Jeryl Lynn Strain Research Articles

Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1−/− mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.

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

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

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

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

Impact of the MMR vaccine on the incidence of mumps in the Community of Madrid and evaluation of the effectiveness of the Jeryl-Lynn strain. Years 1998–2016

IntroductionMumps is characterized by parotid inflammation and fever and is preventable by vaccination with MMR vaccine. The objective of the study is to assess the impact and effectiveness of the vaccine. Material and methodsCases notified to the Notifiable Disease System between 1998 and 2016 were used for the study. The vaccine effectiveness (VE) was calculated in cohorts vaccinated with two doses of Jeryl-Lynn, and the impact was calculated by comparing incidences by age and by Rubini (1995–1998) and Jeryl-Lynn (1999–2002) cohorts during the periods 1998–2004, 2005–2009 and 2010–2015. The incidences for age group and period were compared with the previous period and the incidences for cohorts were compared within a period with incidence ratios (IR) using Poisson models. The VE was estimated using the screening method using logistic regression models. Results13,816 cases were reported. The incidence in 2005–2009 was higher than in 1998–2004 (IR: 1.46, 95% CI: 1.40–1.53), and it remained stable in 2010–2015 (IR: 0.99, 95% CI: 0.95–1.03). The average incidence rate of the Rubini cohort was 69.43 and the Jeryl-Lynn cohort was 32.24. The IR was 0.25 (95% CI: 0.22–0.29), 0.55 (95% CI: 0.49–0.61) and 0.88 (95% CI: 0.76–1.00) for each period respectively. 2574 cases were included in the VE study. EV decreased over time reaching not significant values after seven years of follow-up (VE: 55%, 95% CI: 82 to −12%). ConclusionsParotiditis behavior is characterized by fluctuations, changes in presentation and a decrease in VE.

Parotiditis vírica infecciosa: revisión, panorama epidemiológico y retos

<p><span>El virus de la parotiditis (MuV) es el agente etiológico de una parotiditis aguda benigna vírica, se trasmite por gotas respiratorias, incuba de 12 a 25 días, los síntomas se presentan de 16 a 18 días tras la exposición y el principal órgano afectado son las glándulas parótidas en las que se produce una inflamación local e intensa; la complicación más severa es la orquitis, la cual se presenta en hombres pospúberes. La serología es el método más simple para confirmar la infección del MuV y el inmunoensayo enzimático es la prueba más comúnmente utilizada. Esta enfermedad no cuenta con un tratamiento específico; la prevención específica es la vacuna, la cual está compuesta por virus vivos atenuados de la cepa Jeryl Lynn y tiene una eficacia de 88%. Desde 2012, se han reportado incrementos en el número de casos de parotiditis, la incidencia, el número de brotes y la proporción de casos asociados a brotes, por lo que se describe, a grandes rasgos, la parotiditis vírica infecciosa, su situación en el mundo y en México y los retos de la vacunación.</span></p>

Immunogenicity and Safety of an F-Genotype Attenuated Mumps Vaccine in Healthy 8- to 24-Month-Old Children.

Mumps vaccine immunizations have reduced the incidence of this disease. With the variation of mumps circulating strain, novel vaccine strains are always important. A 2-center parallel, randomized, double-blind noninferiority trial was performed to compare an F-genotype attenuated mumps vaccine (SP strain) to the A-genotype vaccine (S-79, Jeryl-Lynn strain) in 1080 healthy children aged 8-24 months in Hubei, China. Participants were randomly assigned to receive a high or low dose of the SP or S79 vaccine and then assessed clinically at 30 minutes and 1-28 days postinoculation. No differences in local or systemic reactivity were observed. A similar incidence of severe adverse events associated with the vaccine was observed in the high-dose group and the positive control group. Based on throat swab collections, no viral shedding was present at the 4th and 10th days in any group. Neutralizing and hemagglutination-inhibiting antibody assays with the F- or A-genotype strains showed similar trends in geometric mean titers in the high-dose SP and S79 groups. Increased cytotoxic T lymphocyte responses were observed in all groups. The F-genotype attenuated mumps vaccine is safe, offers immunogenicity against a homologous virus, and is noninferior to the A-genotype vaccine in 8- to 24-month-old children.

