against Mumps in Medical Students: Two Doses Are Needed.

Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p < 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p < 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.

Novel mumps virus epitopes reveal robust cytotoxic T cell responses after natural infection but not after vaccination.

Mumps is nowadays re-emerging despite vaccination. The contribution of T cell immunity to protection against mumps has not been clearly defined. Previously, we described a set of 41 peptides that were eluted from human leukocyte antigen (HLA) class I molecules of mumps virus (MuV)-infected cells. Here, we confirmed immunogenicity of five novel HLA-B*07:02- and HLA-A*01:01-restricted MuV T cell epitopes from this set of peptides. High frequencies of T cells against these five MuV epitopes could be detected ex vivo in all tested mumps patients. Moreover, these epitope-specific T cells derived from mumps patients displayed strong cytotoxic activity. In contrast, only marginal T cell responses against these novel MuV epitopes could be detected in recently vaccinated persons, corroborating earlier findings. Identifying which MuV epitopes are dominantly targeted in the mumps-specific CD8+ T- response is an important step towards better understanding in the discrepancies between natural infection or vaccination-induced cell-mediated immune protection.

Seroprevalence of Measles and Mumps Antibodies Among Individuals With Cancer.

Importance: Although patients with cancer are at an increased risk of infection-related complications, few studies have characterized their vulnerability to measles and mumps. Given the recent outbreaks and increased community vaccine hesitancy, understanding measles and mumps immunity within this population is vital. Objectives: To identify a point prevalence estimate of protective measles and mumps antibodies among ambulatory patients with cancer. Design, Setting, and Participants: In this cross-sectional study, residual clinical plasma samples were obtained from consecutive patients with cancer at Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center in Seattle, Washington, in August 2019. These samples were tested for measles and mumps IgG using a commercial enzyme-linked immunosorbent assay. Patients without cancer were excluded from the analysis. Exposures: Patient age, sex, self-reported race and ethnicity, primary disease, receipt of chemotherapy in the past 30 days before sample collection, hematopoietic cell transplant (HCT) history, and date of most recent intravenous immunoglobulin treatment were abstracted from electronic medical records. Main Outcomes and Measures: Measles and mumps IgG seroprevalence, defined as the proportion of patients with positive antibody test results, was measured overall and among the subgroups. Results: Of the 959 patients included in the analysis, 510 (53%) were male individuals and the mean (SD) age at sample collection was 60 (15) years. Most patients (576 [60%]) had a malignant solid tumor, and 383 patients (40%) had a hematologic malignant neoplasm; 146 patients (15%) had an HCT history. Overall, the seroprevalence of measles antibodies was 0.75 (95% CI, 0.72-0.78), and the seroprevalence of mumps antibodies was 0.62 (95% CI, 0.59-0.65). The lowest seroprevalences were among patients with a hematologic malignant neoplasm (0.63 for measles and 0.48 for mumps), those with a history of HCT (0.46 for measles and 0.29 for mumps), and those aged 30 to 59 years (0.49-0.63 for measles and 0.41-0.58 for mumps). Conclusions and Relevance: In this study, 25% of ambulatory patients with cancer lacked protective antibodies for measles and 38% lacked protective antibodies for mumps. Deficits in protective antibodies underscore patients' increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population.

