Measles virus IgG avidity assay for use in classification of measles vaccine failure in measles elimination settings.

Centers For Disease Control and Prevention, Atlanta, Georgia, USA.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.37). 09/2012; 19(11):1810-7. DOI: 10.1128/CVI.00406-12
Source: PubMed

ABSTRACT In regions where endemic measles virus has been eliminated, diagnostic assays are needed to assist in correctly classifying measles cases irrespective of vaccination status. A measles IgG avidity assay was configured using a commercially available measles-specific IgG enzyme immunoassay by modifying the protocol to include three 5-min washes with diethylamine (60 mM; pH 10.25) following serum incubation; serum was serially diluted, and the results were expressed as the end titer avidity index. Receiver operating characteristic analysis was used for evaluation and validation and to establish low (≤30%) and high (≥70%) end titer avidity thresholds. Analysis of 319 serum specimens expected to contain either high- or low-avidity antibodies according to clinical and epidemiological data indicated that the assay is highly accurate, with an area under the curve of 0.998 (95% confidence interval [CI], 0.978 to 1.000), sensitivity of 91.9% (95% CI, 83.2% to 97.0%), and specificity of 98.4% (95% CI, 91.6% to 100%). The assay is rapid (<2 h) and precise (standard deviation [SD], 4% to 7%). In 18 samples from an elimination setting outbreak, the assay identified 2 acute measles cases with low-avidity results; both were IgM-positive samples. Additionally, 11 patients (15 samples) with modified measles who were found to have high-avidity IgG results were classified as secondary vaccine failures; one sample with an intermediate-avidity result was not interpretable. In elimination settings, measles IgG avidity assays can complement existing diagnostic tools in confirming unvaccinated acute cases and, in conjunction with adequate clinical and epidemiologic investigation, aid in the classification of vaccine failure cases.

Download full-text


Available from: William Joseph Bellini, Aug 01, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Measles was eliminated in the United States through high vaccination coverage and a public health system able to rapidly respond to measles. Measles may occur among vaccinated individuals, but secondary transmission from such individuals has not been documented. Methods. Suspected cases and contacts exposed during a measles outbreak in New York City in 2011 were investigated. Medical histories and immunization records were obtained. Cases were confirmed by detection of measles-specific IgM and/or RNA. Tests for measles IgG, IgG avidity, measurement of measles neutralizing antibody titers, and genotyping were performed to characterize the cases. Results. The index case had two doses of measles-containing vaccine. Of 88 contacts, four secondary cases were confirmed that had either two doses of measles-containing vaccine or a past positive measles IgG antibody. All cases had laboratory confirmation of measles infection, clinical symptoms consistent with measles, and high avidity IgG antibody characteristic of a secondary immune response. Neutralizing antibody titers of secondary cases reached >80,000 mIU/mL 3-4 days post-rash onset while that of the index was <500 mIU/mL 9 days post-rash onset. No additional cases occurred among 231 contacts of secondary cases. Conclusions. This is the first report of measles transmission from a twice vaccinated individual. The clinical presentation and laboratory data of the index were typical of measles in a naïve individual. Secondary cases had robust anamnestic antibody responses. No tertiary cases occurred despite numerous contacts. This outbreak underscores the need for thorough epidemiologic and laboratory investigation of suspected measles cases regardless of vaccination status.
    Clinical Infectious Diseases 02/2014; DOI:10.1093/cid/ciu105 · 9.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: More severe influenza disease and poor vaccine immunogenicity is reported in HIV-infected patients. We measured antibody avidity after influenza vaccination in HIV patients to assess vaccine efficacy. Two dosing strategies (Group1: single dose, n = 28. Group2: single dose plus booster, n = 36) with an AS03A-adjuvanted H1N12009 pandemic influenza vaccine (Arepanrix, GSK) were assessed in HIV patients. Serum hemagglutination inhibition (HAI) titers and antibody avidity reported as an avidity index (AI) were measured at days 21 and 42 and at 6 months. Baseline HIV parameters were similar among all participants. Eighteen participants had measurable baseline HAI titers. In these subjects, AI was at ~9 at baseline and was not significantly increased by one or two vaccine doses. In those without detectable baseline antibodies, immunization induced modest antibody titers [Group1 HAI, 61 (26-144); Group2 HAI, 46 (28-76)] with high AI after one dose at day 21 [Group1 AI, 8.8 (7.3-10.7); Group2 AI, 8.9 (7.8-10.1)]. A second dose of vaccine generated significantly higher HAI titers at day 42 [Group1 HAI, 41 (18-90); Group2 HAI, 92 (64-132)] and persisted to 6 months [Group1 HAI, 9 (6-13); Group2 HAI, 19 (13-30)]. All subjects who produced detectable HAI titers after vaccination generated high antibody avidity (AI, 9-10), which persisted up to 6 months. In participants initially seronegative, two doses of vaccine enabled a greater percentage of subjects to respond to the vaccine and elicited higher HAI titers. All subjects who produced detectable HAI titers also rapidly generated high AI in the short and long term. We demonstrate that high avidity antibodies can be achieved after vaccination and support a two-dose immunization strategy for HIV-positive subjects.
    Journal of Clinical Immunology 05/2014; 34(6). DOI:10.1007/s10875-014-0054-z · 2.65 Impact Factor