Vaccine waning and mumps re-emergence in the USA

BackgroundFollowing decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses.MethodsWe pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape.ResultsWe estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination.ConclusionThe resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination.Disclosures J. Lewnard, Pfier: Grant Investigator, Research grant

Genetic characteristics of mumps viruses isolated in Korea from 2007 to 2012

Mumps is a vaccine-preventable viral disease. Despite vaccine coverage of >95%, the incidence of mumps has increased in Korea since 2007. This study aimed to genetically characterize mumps virus (MuV) strains that circulated in Korea between 2007 and 2012 to determine the factors underlying mumps outbreaks. MuV was isolated from 175 clinical specimens between 2007 and 2012 in Korea. Upon analysis of the SH gene in Korean mumps virus isolates, three different genotypes were identified: I, H, and F. The MuV genotypes I and H co-circulated in Korea, and eight isolates of Korean genotype F were found within the same time period in 2008. An analysis of HN amino-acid sequence data showed that Korean isolates had no changes in their glycosylation sites. At putative neutralizing epitope sites, the Jeryl-Lynn strain showed 4-5 different amino acid sequences from those observed in Korean isolates. Korean isolates of genotypes I and H shared distinctive point mutations on putative neutralizing epitope positions in each genotype. This report describes the genetic characteristics of MuV strains circulating in Korea and provides information on endemic mumps infections. This information may be important to help prevent mumps and control outbreaks of mumps in Korea. J. Med. Virol. 88:1479-1486, 2016. © 2016 Wiley Periodicals, Inc.

Molecular detection and characterisation of mumps virus in cerebrospinal fluid in a Gauteng laboratory

The study aimed to determine the presence of mumps virus (MuV) in cerebrospinal fluid (CSF) specimens and to genetically characterise detected MuV strains. A real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the MuV F gene, and characterisation was performed by sequencing of the SH gene. Mumps virus was detected in 1.2% (3/260) of specimens. Phylogenetic analysis of one MuV strain revealed that it clustered with the Jeryl-Lynn and RIT4385 vaccine strains. As far as the authors could ascertain this is the first study to provide viral proof that these vaccine-like strains may be associated with aseptic meningitis.

Are cases of mumps in vaccinated patients attributable to mismatches in both vaccine T-cell and B-cell epitopes?

Resurgent mumps outbreaks have raised questions about the current efficacy of mumps vaccines. We have applied immunoinformatics techniques based on principal component analysis to evaluate patterns in predicted B-cell linear epitopes, MHC binding affinity and cathepsin cleavage in the hemagglutinin neuraminidase protein of vaccine strains and wild-type mumps isolates. We have mapped predicted MHC-peptide binding for 37 MHC-I and 28 MHC-II alleles and predicted cleavage by cathepsin B, L and S. By all measures we applied Jeryl-Lynn JL5 major strain is an outlier with immunomic features arising from a small number of amino acid changes that distinguish it from other virus strains. Individuals vaccinated with Jeryl-Lynn who are not exposed to wild-type virus until their protective antibody titer has waned may be unable to recall a protective immune response when exposed to wild-type virus. Dependence on serology to evaluate mumps vaccines may have overemphasized the conservation of one neutralizing antibody epitope, at the expense of monitoring other related changes in the HN protein that could affect recall responses.

Adverse events following a third dose of measles, mumps, and rubella vaccine in a mumps outbreak

