Jeryl Lynn Mumps Research Articles

Vaccines for measles, mumps, rubella, and varicella in children.

Vaccines for measles, mumps, rubella, and varicella in children.

Genetic Analysis Reveals Differences in CD8+ T Cell Epitope Regions That May Impact Cross-Reactivity of Vaccine-Induced T Cells against Wild-Type Mumps Viruses.

Nowadays, mumps is re-emerging in highly vaccinated populations. Waning of vaccine-induced immunity plays a role, but antigenic differences between vaccine and mumps outbreak strains could also contribute to reduced vaccine effectiveness. CD8+ T cells play a critical role in immunity to viruses. However, limited data are available about sequence variability in CD8+ T cell epitope regions of mumps virus (MuV) proteins. Recently, the first set of naturally presented human leukocyte antigen Class I (HLA-I) epitopes of MuV was identified by us. In the present study, sequences of 40 CD8+ T cell epitope candidates, including previously and newly identified, obtained from Jeryl–Lynn mumps vaccine strains were compared with genomes from 462 circulating MuV strains. In 31 epitope candidates (78%) amino acid differences were detected, and in 17 (43%) of the epitope candidates the corresponding sequences in wild-type strains had reduced predicted HLA-I-binding compared to the vaccine strains. These findings suggest that vaccinated persons may have reduced T cell immunity to circulating mumps viruses due to antigenic differences.

Vaccines for measles, mumps, rubella, and varicella in children.

Vaccines for measles, mumps, rubella, and varicella in children.

A Third Dose of Measles-Mumps-Rubella Vaccine to Improve Immunity Against Mumps in Young Adults.

Waning of vaccine-induced immunity is considered to play a central role in the reemergence of mumps among vaccinated young adults. The aim of the present study was to investigate antibody responses and safety of a third dose of measles-mumps-rubella vaccine (MMR-3) in 150 young adults. Antibody levels were related to a surrogate of protection based on preoutbreak serum antibody levels in 31 persons with and 715 without serological evidence of mumps. Mumps virus-specific immunoglobulin G (IgG) antibody responses and mumps virus-neutralizing antibody responses (based on the focus-reduction neutralizing test) against both the Jeryl Lynn mumps virus vaccine strain (hereafter, the "vaccine strain") and the MuVi/Utrecht.NLD/40.10 outbreak strain (hereafter, the "outbreak strain") were determined, and vaccine safety was evaluated. Four weeks following MMR-3 receipt, levels of IgG, anti-vaccine strain, and anti-outbreak strain antibodies increased by a factor of 1.65, 1.34, and 1.35, respectively. Although antibody levels decreased 1 year later, they were still above the baseline level by a factor of 1.37, 1.15, and 1.27, respectively. Based on the surrogate protective antibody cutoff, significantly more participants were protected against mumps virus infection up to 1 year after vaccination (ie, they had antibody levels above the presumed threshold for herd immunity). MMR-3 receipt increased antibody levels that may protect against mumps virus infection for longer than previously assumed and is expected to be a good and safe intervention for controlling a mumps outbreak. 2016-001104-36; NTR5911.

Jeryl-Lynn Mumps Vaccine-Derived Parotitis Diagnosed in the Setting of a Recent Mumps Outbreak

Abstract This report details the diagnosis of Jeryl-Lynn vaccine-derived parotitis in a medical student after receiving the measles-mumps-rubella vaccine. Diagnostic verification of mumps vaccine-induced disease was a priority given a recent mumps outbreak affecting 13 students in the undergraduate university and another medical student at the same university's affiliated medical school. Ultimately, genotypic analysis of the medical student's buccal mumps polymerase chain reaction sample confirmed vaccine-induced disease.

