Assessment of mumps virus-specific antibodies by different serological assays: which test correlates best with mumps immunity?

Abstract

Mumps is one of the vaccine-preventable childhood diseases and it has not yet been eradicated in Germany. This raises the question as to whether the available mumps vaccines are effective enough to prevent mumps and which antibody test system allows the authentic assigning of mumps-specific immunity. In an attempt to answer this question, we analysed 227 sera samples from medical students of the University Hospital Frankfurt/Main, Germany, using different test systems: indirect immune fluorescence, neutralisation assay, routine ELISA and newly developed immunoassays, which contain the mumps nucleoprotein and the wild-type strain Enders ATCC VR106, respectively. Mumps vaccination coverage of the screened collective amounted to 75.1%, which differs notably from the detected mumps-specific seropositivity rates in the literature (range 53.3% to 82.4%). In contrast, a small group of unvaccinated students had much higher seropositivity rates. Of course, assigned vaccination coverage and calculated seropositivity rates are not effective enough to interrupt the transmission of the mumps virus. The often-occurring mumps outbreaks, some in highly vaccinated populations, may not always demonstrate vaccine failure. The investigation of newly developed test systems and the occurrence of different mumps virus genotypes should also be considered.

Estimates of Mumps Seroprevalence May Be Influenced by Antibody Specificity and Serologic Method

“…Although neutralizing antibody is thought to be essential for protection (40) and PRN titration is generally considered to be the gold standard for mumps serology, previous attempts to determine a reliable threshold for protective PRN titers have been unsuccessful (20). To add further ambiguity, there have been several reports of poor correlations between mumps PRN titration and various other serologic methods, such as ELISA and immunofluorescent assays (IFA) (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). These studies indicated that mumps serologic data must be interpreted with caution.…”

“…Several reports have indicated that mumps-neutralizing antibody does not correlate particularly well with mumps IgG ELISA measurements (25)(26)(27)(28)(29)(30)(31)(32)(33). An explanation for these observations is that mumps antibodies predominantly measured by ELISAs which use whole-virus antigen differ from those measured by plaque neutralization tests.…”

“…As a result, it has been widely replaced by the faster and more convenient ELISA. Interestingly, however, numerous reports (25)(26)(27)(28)(29)(30)(31)(32)(33)(34) indicate that the correlations between mumps PRN titers and IgG ELISAs, which use whole virus as the target antigen, range from poor (32) to significant but imperfect (31). Here, we report the development of mumps NP-and HN-specific ELISA methods that facilitate the analysis of sera with higher degrees of resolution than whole-virus ELISA methods.…”

Antigenic differences between vaccine and circulating wild-type mumps viruses decreases neutralization capacity of vaccine-induced antibodies

“…Since the correlation of serological test results and clinical protection is particularly poor in mumps vaccination [11,25,26], two types of tests were used in this study : the HI test and the plaque reduction neutralization test (PRNT). Genotyping based on the SH (presented above), although informative, cannot lead to a conclusion on the cross-reactive potential between different mumps viruses.…”

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population

“…However, no correlation could be found between mumps seroprevalence and the likelihood of outbreaks. Several studies have brought into question whether measuring antibody levels following vaccination is an effective method of assessing resistance to vaccine-preventable viral infections (12,20), against which a cell-mediated immunity response appears to provide protection in addition to humoral immunity (14,21). It should be noted, however, that there does seem to be some correlation between levels of humoral antibody and the ability to resist infection (13).…”