During a 2009–2010 mumps outbreak in a New York State village, a third dose of measles, mumps, and rubella (MMR) vaccine was administered to children in three schools as a control measure. Information on local and systemic adverse events (AE) was collected by a self-report survey distributed to all children in grades 6–12. A comprehensive search for AE following MMR vaccination was conducted using physician records and the Vaccine Adverse Events Reporting System (VAERS). A literature search was performed for published reports pertaining to AE associated with mumps-containing vaccine, using the Jeryl-Lynn strain, from 1969 to 2011. A total of 1755 individuals received the third dose; 1597 (91.0%) returned the survey. Of those, 115 (7.2%) reported at least one local or systemic AE in the 2 weeks following vaccination. The most commonly reported AE were “pain, redness, or swelling at the injection site” (3.6%) and “joint or muscle aches” (1.8%). No serious AE were reported in the survey, physician records or through VAERS. The proportions of AE found in the present study were lower than or within the range of those reported in prior studies of first- and second-dose MMR vaccine studies. The results of this study suggest that a third dose of MMR vaccine administered in an outbreak setting is safe, with injection site reactions reported more frequently than systemic reactions. However, to assess risk for rare or serious AE after a third dose of MMR vaccine, longer term studies would be required.

Estudio de un brote epidémico de ámbito poblacional por el virus de la parotiditis G1 en JEREZ de la Frontera

ObjectivesTo characterize the mumps outbreak, assess the effectiveness of vaccines and discuss prevention and control measures. DesignObservational cross-sectional study of cases by person, place, and time. LocationCity Jerez de la Frontera and 8 Primary Care centres. ParticipantsA total of 116 cases of mumps were reported throughout seven months, with the last case in June 2008. MeasurementsMain outcomes: age, sex, place of study or work, symptoms start date, clinical description, complications, and genotype of virus isolation, history and vaccination compositions. Calculation of total vaccine effectiveness. Active case finding and contact studies were performed on the families, work places and leisure areas. ResultsThe mean age of the cases was 16.24 years(SD 10.6). The majority (68.96%) of the cases were children at school and 31.03% arose from family and work areas. Mumps vaccine coverage rates were above 90%. The complete vaccine effectiveness (2 doses); for those under 20 years-old it was: 99.84% (95% CI=99.77 - 99.89), being lower in schools with the highest attack rate, immunised with current vaccine from Jeryl Lynn strain: 71.01% (95% CI=55.85 80.97). Two doses of this strain were used in 13.79% of the cases. Susceptible populations were vaccinated at the start of the outbreak: 11,381 doses used in schools and 93 outside schools. ConclusionsAn outbreak of mumps virus G 1 population with high rates of mumps vaccine coverage, with areas with low vaccine effectiveness with current vaccine. Mass vaccination of population has contributed to the resolution of the outbreak.

Sequencing and analysis of mumps virus vaccine strain S79 Genome

Objective To analyze the genome sequencing of mumps virus strain 79 purified from working seeds plague and examine its phylogenetic relationship with wild type virus strain isolated in China,and to explore the efficacy of vaccine at molecular level.Methods Whole genome sequences of two substrains of S79(major and minor),were obtained with fragment amplification by RT-PCR.Genetic distances between S79 and strains identified in China were analyzed based on the phylogenic analysis of small hydrophobic protein(SH) sequences.Results The nucleotide homologies of two S79 substrains(major and minor),with a ratio of 2:5 during culture,with Jeryl Lynn(JL) strain were 99.7% and 100%,respectively.There were scattered non-homologous recombination between two substrains.The genetic distances between strain S79,which was genotype A,and wild type virus strain identified in China,which were genotype F,was 11.2% -20.0%.S79 live vaccine was composed of two substrains,major and minor component,which were highly similar to JL strain in their genome sequences,but different from JL in their ratios during culture.Conclusion Different from wild type virus strain identified in China,the genotype of S79 was A,and phylogenetically distant from other strains,which may account for the low efficacy of S79 live vaccine.The ratios of two substrains might also be of interest for further study of the vaccine protection and efficacy. Key words: Mumps virus; Plague purification; RT-PCR; Sequence analysis; S79