In vitro and in vivo growth alter the population dynamic and properties of a Jeryl Lynn mumps vaccine

Mumps vaccines are live attenuated viruses. They are known to vary in effectiveness, degree of attenuation and adverse event profile. However, the underlying reasons are poorly understood. We studied two closely related mumps vaccines which originate from the same attenuated Jeryl Lynn-5 strain but have different efficacies. Jeryl Lynn-Canine Kidney (JL-CK), produced on primary canine kidney cells, is less effective than RIT4385, which is produced on chicken embryo fibroblasts. JL-CK and RIT4385 could be distinguished by a number of in vitro and in vivo properties. JL-CK produced heterogeneous, generally smaller plaques than RIT4385, but gave 100-fold higher titres when grown in cells and showed a higher degree of hydrocephalus formation in neonatal rat brains. Sanger sequencing of JL-CK identified 14 regions of heterogeneity throughout the genome. Plaque purification of JL-CK demonstrated the presence of five different Jeryl Lynn-5 variants encompassing the 14 mutations. One JL-CK mutation was associated with a small plaque phenotype, the effects of the others in vitro or in vivo were less clear. Only 4% of the JL-CK population corresponded to the parental Jeryl Lynn-5 strain. Next generation sequencing of JL-CK and virus before and after growth in cell lines or neonatal rat brains showed that propagation in vitro or in vivo altered the population dramatically. Our findings indicate that growth of JL-CK in primary canine kidney cells resulted in the selection of a mixture of mumps virus variants that have different biological properties compared to the parent Jeryl Lynn-5 virus. We also report three previously unknown heterogenic regions within the N gene of the RIT4385 vaccine.

Vaccines for measles, mumps and rubella in children

Vaccines for measles, mumps and rubella in children

Vaccines for measles, mumps and rubella in children.

Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. To assess the effectiveness and adverse effects associated with the MMR vaccine in children up to 15 years of age. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed (July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011). We used comparative prospective or retrospective trials assessing the effects of the MMR vaccine compared to placebo, do nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age. Two review authors independently extracted data and assessed methodological quality of the included studies. One review author arbitrated in case of disagreement. We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella.The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections. The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.

Safety and Antibody Responses to Aerosolized MMR II Vaccine in Adults: An Exploratory Study

Background: There have been no reported studies involving aerosol immunization with 2 of the 3 components of MMR II vaccine—Attenuvax measles vaccine and Jeryl-Lyn mumps vaccine. Objective: To evaluate the safety and antibody responses to aerosolized Attenuvax measles strain, Jeryl Lynn mumps strain and RA 27/3 rubella component of an MMR vaccine in adults, before assessing the booster administration of this vaccine in children. Methods: A pilot study to evaluate safety and antibody responses of MMR II (Merch Sharp & Dhome Corp., Whitehouse Station, NJ 08889, USA) components administered by aerosol was carried out in 27 healthy adults of 21 to 38 years of age. All participants were followed-up during 28 days following immunization for detection of clinical adverse events. Immune response was evaluated by plaque reduction neutralization test for measles, and commercial ELISA kits for rubella and mumps. Results: Only mild clinical adverse events were noted. Despite high levels of baseline seropositivity to all vaccine components, seroresponses to measles, rubella and mumps occurred in 44%, 15% and 41%, respectively. Conclusions: These outcomes compare favorably with earlier studies of other MMR vaccines given by aerosol. Further evaluations on safety and booster immune response should be performed in children.

Molecular differences between two Jeryl Lynn mumps virus vaccine component strains, JL5 and JL2

