Improvement in establishing the period of rubella virus primary infection using a mild protein denaturant

Condorelli, Francesca; Stivala, Aldo; Gallo, Rita; Musumeci, E.; Scatà, Maria Carmela; Strano, L.; Pennisi, Manuela; Russo, Giulia; Castro, A.; Scalia, Guido

doi:10.1016/s0166-0934(97)02215-5

Cited by 5 publications

(5 citation statements)

References 9 publications

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“…An avidity index (AI), the percentage of high-avidity antibodies in a specimen, was calculated for each specimen by dividing the absorbance at 405 nm of the urea-treated specimen by the absorbance at 405 nm of the untreated specimen and multiplying by 100. In this assay, 40% was designated as the cutoff for recent infection, with an AI higher than 40% considered as highly avid and indicative of past exposure (4,10).…”

Section: Methodsmentioning

confidence: 99%

“…Consequently, neither of these antibody isotypes could have made any significant contribution to the overall AI observed. Previous studies have also reported avidity assays to be helpful and reliable in the diagnosis of recent primary rubella virus infection (10), where IgG avidity has been found to increase with time after primary infection but not following reinfection (4,12,21). Analyzing seroconversion panels in an avidity assay probed with antibody FIG. 2.…”

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confidence: 97%

“…These diagnostic methods are subject to false-positive results due to nonspecific IgM reactivity (1,5,7,23,25,28) and false-negative results when the initial sample is obtained too late to demonstrate an increasing IgG titer (5, 9). Consequently, there has been increasing interest in the use of avidity assays to distinguish recent rubella virus infection from immune responses occurring later in the course of infection (4,10,18,22).The avidity of an antibody is a combination of the number of available binding sites and the strength (affinity) with which each individual binding site can bind the antigen. Avidity assays are generally based on commercially available enzymelinked immunosorbent assays (ELISAs) modified by the addition of a chaotropic agent (e.g., 8 M urea [18] or 100 mM diethylamine [22]) following sample application.…”

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Humoral Immune Response to Primary Rubella Virus Infection

Wilson

Camillo

Doughty

et al. 2006

Clin Vaccine Immunol

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An assay capable of distinguishing between the immune response generated by recent exposure to rubella virus and the immune response existing as a result of past exposure or immunization is required for the diagnosis of primary rubella virus infection, especially in pregnant women. Avidity assays, which are based on the premise that chaotropic agents can be used to selectively dissociate the low-avidity antibodies generated early in the course of infection, have become routinely used in an effort to accomplish this. We have thoroughly investigated the immunological basis of an avidity assay using a viral lysate-based assay and an enzyme-linked immunosorbent assay (ELISA) based on a peptide analogue of the putative immunodominant region of the E1 glycoprotein (E1 208-239 ). The relative affinities of the antibodies directed against E1 208-239 were measured by surface plasmon resonance and were found to correlate well with the avidity index calculated from the ELISA results. We found that the immune response generated during primary rubella virus infection consists of an initial low-affinity peak of immunoglobulin M (IgM) reactivity followed by transient peaks of low-avidity IgG3 and IgA reactivity. The predominant response is an IgG1 response which increases in concentration and affinity progressively over the course of infection. Incubation with the chaotropic agent used in the avidity assay abolished the detection of the early low-affinity peaks of IgM, IgA, and IgG3 reactivity while leaving the high-affinity IgG1 response relatively unaffected. The present study supported the premise that avidity assays based on appropriate antigens can be useful to confirm primary rubella virus infection.Rubella virus is a positive-sense, single-stranded RNA virus belonging to the Togaviridae family in the genus Rubivirus (17). Infection with rubella virus usually results in a mild disease that only rarely produces significant sequelae. However, primary rubella virus infection during the first trimester of pregnancy may result in the transmission of virus through the placenta and infection of the fetus. This may in turn result in congenital rubella syndrome (CRS), the most common manifestations of which are blindness, mental retardation, and deafness (15). The risk of the fetus developing CRS is 40 to 60% if infection occurs during first two months of pregnancy, 35 to 40% if it occurs in the third month of pregnancy, and 10% if it occurs in the fourth month of pregnancy (19).Rubella virus infection occurs worldwide, with a seasonal peak of infections in spring in temperate climates. Globally, only 57% of countries have rubella vaccination programs, and it is estimated that more than 100,000 cases of CRS occur each year in developing countries (27).The humoral immune response to infection commences with the production of low-affinity immunoglobulin M (IgM) molecules. Class switch recombination then results in the generation of antibody isotypes with the appropriate effector function to eliminate the invading organism. Concurre...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Humoral Immune Response to Primary Rubella Virus Infection

Wilson

Camillo

Doughty

et al. 2006

Clin Vaccine Immunol

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“…The IgG antibody avidity test has been shown to be very useful for diagnosing recent primary rubella (8,14), toxoplasmosis (21), and cytomegalovirus infection (2,27) in pregnant women; for distinguishing primary hepatitis C virus infection from chronic or past hepatitis C virus infection (18); and for serodiagnosis of many other acute viral diseases (1,13,29). Regarding measles infection, the IgG avidity test has been used for estimating the efficacy of measles vaccines (31) and for identifying secondary vaccine failures (25).…”

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

Pannuti

Morello

Moraes

et al. 2004

Clin Vaccine Immunol

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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.

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