Effectiveness of Jeryl Lynn-containing vaccine in Spanish children

We evaluated the effectiveness of the Jeryl Lynn strain vaccine in a large outbreak of mumps in Navarre, Spain, 2006–2008. Each of the 241 cases of mumps occurring in children over 15 months of age born between 1998 and 2005 was compared with 5 controls individually matched by sex, birth date, district of residence and paediatrician. Vaccination history was obtained blindly from clinical records. Conditional logistic regression was used to obtain the matched odds ratios (ORs), and effectiveness was calculated as 1 − OR. Some 70% of cases had received one dose of measles–mumps–rubella vaccine, and 24% had received two doses. Overall vaccine effectiveness was 72% (95% CI, 39–87%). Two doses were more effective (83%; 54–94%) than a single dose (66%; 25–85%). Among vaccinated children, risk was higher in those who had received the first dose after 36 months of age (OR = 3.1; 1.2–8.4) and those who had received the second dose 3 or more years before study enrolment (OR = 10.2; 1.5–70.7). Early waning of immunity in children after the second dose may contribute to reduced vaccine effectiveness for mumps prevention.

Mumps Outbreaks in Vaccinated Populations: Are Available Mumps Vaccines Effective Enough to Prevent Outbreaks?

Increased reports of mumps in vaccinated populations prompted a review of the performance of mumps vaccines. The effectiveness of prior vaccination with 1 dose of vaccine ranged from 72.8% to 91% for the Jeryl Lynn strain, from 54.4% to 93% for the Urabe strain, and from 0% to 33% for the Rubini strain. Vaccine effectiveness after 2 doses of mumps vaccine was reported in 3 outbreaks and ranged from 91% to 94.6%. There was evidence of waning immunity, which is a likely factor in mumps outbreaks, aggravated by possible antigenic differences between the vaccine strain and outbreak strains. Inadequate vaccine coverage or use of the Rubini vaccine strain accounted for the majority of outbreaks reviewed; however, some outbreaks could not be prevented, despite high vaccination coverage with 2 doses of the Jeryl Lynn vaccine strain. Our findings indicate the need for more-effective mumps vaccines and/or for review of current vaccination policies to prevent future outbreaks.

Effectiveness of a vaccination program against mumps in Ukraine

Medical records and incidence data were analyzed retrospectively to document the epidemiology, clinical features, and outcomes of mumps in relation to vaccination status in the Lviv province of Ukraine over a 7.5-year period, beginning in 2000, when a second dose of mumps vaccine was introduced. Lviv, 1 of 27 provinces in western Ukraine, with a land area of 21,833 km(2), had a total population of about 2,555,834 in 2006. The initial success of the second dose introduction in 2000 in Ukraine was limited by a local outbreak of mumps in Lviv province in 2000-2002 due to a vaccine shortage; most cases were over the age of 7 years. The vaccine with the Leningrad-3 virus strain used before 2001 was then replaced by the triple vaccine "Priorix", with the RIT 4385 derivate of the Jeryl Lynn strain, Belgium. Orchitis and aseptic meningitis were associated with the Russian vaccine. Of the 10,894 reported cases, the most severe (367 cases, 3.4%) were hospitalized in the Lviv Hospital for Infectious Diseases. Admitted patients were predominantly male and over 14 years old. Of the 367 patients admitted to the Lviv Hospital for Infectious Diseases, 45.8% had been vaccinated (mostly by a first dose of Russian vaccine), 15.9% had not been vaccinated, and 38.1% had an unknown vaccination status. More mumps cases occurred in winter and spring than in summer and autumn. The clinical picture and complications (orchitis, pancreatitis, meningitis, and encephalitis) were typical of this disease. The vaccine shortage and an increase in the susceptible population among those who received the Russian vaccine contributed to the outbreak. The use of vaccine with a derivate of the Jeryl Lynn strain has resulted in a dramatic drop in mumps cases since 2002.

Molecular identification of two genotypes of mumps virus causing two regional outbreaks in Asturias, Spain

Background In spite of universal vaccination, several sporadic cases of mumps infection, which could produce outbreaks, are detected every year in different countries. Objective Mumps virus strains causing two regional outbreaks in Asturias (Spain) were phylogenetically characterized. Study design Mumps virus strains, which were detected in samples from patients belonging to two regional outbreaks in Asturias, were characterized by sequencing of the SH gene and further alignment to homologous sequences of representative strains of the different mumps genotypes. Results Two different strains (Ast/SP02 and Ast/SP07) were isolated. Sequence analysis revealed that while Ast/SP02 belonged to genotype H, Ast/SP07 was phylogenetically close to UK02-19, a reference strain for a new genotype. Both strains belonged to different genotypes from those used in the vaccination (Jeryl-Lynn strain is genotype A). Conclusion Mumps virus strains different from those used in vaccination program can cause mumps outbreaks even in vaccinated patients.