The Jeryl Lynn (JL) vaccine against mumps virus (MuV) contains two components, MuVJL5 and MuVJL2, which differ by over 400 nt. Due to the occurrence of bias in the direction of mutation, these differences and those found in nucleotide sequences of different isolates of the minor component in the vaccine (MuVJL2) might be due to the effect of ADAR-like deaminases on MuV grown in tissue-cultured cells. A molecular clone of MuVJL2 (pMuVJL2) and MuVJL2-specific helper plasmids were constructed in order to investigate molecular interactions between MuVJL5 and MuVJL2, to augment the existing molecular clone of MuVJL5 (pMuVJL5) and MuVJL5-specific helper plasmids. Genome and mRNA termini of MuVJL2 were characterized, and an unusual oligo-G insertion transcriptional editing event was detected near the F mRNA polyadenylation site of MuVJL2, but not of MuVJL5. Genes encoding glycoproteins of rMuVJL2 and rMuVJL5 have been exchanged to characterize the oligo-G insertion, which associated with the specific sequence of the F gene of MuVJL2 and not with any other genes or the RNA-dependent RNA polymerase of strain MuVJL2. The results indicate that a single G-to-A sequence change obliterates the co-transcriptional editing of the F mRNA and that this oligo-G insertion does not affect the growth of the virus.

Antibody Induced by Immunization with the Jeryl Lynn Mumps Vaccine Strain Effectively Neutralizes a Heterologous Wild‐Type Mumps Virus Associated with a Large Outbreak

Recent mumps outbreaks in older vaccinated populations were caused primarily by genotype G viruses, which are phylogenetically distinct from the genotype A vaccine strains used in the countries affected by the outbreaks. This finding suggests that genotype A vaccine strains could have reduced efficacy against heterologous mumps viruses. The remote history of vaccination also suggests that waning immunity could have contributed to susceptibility. To examine these issues, we obtained consecutive serum samples from children at different intervals after vaccination and assayed the ability of these samples to neutralize the genotype A Jeryl Lynn mumps virus vaccine strain and a genotype G wild-type virus obtained during the mumps outbreak that occurred in the United States in 2006. Although the geometric mean neutralizing antibody titers against the genotype G virus were approximately one-half the titers measured against the vaccine strain, and although titers to both viruses decreased with time after vaccination, antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralized the outbreak-associated virus at all time points tested.

Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer

Oncolytic viruses are promising cytoreductive agents for cancer treatment but extensive human testing will be required before they are made commercially available. Here, we investigated the oncolytic potential of two commercially available live attenuated vaccines, Moraten measles and Jeryl-Lynn mumps, in a murine model of intraperitoneal human ovarian cancer and compared their efficacies against a recombinant oncolytic measles virus (MV-CEA) that is being tested in a phase I clinical trial. The common feature of these viruses is that they express hemagglutinin and fusion therapeutic proteins that can induce extensive fusion of the infected cell with its neighbors, resulting in death of the cell monolayer. In vitro, the three viruses caused intercellular fusion in human ovarian cancer cells but with marked differences in fusion kinetics. MV-CEA was the fastest followed by Jeryl-Lynn mumps virus while Moraten measles virus was the slowest, although all viruses eventually caused comparable cell death 6 days postinfection. Tumor-bearing mice treated with 10(6) or 10(7) pfu (one thousand times the vaccine dose) of each of the three viruses responded favorably to therapy with significant prolongations in survival. All three viruses demonstrated equivalent antitumor potency. Commercially available Moraten measles and Jeryl-Lynn mumps vaccines warrant further investigation as potential anticancer agents.

Measles, mumps, rubella vaccine (Priorix; GSK-MMR): a review of its use in the prevention of measles, mumps and rubella.