Low immunity against vaccine preventable diseases in Turkish HIV cohort

Background/aim: HIV infection increase the risk of serious disease resulting from common vaccine-preventable infections. Vaccinations are particularly important for HIV infected adults. We aimed to investigate the immunity rates against measles, mumps, rubella, hepatitis A, B, and tetanus in newly diagnosed HIV patients. Materials and methods: Patients who admitted to outpatient clinics of three centers with newly diagnosed HIV infection, between 1 January 2015 and 31 June 2017 were included. Measles, mumps, rubella, varicella zoster virus, hepatitis A, hepatitis B, and tetanus antibody levels were measured by commercial diagnostic kits. Demographical and laboratory data of the patients were recorded. Results: Five hundred and twenty-three patients were enrolled in the study. Of the patients 87% were male (n = 455) and the mean age was 38 ± 13 years. Serology was available for measles 74.2% (388/523), mumps 73.8% (386/523), rubella 77.8% (407/523), hepatitis A 88.5% (463/523), hepatitis B 97.7% (511/523), tetanus 8.6% (45/523), and VZV 79.9% (418/523). Seropositivity was 82% for measles, 75.6% for mumps, 92.1% for rubella. Of the patients whom all three of the components of the MMR vaccine was tested, 37.7% (127/337) were susceptible at least one and needed the vaccine. Mean age was lower in patients who are nonimmune to measles and mumps (p = 0.008). Younger patients were also nonimmune for hepatitis A, while older patients were nonimmune for hepatitis B. Conclusion: In our study we found that rates of nonimmunity can increase up to one third of the patients even though there is a national vaccination program. Nonimmune individuals should be detected and vaccinated in line with recent guidelines and response should be monitored because of the possibility of impaired immunity and possible suboptimal response. National campaigns can be launched for adult immunization and physicians should be aware of the importance of adult immunization.

Mumps Orchitis: Clinical Aspects and Mechanisms.

The causative agent of mumps is a single-stranded, non-segmented, negative sense RNA virus belonging to the Paramyxoviridae family. Besides the classic symptom of painfully swollen parotid salivary glands (parotitis) in mumps virus (MuV)-infected men, orchitis is the most common form of extra-salivary gland inflammation. Mumps orchitis frequently occurs in young adult men, and leads to pain and swelling of the testis. The administration of MuV vaccines in children has been proven highly effective in reducing the incidence of mumps. However, a recent global outbreak of mumps and the high rate of orchitis have recently been considered as threats to male fertility. The pathogenesis of mumps orchitis remains largely unclear due to lack of systematic clinical data analysis and animal models studies. The alarming increase in the incidence of mumps orchitis and the high risk of the male fertility have thus become a major health concern. Recent studies have revealed the mechanisms by which MuV-host cells interact and MuV infection induces inflammatory responses in testicular cells. In this mini-review, we highlight advances in our knowledge of the clinical aspects and possible mechanisms of mumps orchitis.

Inadequate Measles, Mumps, Rubella, and Varicella Immunity Among Employees.

OBJECTIVES: The purpose of this cohort study was to evaluate measles, mumps, rubella (MMR), and varicella immunity among a population of adult employees receiving primary care in an employer-sponsored health center. METHODS: Participants were eligible for MMR and varicella immunity screening if they were an employee receiving primary care in an employer-sponsored health center between January 1, 2019 and November 1, 2020 who could not provide proof of immunization and 1) had it recommended by their provider, 2) specifically requested immunity testing (often because they had heard of measles outbreaks in their country of origin), or 3) were seen for an immigration physical for their Green Card application. RESULTS: Overall, 3494 patients were screened for their MMR immunity. Of these, 3057 were also screened for varicella immunity. Among these patients, 13.9% lacked measles immunity, 0.83% lacked immunity to all 3 components of MMR, and 13.2% lacked varicella immunity. Among the 262 patients who presented specifically for immunity screening, the rates of lacking immunity were higher for all conditions: 22.7% lacked measles immunity and 9.2% lacked varicella immunity. CONCLUSION: Given declines in immunizations during the COVID-19 pandemic, there is reason to be concerned that measles and varicella-associated morbidity and mortality may rise. Employers, especially those with large foreign-born populations or who require international travel may want to educate their populations about common contagious illnesses and offer immunity validation or vaccinations at no or low cost.

Serum Concentration of Antibodies to Mumps, but Not Measles, Rubella, or Varicella, Is Associated with Intake of Dietary Fiber in the NHANES, 1999-2004.