Brote por virus de la parotiditis G1 en la provincia de Almería en el año 2005

Despite high levels of triple MMR vaccinations being recorded on Spain, epidemic mumps outbreaks are still being reported. This study is aimed at describing an outbreak reported in the province of Almeria in 2005 and of evaluating the degree to which the vaccinated population was affected. Descriptive study of reported cases. Basic Health District, municipality, age, sex, type of population (Spanish-born and foreign), date of symptom onset, symptoms, complications, vaccination status, vaccine strain and diagnostic testing. disease reporting files, epidemiological surveys, microbiological data, vaccination card, District vaccine software and Andalusian Institute of Statistics demographic data. Rates per 100,000 inhabitants were calculated by age groups and population type. The Student's t-test was used for comparing means. A total of 145 cases from 17 municipalities were reported. A total 63.4% were males. The group showing the highest incidence was that of 10-14 years of age, with a rate of 405 per 100,000. The highest rate was among the Spanish-born population (128.7). A total of 52.4% of the cases were found to have been administered some dose of vaccine, 69.7% of them with two doses and 71.1% some Jeryl Lynn strain. Mumps virus was confirmed in 43 cases, the G1 genotype having been identified in 6 cases. An outbreak of G1 genotype mumps virus is confirmed, the Spanish-born population of different age groups having been affected to a greater extent. Over half of the cases were vaccinated individuals.

Brote de parotiditis vírica en un colegio de Bizkaia en 2006

Outbreaks of parotiditis have recently been recorded in Spain and in other developed countries. The possible reasons currently under consideration are the low degree of immunization coverage among the populations involved and/or the low degree of effectiveness of the vaccine strains employed. This study describes one outbreak of parotiditis having occurred in Bizkaia and assesses, the effectiveness of the vaccine strains and the usefulness of the diagnostic tests currently used. Those cases having compatible clinical symptoms and an epidemiological link within the period under study (February-May 2006) were labeled as cases. Blood samples were taken to study IgM and IgG and saliva for genotype and RNA detection. The immunization status and the strain used were found through the vaccine distribution records. A univariate analysis was conducted on the data and relative risks calculated according to the vaccine strains used. A total of 63 cases were detected, 52 being students from one school. Fifty percent were 9-13 years of age. A total of 88.5% of the cases detected at the school had been properly immunized. The IgM sensitivity was 9%, PCR sensitivity being 37%. The relative risk of those students immunized with an initial dose of Rubini strain as compared to those immunized with Jeryl-Lynn strain was 3.8 (95% CI:2.27-6.49). The high degree of immunization coverage does not prevent outbreaks from occurring in places having a high degree of exposure. The IgM reveals itself to be sensitive to a very small degree for the diagnosis of parotiditis. It seems necessary that the current immunization strategies and diagnostic methods be reconsidered.

Development and biological properties of a new live attenuated mumps vaccine

To develop a new live attenuated mumps vaccine, a wild mumps Y7 strain isolated from a patient who developed mild parotitis was treated with nitrosoguanidine and ultraviolet, followed by selection of a temperature-sensitive clone. The selected clone, Y125, showed stable temperature-sensitivity in Vero cells. Intraspinal inoculation of marmosets with the Y125 produced only minimal histopathological changes, while intracerebral inoculation of neonatal rats revealed that the Y125 did not cause hydrocephalus. Both these effects of the Y125 were similar to those of the non-neurovirulent Jeryl Lynn strain. Furthermore, subcutaneous inoculation of the Y125 induced high levels of neutralizing antibodies in all Cercopithecus monkeys examined. Although the safety and immunogenicity should be confirmed in further field trials in humans, the present results indicate that the Y125 could be a promising vaccine candidate.