Mumps Antibody Levels Among Students Before a Mumps Outbreak: In Search of a Correlate of Immunity

Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Atlanta, Georgia, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 09/2011; 204(9):1413-22. DOI: 10.1093/infdis/jir526
Source: PubMed


In 2006, a mumps outbreak occurred on a university campus despite ≥ 95% coverage of students with 2 doses of measles-mumps-rubella (MMR) vaccine. Using plasma samples from a blood drive held on campus before identification of mumps cases, we compared vaccine-induced preoutbreak mumps antibody levels between individuals who developed mumps (case patients) and those who did not develop mumps (nonpatients).
Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms. Antibody titers were measured by plaque reduction neutralization assay using Jeryl Lynn vaccine virus and the outbreak virus Iowa-G/USA-06 and by enzyme immunoassay (EIA).
Preoutbreak Jeryl Lynn virus neutralization titers were significantly lower among case patients than unexposed nonpatients (P = .023), and EIA results were significantly lower among case patients than exposed nonpatients (P = .007) and unexposed nonpatients (P = .009). Proportionately more case patients than exposed nonpatients had a preoutbreak anti-Jeryl Lynn titer < 31 (64% vs 27%, respectively; P = .065), an anti-Iowa-G/USA-06 titer < 8 (55% vs 14%; P = .033), and EIA index standard ratio < 1.40 (64% vs 9%; P = .002) and < 1.71 (73% vs 14%, P = .001).
Case patients generally had lower preoutbreak mumps antibody levels than nonpatients. However, titers overlapped and no cutoff points separated all mumps case patients from all nonpatients.

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Available from: Carole J Hickman, Oct 09, 2015
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    • "Compared to the rubella or the measles component the mumps vaccine confers a lower vaccine efficacy of 69–91% protection rate (Malaiyan and Menon, 2014; Lopez Hernandez et al., 2000; Harling et al., 2005; Vandermeulen et al., 2004). Flaws in vaccine-induced mumps immunity are discussed to be connected to factors like antigen drift, unreliable immune memory, waning immunity, and a lack of natural boosting due to reduced incidence of MuV (Barskey et al., 2012; Cortese et al., 2011; Latner et al., 2011). In our study, the age group between 15 to 29 years was affected in particular. "
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    ABSTRACT: From 2008 to 2013, sample sets from 534 patients displaying clinical symptoms of mumps were submitted to the German Reference Centre for Measles, Mumps and Rubella. Mumps virus infection was confirmed in 216 cases (40%) by PCR and/or serology. Confirmed cases were more frequently seen in male than in female patients (128 vs. 81); the age group predominantly affected was 15 to 29 years old (65%, median age: 26.4 years). The majority of the confirmed cases had a remote history of vaccination with one or two doses of a mumps-containing vaccine (69%). Our results indicate that mumps virus caused two outbreaks in Bavaria in 2008 and 2010/2011 and a third one in Lower Saxony in 2011. Mumps virus genotype G was preponderantly detected from 2008 to 2013. For 107 of the 216 patients with a confirmed mumps infection, we correlated the results from PCR and serology. PCR detected cases during the first week after onset of symptoms (74% positive results). PCR worked best with throat swabs and oral fluids (61% and 60% positive results, respectively). IgM was more reliable with a longer time after onset of symptoms (67%), but indirect IgM serology was of insufficient sensitivity for vaccinated mumps cases (30%); the IgM μ-capture assay detected more cases in this group. Mumps virus is able to initiate an infection in vaccinated patients (secondary vaccine failure, SVF) although it is unclear to what extent. Since SVF does occur in highly vaccinated populations and IgM will not increase to detectable levels in all SVF patients, we strongly recommend using PCR plus serology tests to avoid false-negative diagnoses in vaccinated individuals with clinical signs of mumps.
    International journal of medical microbiology: IJMM 09/2015; DOI:10.1016/j.ijmm.2015.08.011 · 3.61 Impact Factor
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    • "However, the decline could not be directly attributed to the third dose intervention. Moreover, there is no immunologic correlate of protection for mumps as there were no cutoff points for antibodies titers that separated all case patients from all non-patients [17]. It is also important to note that a decrease in antibody titer does not necessarily imply a loss of immunity, as cell-mediated immune responses and functional antibody may be protective at levels below assay detection limits [21]. "
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    ABSTRACT: Several mumps outbreaks have been reported in Europe and in the United States among highly vaccinated populations. Biological diagnosis is classically based on the detection of mumps-specific IgM, but the ability of serological tests to confirm mumps infection seems to be limited among vaccinated patients.Objectives We aim to report a mumps outbreak in an engineering school in Grenoble, France, from February to June 2013 and results of the biological testing.Study designWHO definitions were used to define cases. Mumps – specific IgM and IgG were assessed by a commercially available EIA. Mumps RNA detection by real time reverse transcriptase polymerase chain reaction tests (RT-PCR) and mumps genotyping were performed by the French National Reference Centre for Paramyxoviridae.ResultsSixty two mumps patient-cases were identified using WHO case definitions, 20 being biologically explored, of which 17 were confirmed by biological tests. Vaccination status was documented for 27 patients/62: 4 (14.8%) patients had received one dose of MMR vaccine, and 23 (85.2) two doses of MMR vaccine. Among the biologically explored patients, 83% had a positive RT PCR at the first sampling whereas only 45% had positive or equivocal IgM. All the genotyped strains were genotype G.Conclusions Mumps laboratory diagnosis in a highly vaccinated population is challenging. Serological tests among vaccinated patients should be interpreted cautiously and confirmed by RT-PCR tests at the beginning of a mumps outbreak.
    Journal of Clinical Virology 11/2014; 62. DOI:10.1016/j.jcv.2014.11.004 · 3.02 Impact Factor
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    • "The possible causes for lower than expected VE include secondary vaccine failure (waning immunity), intense exposure to high virus inoculum, and a possible mismatch between the vaccine genotype and circulating strains (1,2,18,20). However, because the level of antibodies correlating with protection remains unknown (12,21), we are unable to further elucidate the role of these factors. "
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    Emerging Infectious Diseases 04/2014; 20(4):643-8. DOI:10.3201/eid2004.131681 · 6.75 Impact Factor
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