GSK-MMR (Priorix) is a trivalent live attenuated measles, mumps and rubella (MMR) vaccine which contains the Schwarz measles, the RIT 4385 mumps (derived from the Jeryl Lynn mumps strain) and the Wistar RA 27/3 rubella strains. GSK-MMR as a primary vaccination demonstrated high immunogenicity in clinical trials in >7500 infants aged 9-27 months, and was as immunogenic as Merck-MMR (MMR II). However, antimumps seroconversion rates and geometric mean titres (GMTs) were significantly higher in infants receiving GSK-MMR compared with Berna-MMR (Triviraten trade mark ) recipients. Coadministration of GSK-MMR with a varicella vaccine (Varilrix; GSK-MMR/V) did not significantly affect the immunogenicity of GSK-MMR. A persistent immune response to GSK-MMR has been demonstrated in follow-up data from several randomised trials. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1-2 years post-vaccination and were similar to those in Merck-MMR recipients. The immunogenicity of GSK-MMR was high, and similar to that of Merck-MMR, when used as a second dose in children aged 4-6 or 11-12 years who had received a primary vaccination with Merck-MMR in their second year of life. Although there are no protective efficacy data concerning the GSK-MMR vaccine to date, the rubella Wistar RA 27/3 rubella and Schwarz measles strains have well established protective efficacy; the new RIT 4385 mumps strain is expected to afford similar protection from mumps to that achieved with mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR). GSK-MMR was well tolerated as a primary or secondary vaccination, and in most clinical studies comparing GSK-MMR with Merck-MMR as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events (e.g. pain, swelling and redness). The incidence of local adverse events with GSK-MMR, GSK-MMR/V or Berna-MMR was similar. GSK-MMR and Merck-MMR were associated with similar rates of fever, rash and parotid gland swelling, but Berna-MMR was associated with a lower incidence of fever. In conclusion, GSK-MMR is a highly immunogenic MMR vaccine with good tolerability. In clinical trials, the immunogenicity of GSK-MMR was similar to that of Merck-MMR, and the mumps component was more effective at eliciting seroprotection than that of Berna-MMR. Furthermore, GSK-MMR causes fewer injection-site adverse events than Merck-MMR. As such, GSK-MMR is an attractive alternative for immunisation against measles, mumps and rubella.

Safety and characterization of the immune response engendered by two combined measles, mumps and rubella vaccines

We performed a randomized trial to compare the safety and immunogenicity of two combined measles, mumps and rubella vaccines in healthy children 14–24 months of age. Triviraten Berna ® Vaccine (Swiss Serum and Vaccine Institute), contains the Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and the Wistar RA 27 3 rubella strain while MMR-Vax ® (Merck, Sharp & Dohme, West Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl Lynn mumps strain and the Wistar RA 27 3 rubella strain. Immunization with Triviraten Berna ® was associated with a significantly lower incidence of swelling and redness at the injection site in addition to a reduced rate of fever compared with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components were comparable in all tests used. However, seroconversion for the mumps vaccine component was test-dependent. Using an ELISA, the seroconversion rate following immunization with MMR-Vax was significantly ( P < 0.01) higher than for Triviraten Berna. In contrast, nearly identical rates were obtained using an indirect immunofluorescence test. Both vaccines were equally effective at engendering antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA antibody titers against measles and mumps virus were higher following immunization with MMR-Vax while that for rubella was higher after immunization with Triviraten Berna. A small number ( N = 13) of adolescents immunized either with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and various humoral and cellular response parameters to the measles and mumps vaccine components analyzed. While few subjects mounted a humoral antibody response to measles, most likely due to elevated baseline titers, there was a marked lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher both at baseline and after reimmunization in subjects who received MMR-Vax for primary immunization. However, there was no difference in either neutralizing titer or proliferative response in subjects primed with MMR-Vax or Triviraten Berna either before or after reimmunization.

Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project

To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population. A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case. The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses). Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.

Antibodies to measles, mumps and rubella in UK children 4 years after vaccination with different MMR vaccines

