Identification of Primary and Secondary Measles Vaccine Failures by Measurement of Immunoglobulin G Avidity in Measles Cases during the 1997 São Paulo Epidemic

Abstract

Despite almost universal use of measles vaccines in recent decades, epidemics of the disease continue to occur. Understanding the role of primary vaccine failure (failure to seroconvert after vaccination) and secondary vaccine failures (waning immunity after seroconversion) in measles epidemics is important for the evaluation of measles control programs in developing countries. After a measles epidemic in São Paulo, Brazil, 159 cases previously confirmed by detection of specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a secondary immune response, defined by an IgG avidity index of at least 30%, was established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%) had not been vaccinated and 52 (32.7%) had received one or more doses of measles vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune response, defined as an IgG avidity index of less than 30%. Among the 52 patients with documented vaccination, 25 (48.1%) showed a primary immune response and 27 (51.9%) showed a secondary immune response, thereby constituting a secondary vaccine failure. Primary vaccine failure was observed in 13 of 13 patients vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of patients receiving one or two doses after their first birthdays. These results provide evidence that measurement of IgG avidity can be used to distinguish between primary and secondary vaccine failures in vaccinated patients with measles; the method can also be a useful tool for the evaluation of measles control programs.

Neonatal Immunization with a Sindbis Virus-DNA Measles Vaccine Induces Adult-Like Neutralizing Antibodies and Cell-Mediated Immunity in the Presence of Maternal Antibodies

“…The assay was validated using a large number of positive and negative samples that were tested simultaneously for plaque reduction neutralization (PRN) and avidity. PRN titers above 200 mIU showed avidity indices above 30, similar to what has been described in human samples (26,27).…”

“…Avidity of measles serum IgG was determined using an ELISA with an urea elution step as previously described (17,26,27). Briefly, serum samples were tested for measles IgG as described in duplicate plates.…”

Characterization of Immune Responses Induced by Intramuscular Vaccination with DNA Vaccines Encoding Measles Virus Hemagglutinin and/or Fusion Proteins

“…Mice immunized with monocistronic pMSIN-FdU failed to reach the human seroprotective threshold (titer Ն 200 mIU). Avidity of measles virus antibodies has been used to estimate measles virus vaccine efficacy or vaccine failure in humans (14,35,37) and animal models (41). The presence of measles virus B-cell memory is reflected by the induction of high-avidity antibodies (i.e., with stronger antigen binding capacity).…”

“…Antibody avidity was measured by ELISA using urea as chaotropic agent to dissociate low-affinity antigen-antibody complexes. Similar assays were used to measure avidity of measles virus antibodies following vaccination or natural infection in monkeys (41) and human sera (14,15,35). Briefly, serum samples (in twofold dilutions) were incubated for 1 h at 37°C in ELISA plates coated with MV lysate as described above.…”

Impfungen / ein weiterhin ungelöstes Problem

“…[77] [99]. Bei einer Epidemie im Jahr 1997 in Brasilien, einem Land mit einer hohen Masernimpfrate, waren über 50% der Patienten sogar älter als zwanzig Jahre [100].…”