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

Division of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland 20892, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 07/2008; 198(4):508-15. DOI: 10.1086/590115
Source: PubMed


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.

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Available from: William Joseph Bellini, Feb 28, 2015
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    • "As the recent mumps outbreaks were mainly caused by genotype G, whereas the Jeryl Lynn vaccine strain belongs to genotype A, one hypothesis could be that the recent mumps outbreaks resulted from the escape of vaccine-induced antibodies. However, WT mumps strains were effectively neutralized by vaccine-induced antibodies (Barskey et al., 2012; Carr et al., 2010; Rubin et al., 2008; Santak et al., 2012). There are also indications for a general lack of enduring humoral immunity, because mumpsspecific antibodies induced by MMR vaccination were shown to wane both in concentration and in avidity (Kontio et al., 2012). "
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    ABSTRACT: During three seasons of mumps outbreaks in the Netherlands (September 2009 - August 2012), 822 mumps cases were laboratory confirmed at the national laboratory (RIVM). Most patients were vaccinated young adults. Given the protracted endemic circulation, we studied the genetic diversity and changes of mumps virus over a period of three years. Phylogenetic analysis of the SH gene (316 bp) was performed on a representative set of 808 PCR positive specimens. Additionally, the HN gene (1749 bp) and F gene (1617 bp) were sequenced for a subset of samples (n=17). Correlations between different sequence types and epidemiological and clinical data were investigated. The outbreaks in the Netherlands were dominated by two SH gene sequence types within genotype G, termed MuVs/Delft.NLD/03.10 (variant 1) and MuVs/Scheemda.NLD/12.10 (variant 2). Sequence analysis of the HN and F genes indicated that the outbreaks were initiated by separately introduced genetic lineages. The predominance of variant 2 by the end of the first outbreak season could not be explained by any of the epidemiological factors investigated. Orchitis was more frequently reported in males infected with variant 2, irrespective of age and vaccination status. These findings illustrate genetic heterogeneity of an emerging mumps genotype and raise questions about the mechanisms driving mumps epidemiology and immunity, in relation to vaccination.
    Preview · Article · Mar 2014 · Journal of General Virology
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    • "Formerly in Spain the circulating genotype belonged to genotype H1, whereas from 2005 onwards, the circulating genotype belonged to genotype G1, as in the rest of Europe and the United States [29] [30] [31] or to the UK02-19 (a new reference strain for a new genotype)[32]. On the other hand, the vaccine genotype was effective in controlling outbreaks caused by other serotypes and so the role of genotype differences in vaccine failure, if any, is not clear [33] [34]. Besides, in countries with decade-long high immune vaccine coverage , mumps incidence declined more than 99% [8]. "
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    ABSTRACT: The aim of the study was to investigate effectiveness of mumps MMR component in communities with high MMR coverage. Outbreak-related cases of mumps born between 1995 and 2005 notified to Navarre and Catalonia public health services during the period 2005-2007 were studied. Vaccine effectiveness (VE) and their 95%CI were calculated using the screening method. Of 47 confirmed, 85.1% immunized with at least one dose (1MMR) and 44.9% with two (2MMR). Estimated VE was 85.4% (95%CI: 67.3-93.4) for 1MMR and 88.5% (95%CI: 78.1-93.9) for 2MMR. High 2MMR coverage, improved confirmation techniques and further VE studies with all confirmed cases are needed to prevent further outbreaks.
    Full-text · Article · Mar 2010 · Vaccine
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    • "All these outbreaks have been due to mumps genotype G viruses. A study from USA showed that although antibody induced by Jeryl Lynn (JL) vaccine strain effectively neutralized genotype G mumps strains, small differences in neutralization titre were observed when sera collected during an outbreak were challenged with wild type genotype G or JL strains (Rubin et al., 2008). These observations have raised public health concerns and suggested that further detailed studies on mumps vaccine efficacy and population susceptibility are warranted. "
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    ABSTRACT: Although the plaque reduction neutralization test (PRNT) is considered the "gold-standard" assay for measuring neutralizing antibodies for mumps, it is technically demanding, slow and requires large serum volumes, which limits its use for investigating mumps vaccine efficacy and population susceptibility. Therefore, an immunocolourimetric-based focus reduction neutralization test (FRNT) was developed and validated against PRNT using 30 blood donor plasma samples (16 positive, 5 equivocal, and 9 negative for mumps IgG by EIA). The samples were tested in triplicate by FRNT and PRNT in 10 and 4 separate assay runs, respectively, and 50% neutralizing antibody titres calculated using the Kärber formula. There was good correlation between the two neutralization assays (R(2)=0.88). Inter-assay variation for FRNT titres was 2-fold, compared to a 3-fold variation for PRNT titres. From the distribution of results, a positive cut-off for FRNT was defined as 1:4. In conclusion, FRNT has similar sensitivity to the PRNT and offers the advantage of speed (2 days vs. 7 days), reduced sample volume (40 microL vs. 150 microL), and the possibility of automation using 96-well plates. FRNT appears to be a good substitute for PRNT for characterising the immune response to mumps and for vaccine efficacy studies.
    Full-text · Article · Sep 2009 · Journal of virological methods
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