Humoral Immune Response to Primary Rubella Virus Infection

Abstract

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...

Evaluation of Eight Anti-Rubella Virus Immunoglobulin G Immunoassays That Report Results in International Units per Milliliter

“…Samples that were negative by the HAI assay but had an equivocal or positive test result in one or more immunoassays were tested by Western blotting if sufficient sample remained. Western blots were performed by running rubella virus lysate on a nonreducing 10% sodium dodecyl sulfatepolyacrylamide gel, transferring the proteins to nitrocellulose, and probing for antibody in plasma samples that were diluted 1 in 100 in buffer (16,31,32).…”

Pregnant Women in and Around Dhaka City: Are Their Children at Risk of Developing Congenital Rubella Syndrome?

“…The gestational age for the three women among this RUBV specific IgM antibody positive category (Table 4) was within 12 weeks. Therefore, fetuses of these three pregnant women were at high risk of acquiring rubella infection and developing congenital rubella syndrome afterwards [15].…”

Standardization of Assays That Detect Anti-Rubella Virus IgG Antibodies

“…The humoral immune response to rubella virus infection is typical of most viral infections, with a rise in IgM followed by a slightly delayed response in specific IgG (14). Class-switching recombination allows the selection of antibody isotopes best suited to eliminating the virus.…”