4.6 Determination of measles- or rubella-specific IgG avidity

Antibody avidity refers to the net strength of the interaction of a multivalent immunoglobulin molecule with antigen. Depending upon the strength of this binding, the complex formed may or may not be easily dissociated. Avidity assays measure the antigen-binding avidity of IgG antibodies by incorporating a mild protein denaturant to distinguish low avidity antibodies produced at an early stage of a primary infection from those with high avidity.

Low avidity IgG is usually present in a current infection, but the avidity can remain low for up to 3 months after rash onset. Because avidity testing requires that detectable virus-specific IgG is present, avidity testing may require a second serum if the initial serum was collected within a few days after rash onset. Demonstration of low avidity IgG provides the additional laboratory evidence to support a positive IgM result from a suspected measles or rubella case that may be considered as a potentially nonspecific (‘false positive’) result. High avidity IgG is consistent with an infection in the past or a previous vaccination (>3 months prior to blood collection). A confirmed measles case with a history of vaccination and high avidity IgG is consistent with a measles reinfection case (see section 4.7).

Modifications of commercial EIA IgG assays are utilized for avidity assays that are developed in-house but these avidity assays are difficult to establish and require a range of avidity controls that must be validated. The controls must be included in each run so having a substantial volume of well-characterized validity controls is essential. There are commercial kits for determination of rubella avidity, but they may have limited distribution.