Sex: U
Vaccine: MMR
Symptoms: Vaccination failure
Clinical narrative: Information has been received from a published literature article, concerning a measles IgG avidity assay for use in classification of measles vaccine failure in measles elimination settings. Traditionally, measles IgG avidity assays have been used to classify primary (PVF) and secondary (SVF) vaccine failures. PVF are vaccinated individuals who never responded to the vaccine and present with classic measles upon measles virus infection. In serum collected within 4 weeks of rash onset, measles IgM is present and measles IgG is of low avidity. Low-avidity results classify PVF and help confirm suspect cases even with a record of prior vaccination. In contrast, SVF are individuals with documented IgG antibody responses to vaccination whose antibody has waned over time, making them susceptible to measles virus infection. SVF produce high-avidity antibodies upon challenging with measles virus. High-avidity results classify SVF and can be used to verify secondary immune responses in modified-measles cases with elevated plaque reduction neutralization (PRN) titers (> 30,000 mIU/ml), a newly proposed biomaker to confirm SVF that otherwise would not be confirmed by routine serology or molecular-based tests. A well-validated measles avidity assay is needed for use as a complement to IgM testing in the serological confirmation of clinical ambiguous cases and to aid in the classification of measles vaccine failures. This study describes the development, evaluation, and applicability of a measles avidity assay. A commercially available measles IgG enzyme immunoassay was adapted for wider use. This case concerns 47 cases of vaccine failure, including 2 PVF cases, 16 SVF cases, and 29 possible SVF cases. Samples from healthy adults exposed to measles virus infection or vaccination more than a year before collection were assumed to have high-avidity antibodies. Samples collected within 3 months after measles rash onset or first-time vaccination from IgM-positive children aged 9 months and older (to avoid maternal antibody interference) were expected to have results showing low- and intermediate-avidity antibodies, depending on the timing of sample collection. IgM was detected using the CDC measles capture IgM enzyme immunoassay. A total of 319 serum samples were retrospectively gathered from specimen collections acquired from diverse locations in the years 1988 to 2004 and archived at the authors institution. Institutional review board approval was obtained for outbreak and vaccine study samples. Specimens were also obtained from blood donated by healthy individuals under a CDC Institutional Review Board-approved protocol and from individuals involved in outbreaks who previously had natural measles or had received at least one dose of measles vaccine. The samples were distributed into group A and group B. Assumptions made for samples with uncertain epidemiological information (group B). Avidity results for 99 group B samples for which assumptions were made classified 32 acute infections, 2 PVF cases, 16 SVF cases, and 29 possible SVF cases, while results from 20 samples could not be interpreted. In conclusion, this paper introduces a new measles avidity assay that is ready to be used in elimination settings. It is highly accurate, precise, and reproducible, as well as sensitive and specific. The assay is able to detect measles-specific antibody maturation over time, in line with previous observations. Besides vaccine failure classification, avidity testing can provide very valuable information in confirming those cases with RT-PCR-negative results or with questionable IgM results. It must be emphasized that the assay can only be used to help rule in measles cases, but not to rule them out. With appropriate assay evaluation, it may be possible to adapt other commercially available measles IgG platforms to avidity testing by using the DEA elution method presented here. This avidity method worked well with another commercial plate coated with whole measles virus antigen (data not shown). Finally, the endpoint titration method was used because it is independent of the IgG concentration and it is considered superior to the single-dilution method. However, in situations where time or resources are limited, the avidity assay could be performed using a single dilution. This is one of several reports received from the same source (linked with 1212USA000592). Additional information has been requested.