Treatment with prebiotics, a type of dietary fiber, was recently shown to increase antibody concentrations following influenza vaccination in a meta-analysis of clinical trials. In observational epidemiologic studies it is not possible to estimate intake of prebiotics, but quantifying intake of dietary fiber is routine. Our objective was to investigate the potential effect of dietary fiber on immunogenicity. We examined serum antibody concentrations (Measles, Mumps, Rubella, and Varicella) in relation to dietary fiber in more than 12,000 subjects in the U.S. National Health and Nutrition Examination Survey (NHANES) for the period 1999-2004. Data from one (1999-2002) or two (2003-2004) dietary recalls were used to calculate fiber intake. For Mumps the adjusted percentage difference in antibody concentration per interquartile range intake in energy-adjusted dietary fiber was 6.34% (95% confidence interval, 3.10, 9.68). Fiber from grain-based foods was more positively associated than fiber from other fiber-containing food groups. The association was slightly larger among subgroups with higher fiber intake, greater interquartile range in fiber intake, and less measurement error. Furthermore, based on the reliability of the diet recalls in 2003-2004, we calculated that the percentage difference per interquartile increment was substantially attenuated by measurement error. Dietary fiber may have a favorable influence on the immunogenicity of some vaccines or natural infections.

The Immunogenicity and Safety Profile for KM-248, a Combined Measles, Mumps, and Rubella Vaccine, and Its Noninferiority to the Measles Vaccine in Healthy Japanese Children: a Phase 3 Randomized Multicenter Single-Blind Clinical Trial.

The domestic combined measles-mumps-rubella (MMR) vaccine was withdrawn in Japan in 1993 following an outbreak of aseptic meningitis attributed to the mumps component of the cocktail. KM-248 is an MMR vaccine (M-M-R®II), manufactured by Merck & Co., Inc. (Kenilworth, NJ, USA) and registered and approved in 74 countries, but which has not been approved in Japan. This multicenter, randomized, single-blind study, was designed to evaluate the noninferiority of the KM-248 measles component in terms of immunogenicity when compared to the control measles vaccine already approved in Japan and the seroconversion rates for these three viruses following KM-248 administration. Vaccination with KM-248 in children aged 12-90 months (n = 178) induced robust immune responses to measles, mumps, and rubella viruses. The seroconversion rate for the measles virus by the measles component of KM-248 (n = 172) was shown to be non-inferior to that of the control measles vaccine (n = 85). No serious adverse reactions, such as aseptic meningitis or anaphylaxis, were observed. Fever is one of the most common adverse reactions associated with vaccination and was observed in approximately half of the participants. KM-248 administered to healthy Japanese children aged between 12 and 90 months demonstrated a comparable safety and efficacy profile to the control vaccine.

Impact of complement and difference of cell-based assay and ELISA in determination of neutralization capacity against mumps and measles virus.

Neutralizing antibodies against mumps and measles virus are considered a correlate of protection against these diseases. Measurement of neutralizing antibodies is mostly performed using plaque reduction neutralization assay or 50% cell culture infective dose (CCID50) neutralization assay, but there are attempts for measuring neutralizing antibodies using enzyme-linked immunosorbent assay (ELISA) which is simpler, but the literature data regarding its convenience are diverse. The role of complement and antibodies in neutralizing capacity of sera is not completely defined. Here, CCID50 neutralization assay and ELISA were used to determine the neutralization capacity against mumps and measles virus in human sera and therapeutic immunoglobulins (IVIGs). Results showed no correlation of neutralization titers obtained by CCID50 neutralization assay and IgG content obtained by ELISA for mumps or measles in human sera. Data showed some neutralization activity against measles virus and quite high against mumps virus of naïve guinea pig serum and that its addition increases neutralization capacity of IVIG and human sera against mumps and measles viruses. Heat inactivation of human sera reduced neutralization capacity against measles to small extent, and substantially against mumps virus. There is a significant impact of complement in measurement of neutralization capacity against mumps virus.

A longitudinal cohort study of childhood MMR vaccination and seizure disorder among American children.