Persistence of antibodies 4 years after vaccination with measles, mumps and rubella (MMR) vaccine from three different manufacturers was compared in 475 children who received a single injection of vaccine when aged 12–18 months. Antibodies to measles and mumps were measured using a plaque reduction neutralisation assay; rubella antibodies were measured by radial haemolysis and latex agglutination. Children given MMR vaccine containing the Urabe mumps strain were less likely to be antibody negative than those given the Jeryl Lynn mumps strain ( 39 266 , 15% vs 39 204 , 19%, p=0.048). However, the relatively high proportions in both groups without detectable mumps neutralising antibody suggests the probable need for a second dose in order to achieve mumps elimination. No significant differences were found in the proportions with detectable antibody to measles between vaccines containing the Schwarz and the Enders-Edmonston strains. Overall, only 3% of vaccinees were without detectable measles antibody, although a further 28% had a level below 200 mille International Units, the putative protective level for clinical measles. Geometric mean titres (GMTs) to measles were twofold higher in girls vaccinated after than before 14 months of age; GMTs in boys were intermediate and showed no age effect. Over 99% of vaccinees were seropositive to rubella, confirming the excellent immunogenicity of the RA 27 3 rubella strain and the potential for elimination of rubella with a single dose strategy.

Persistence of Antibody After Administration of Monovalent and Combined Live Attenuated Measles, Mumps, and Rubella Virus Vaccines

Hemagglutination-inhibiting antibodies were retained in comparable levels eight years after vaccination with Enders' original Edmonston and more attenuated Moraten (Attenuvax) and Schwarz line measles vaccines. Neutralizing antibody persisted without substantial decline in titer for at least 9.5 years after administration of Jeryl Lynn mumps virus vaccine (Mumpsvax). Antibodies were retained without important decline in children and adults for at least 7.5 and 7 years, respectively, after administration of HPV-77 duck-modified rubella vaccine (Meruvax). The patterns of antibody persistence 7.5 years after administration of combined measles-mumps-rubella (M-M-R) and mumps-rubella (Biavax) vaccines, 6 years after administration of measles-rubella vaccine (M-R-VAX), and 4 years after administration of measles-mumps vaccine (M-M-VAX) were the same as for the monovalent vaccines, indicating no alteration in the retention of immunity. Subclinical reinfection evidenced by increase in homologous antibody titer was observed to follow vaccination the same as occurs after natural infection.

PERSISTENCE OF IMMUNITY FOLLOWING MONOVALENT AND COMBINED LIVE MEASLES, MUMPS, AND RUBELLA VIRUS VACCINES

Neutralizing antibody following Jeryl Lynn mumps virus vaccine persisted for at least six years after vaccination without substantial decline in titer, and protective immunity was solidly retained through the sixth observation year. Hemagglutination-inhibiting antibodies following vaccination with Enders' original Edmonston and more attenuated Moraten and Schwarz lines measles vaccines were retained in comparable level through the fourth year. Antibody following HPV-77 duck rubella vaccine was retained without important decline for at least 3½ years. The pattern for antibody persistence following combined measles-mumps-rubella and mumps-rubella vaccine measured at three years and for measles-rubella vaccine measured at two years was the same as for the monovalent vaccines indicating no alteration in the retention of immunity. None of the children in this study lost his antibody completely. Subclinical reinfection evidenced by antibody increase was commonly seen in vaccinated persons.

Infants' responses to live, attenuated, B level, Jeryl Lynn mumps vaccine.

A study was designed to better characterize the serological responses of infants in the second year of life to live, attenuated, B level, Jeryl Lynn mumps-virus vaccine given singly since previous studies with small numbers had implied poorer seroconversion ratios in this age group. Of the 88 infants 12 to 24 months of age, 17 (or 19%) were shown to have had prior infection with the mumps virus. Seroconversion rates in the 71 infants who were initially seronegative were comparable to those reported in other children and adults. The study clearly confirms the feasibility of administering the mumps-virus vaccine either singly or in combination to infants greater than or equal to 12 months of age.

MEASUREMENT OF IMMUNITY FOLLOWING LIVE MUMPS (5 YEARS), MEASLES (3 YEARS), AND RUBELLA (2½ YEARS) VIRUS VACCINES

Data are presented to indicate persistence of immunity for at least 5 years after Jeryl Lynn mumps vaccine, 3 years after Moraten line measles vaccine, arid 2½ years after HPV-77 duck cell vaccine. Antibody retention was roughly the same following Enders' original, Moraten and Schwarz vaccines.