Evaluation of the Bio-Rad BioPlex Measles, Mumps, Rubella, and Varicella-Zoster Virus IgG Multiplex Bead Immunoassay

Abstract

The goal of this study was to compare the BioPlex 2200 measles, mumps, rubella, and varicella-zoster virus (MMRV) IgG multiplex assays (Bio-Rad Laboratories, Hercules, CA) to routine testing by enzyme immunoassay (EIA). Serum specimens (n ‫؍‬ 500) submitted to our reference laboratory for routine MMRV IgG testing by EIA were also tested by the BioPlex assays. Following testing, the BioPlex measles, mumps, rubella, and varicella-zoster virus assays demonstrated agreements of 91.6% (95% confidence interval [CI], 88.8% to 93.7%), 94.2% (95% CI, 91.7% to 95.7%), 94.4% (95% CI, 92.0% to 96.1%), and 91.8% (95% CI, 89.0% to 93.9%), respectively, compared to the results of EIA. Timing studies showed that the BioPlex MMRV assay could provide complete analysis of 100 serum specimens in 1.7 h, compared to 5.5 h by EIA. These data indicate that the BioPlex MMRV IgG assays exhibit comparable performance (93% overall agreement [1,860/2,000 results];‫؍‬ 0.67) to routine testing by EIA. The BioPlex assays allow for the simultaneous detection of all four analytes, thereby eliminating potential aliquot errors and reducing turnaround time.The incidence of disease caused by measles, mumps, rubella, and varicella-zoster virus (MMRV) has been significantly reduced in developed countries due to the implementation of effective immunization programs (1, 6). However, outbreaks of disease continue to occur in the United States and worldwide due to vaccine failure, declining immunization rates, and waning immunity (2, 3, 5).Laboratory testing for IgG class antibodies to MMRV plays an important role in the management of patients and health care workers. For example, testing for IgG class antibodies to rubella virus is routinely performed during the prenatal period (7), and detection of rubella IgG during the first trimester indicates that the mother is protected from primary infection. Furthermore, immunocompromised hosts (e.g., transplant recipients) are commonly screened for immunity to varicella, which may cause devastating disease in the immunosuppressed population if a primary infection occurs (8).Until recently, most clinical laboratories have used methods such as indirect immunofluorescence (IFA), enzyme immunoassay (EIA), and enzyme-linked fluorescence assay (ELFA) for the detection of IgG class antibodies to MMRV. These methods have demonstrated reliable performance; however, they are labor-intensive, time-consuming, and, in the case of IFA, subjective. In addition, these conventional methods require four separate assays to test for IgG class antibodies to MMRV, thereby increasing sample volume requirements as well as hands-on time. These limitations have led to the recent development of multiplex flow immunoassay (MFI) technology, which allows for multiple analytes (e.g., antibodies) to be detected in a single reaction.The Bio-Rad BioPlex MMRV IgG assays (Bio-Rad Laboratories, Hercules, CA) recently received FDA approval for the simultaneous detection of IgG class antibodies to MMRV in human serum or EDTA/heparinized plasma sample...

Varicella seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection

“…Serum specimens for all subjects were processed with the BioRad BioPlex 2200 MMRV IgG multiplex flow immunoassay, which has a sensitivity of 92.2% and specificity of 100% for the varicella component when compared to traditional testing via enzyme immunoassay [23], and overall agreement of 96% when compared to anticomplement immunofluorescence tests [24]. Subjects with negative titers received two varicella vaccine doses in accordance with standard immunization practices.…”

Calibration and Evaluation of Quantitative Antibody Titers for Measles Virus by Using the BioPlex 2200

“…In this study, the correlation of the quantitative result of the BioPlex 2200 MMRV IgG assay and the reference method (PRNT) is higher for "nonequivocal" specimens (Ͼ192 mIU/ml) and specimens with low concentrations of neutralizing antibody do not correlate well. This observation has been previously reported for other EIA methods and is attributed to the fact that PRNT only measures neutralizing IgG, whereas EIA-based tests measure total anti-measles IgG (14,15,20,26,29). This lack of sensitivity may lead to an underestimation of the number of protected individuals in seroepidemiological studies.…”

“…Specimens tested on the platform are reported as positive (immune), equivocal, or negative (nonimmune). Previous work has shown that the qualitative results produced by this commercially available assay correlate well with existing EIA methods (20). Because the BioPlex 2200 MMRV IgG assay generates a quantifiable value (relative fluorescence intensity [RFI]), it is possible that this assay can be used as a quantitative method, which is off-label from the commercial product.…”

“…The BioPlex 2200 MMRV IgG assay has the potential to simplify the screening of large numbers of specimens. It has a higher throughput and reduced turnaround time compared to automated conventional plate-based EIA (20). By combining both a high-throughput screening assay and the PRNT reference method, one can maximize the efficiency for screening while maintaining accuracy in specimens with low levels of antibodies.…”

Microbiology laboratory and the management of mother-child varicella-zoster virus infection

“…However, some of the international guidelines, while stressing the importance of this value, point out that this cut-off value may vary depending on vaccinations, ethnicity or age [54] . Microarrays: Finally, there are also some serological microarray tests for the simultaneous screening of antibodies against VZV and viruses such as herpes simplex virus (HSV-1 and HSV-2), cytomegalovirus, mumps, rubella or measles [415][416][417][418][419] .…”