BACKGROUND: Measles (rubeola) is a highly contagious infectious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) to prevent measles. This retrospective longitudinal cohort study evaluated childhood MMR vaccination and the risk of a seizure episode and seizure disorder. METHODS: The Independent Healthcare Research Database (IHRD) composed of records prospectively generated from Florida Medicaid was analyzed using SAS to identify persons continuously enrolled from birth for 120 months. Two cohorts were examined: 23,486 persons received at least one dose of MMR vaccine between 12 and 17 months (vaccinated) and 41,725 persons not receiving a measles-containing vaccine (unvaccinated). The daily incidence rate of an initial seizure episode (ICD-9 code: 780.3x) and seizure disorder (ICD-9 code: 345.xx) following an initial seizure episode diagnoses were examined using Cox proportional hazards ratio (HR) and time-trend models post-MMR vaccination compared to unvaccinated persons and in a self-controlled case-series (SCCS). RESULTS: The daily incidence rate of an initial seizure episode diagnosed from 6 to 11 days post-MMR vaccination in comparison to 12 to17 months among unvaccinated persons was significantly increased (unadjusted HR = 5.73, p < 0.0001 and adjusted HR = 5.94, p < 0.0001) in HR models. The daily incidence rate of an eventual seizure disorder diagnosis among those diagnosed with an initial seizure episode from 6 to 11 days post-MMR vaccination was significantly increased (unadjusted HR = 17.7, p < 0.01 and adjusted HR = 17.4, p < 0.01) in comparison to the daily incidence rate of an eventual seizure disorder diagnosis among those diagnosed with an initial seizure episode from 12 to 17 months among unvaccinated persons. Time-trend analyses revealed a significantly increased rate ratio (RR) for an initial seizure episode (RR = 4.64, p < 0.0001) and seizure disorder (RR = 5.51, p < 0.0001) diagnoses. Time-trend SCCS analyses revealed a significantly increased daily incidence rate of an initial seizure episode (RR = 3.80, p < 0.0001) when comparing periods from 6 to 11 days post-MMR vaccination to 49-60 days post-MMR vaccination. The incidence rate of an eventual seizure disorder diagnosis among those with an initial seizure episode diagnosis from 6 to 11 days post-MMR vaccination compared to 49-60 days post-MMR vaccination was significantly increased (RR = 4.15, p < 0.01). CONCLUSION: Seizure episode and seizure disorder are rare consequences of routine childhood MMR vaccination.

Mumps Outbreaks in Vaccinated Populations-Is It Time to Re-assess the Clinical Efficacy of Vaccines?

History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity.

[Is complete immunity against measles a realistic target for patients with rheumatic diseases and how can it possibly be achieved?] / Ist komplette Immunität gegen Masern bei Patienten mit rheumatischen Erkrankungen ein realistisches Ziel, und wie ist es möglicherweise zu erreichen?

Measles outbreaks occur rather frequently in Germany. Patients with chronic inflammatory diseases are often treated with immunosuppressants. A recent study showed that about 7% of such patients are not protected against measles according to the lack of documentation in the vaccination card or the absence of protective antibodies. The Standing Committee on Immunization (STIKO) recommends a first vaccination against measles as a measles-mumps-rubella combined vaccination (MMR) in children aged 11-14 months and a second vaccination at 14-23 months. For adults born after 1970, vaccination against measles is recommended if they have not yet been vaccinated against measles or have only been vaccinated once against measles or if their vaccination status is unclear. In April 2019, STIKO published instructions for vaccinations recommended for immunodeficiency. Since March 1, 2020, measles vaccination have been compulsory in Germany.

Australian mumps serosurvey 2012-2013: any cause for concern?

OBJECTIVES: To determine population-level immunity to mumps in Australia. METHODS: We tested randomly selected specimens from people aged 1-49 years using the Enzygnost anti-parotitis IgG enzyme immunoassay from an opportunistically collected serum bank in 2012-2013. Weighted estimates of the proportion seropositive and equivocal for mumps-specific IgG antibody were determined by age group and compared with two previous national serosurveys conducted in 2007-2008 and 1997-1998. RESULTS: Overall, 82.1% (95% CI 80.6-83.5%) of 2,729 specimens were positive or equivocal for mumps-specific IgG antibodies (71.1% positive [95% CI 69.4-72.9%]; 10.9% equivocal [95% CI 9.8-12.2%]). The proportion positive or equivocal was higher in 2012-2013 (82.1%) than in 2007-2008 (75.5%) and 1997-1998 (72.5%), but varied by age. The proportion positive or equivocal in 2012-2013 was above 80% for all age groups older than 1 year except for 30-34 year olds, corresponding to the 1978-1982 birth cohort previously identified as most likely to have missed out on a second MMR vaccine dose. CONCLUSION: Seropositivity to mumps in 2012-2013 was well-maintained compared with previous serosurveys. Low mumps notifications over this period in Australia suggest an absence of community-based transmission of mumps infection in the general population, but recent outbreaks among Aboriginal adolescents and young adults in close-contact settings, despite high 2-dose MMR coverage, suggest that seroprotection may be insufficient in other similar settings in Australia.Seropositivity to mumps in 2012-2013 was well-maintained compared with previous serosurveys. Low mumps notifications over this period in Australia suggest an absence of community-based transmission of mumps infection in the general population, but recent outbreaks among Aboriginal adolescents and young adults in close-contact settings, despite high 2-dose MMR coverage, suggest that seroprotection may be insufficient in other similar settings in Australia.

Effect of change in cell substrate on the critical quality attributes of L-Zagreb Mumps vaccine manufactured using parallel plate bioreactor.

Leningrad-Zagreb strain of mumps vaccine virus was grown on two different cell substrates viz. MRC-5 cells and Vero cells besides its original cell substrate i.e. Chicken Embryo Cells. Homogeneous virus pools prepared from each set of experiments were then lyophilized as per standard in-house protocol. Critical Quality Attributes (CQAs) such as the titer of the bulk vaccine and potency and stability of the lyophilized vaccine were then estimated using the CCID50 method to understand the lyophilization losses and thermal losses respectively in the vaccine. Another CQA viz. the genetic homogeneity of the vaccine was also tested using the single base extension method for identifying the nucleotides present at the three known locations of single nucleotide polymorphism (SNP). Comparison of CQA results across different cell substrates indicated encouraging results for Vero cell grown L-Zagreb virus compared to the MRC-5 cells grown L-Zagreb mumps virus. Significant improvement in productivity was also observed in the dynamic culture conditions compared to the static culture conditions. Progressive work in this research area can lead to development of a cGMP manufacturing process for mumps vaccine with easy scale up potential in future.

Rapid and sensitive determination of neomycin and kanamycin in measles, mumps, and rubella vaccine via high-performance liquid chromatography-tandem mass spectrometry using modified super-paramagnetic Fe3O4 nanospheres.

A simple magnetic dispersive solid-phase extraction (MDSPE) methodology based on mesoporous Fe3O4@ succinic acid nanospheres and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed to determine kanamycin (KNM) and neomycin (NEO) contents in Measles, Mumps, and Rubella (MMR) vaccine products. The monodispersed mesoporous Fe3O4 nanospheres with self-assembled carboxyl terminated shell have been prepared via a simple solvothermal method. These as-synthesized mesoporous Fe3O4 nanospheres showed a high magnetic saturation value (Ms = 46 emu g-1) and large specific surface area (111.12 m2 g-1) which made them potential candidates as sorbents in magnetic solid-phase extraction. The adsorption experimental data fitted well with the Freundlich-Langmuir isotherm and followed a pseudo-second-order kinetic model. Moreover influential parameters on extraction efficiency were investigated and optimized. Under optimal conditions, the limits of detection for KNM and NEO were 1.0 and 0.1 ng mL-1, respectively. Recovery assessments using real samples exhibited recoveries in the range of 96.0 ± 4.3 to 101.5 ± 7.1 %, with relative standard deviations of <10.7% (for intra- day) and <14.6% (for inter- day). The proposed method was successfully applied for different spiked and un-spiked MMR vaccine samples. The presented extraction method provides a fast, selective, robust and practical platform for the detection of KNM and NEO in MMR vaccine samples.

Waning immunity and re-emergence of measles and mumps in the vaccine era.

Vaccine-preventable diseases (VPD) including measles and mumps have been re-emerging in countries with sustained high vaccine coverage. For mumps, waning immunity has been recognized as a major contributor to recent outbreaks. Although unvaccinated individuals account for most cases in recent measles outbreaks, the role of immune waning remains unclear. Accumulating serological and epidemiological evidence suggests that natural immunity induced by infection may be more durable compared to vaccine-induced immunity. As the proportion of population immunity via vaccination gradually increases and boosting through natural exposures becomes rare, risk of outbreaks may increase. Mechanistic insights into the coupled immuno-epidemiological dynamics of waning and boosting will be important to understand optimal vaccination strategies to combat VPD re-emergence and achieve eradication.