The best-known mechanism of action of antibody-mediated virus neutralization is to impede the entrance of viruses to host cells, as determined by neutralization assays. Antibodies may also inhibit the exit of rubella virus (RV) from infected host cells; in this case, the interaction of the antibodies with their domains must occur on the plasma membrane, because antibodies cannot enter the cells. In the present study, we were able to block temporally the exit of virions from RV-infected cells by the binding of monoclonal antibody (mAb) H3 to their surface. The objective was accomplished in three steps: first, we determined the duration of the viral replication cycle; then we established the kinetics of the presence of the domains defined by our mAbs in the cytoplasm of RV-infected VERO cells; and, finally, we assessed the release of viral particles to the supernatant of infected VERO cells in the presence or absence of mAbs or positive and negative mice sera. RV-specific mice sera and mAb H3, which binds to the amino acid sequence 208-239 of the RV-E1 glycoprotein, were able to delay for 24 hours the release of virions from infected cultures, suggesting that the reaction of mAb H3 with its epitope may arrest any change necessary for the assembly and/or release of virions. In conclusion, the neutralizing domain recognized by mAb induces antibodies that can block the viral replication by several mechanisms of action, such as the obstruction of virus entry into cells and the delay of viral release. All of these mechanisms are intimately involved in the critical virus-host cell interactions that allow self-limitation of the infection.
To date, human adenoviruses are classified into 53 types (types 1-51 and types 53 and 54), which have been grouped into six species named A through F, and the recently identified type 52 has been proposed as member of a new species, G. Type classification is based on type-specific epitopes within loop 1 (L1) and loop 2 (L2) of the hexon protein, which contain seven hypervariable regions that are responsible for type specificity. In this paper, we present the characterization of an adenovirus strain isolated from a male AIDS patient in Cordoba, Argentina. This strain was found to be a member of species D by genomic Sma I restriction analysis. Sequencing of the L1 and L2 regions of the hexon gene and immunological characterization by virus neutralization revealed this hexon to be unique and distinct from the previously identified hexons of types within species D. A seroepidemiologic study in the human population of Cordoba showed that this strain was not endemic in the local human population.
The protective immune responses against rubella virus (RV) are related to its neutralizing epitopes, an issue that is important to consider when assessing the immune status of patients with remote infection. In the present paper, we compare the antibodies detected by a synthetic-peptide-based enzyme immunoassay (EIA) with antibodies detected by the traditional technique of hemagglutination inhibition (HIA) in patients with remote RV infection. The synthetic peptide used as an antigen (SP15) represents a neutralizing epitope that corresponds to amino acids 208 to 239 of the E1 glycoprotein. The SP15-EIA was developed, all variables that affected the assay were standardized, and the test was validated using reference sera. Serum samples (n ؍ 129) from patients with remote RV infection were tested by HIA and SP15-EIA. Discrepant sera were assayed by MEIA (IMX/Abbot). The comparison between HIA and SP15-EIA, taking HIA as the standard methodology for determining immune status, showed that SP15-EIA is very specific and sensitive for detecting protecting antibodies (specificity, 100%; sensitivity, 98.20%). This study demonstrates that antibodies against the neutralizing domain represented by SP15 would be important in the memory response after natural infection and may be a good tool in the determination of the true immune status of patients with remote infection with regard to RV. Rubella virus (RV) is the etiologic agent of German measlesand is the sole member of the genus Rubivirus in the Togaviridae family. During the first trimester of pregnancy, the infection may induce congenital malformations and viral persistence in the human fetus (26).The RV virion contains an RNA genome enclosed in an icosahedral capsid composed of protein C (33 kDa). Surrounding this nucleocapsid is a lipid bilayer, in which viral glycoproteins E1 (58 kDa) and E2 (42 to 47 kDa) are embedded (18). The humoral immune response to RV is predominantly to the E1 glycoprotein and persists indefinitely after infection (13,17).The E1 glycoprotein has been suggested to be the immunodominant antigen, since most virus-neutralizing antibodies are directed against this subunit. Monoclonal antibodies (MAbs) were used to define the neutralizing domains on the E1 glycoprotein whose amino acid sequences were determined by overlapping synthetic peptides (9,11,12,14,21,22,24). One of these domains was defined by three independent MAbs that recognized the same sequence, represented by the synthetic peptide SP15 (E1 amino acids 208 to 239) (4, 25). Moreover, SP15 was shown to induce polyvalent antibodies with neutralizing and hemagglutination inhibition activity in mice and rabbits. The sequence of SP15 is present in several strains of RV, such as Therien, Judith, M33, HPV77, RA27/3, Gilchrist, wildtype Cordoba, and Kara 95 (5, 25).Other authors using a similar synthetic peptide, BCH-178C (E1 amino acids 213 to 239), showed the existence of human antibodies that recognize this domain (15,16,27). These authors indicate that BCH-178C can favorably replace curr...
Little is known about long-lasting measles protective immunity when exposure to wild-type or vaccine measles virus precedes HIV infection. The results obtained suggest that measles immunity wanes and the lowest measles geometric mean titres (GMT) were significantly associated with measles vaccine-induced immunity in individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml) compared to naturally induced immunity in HIV-infected adults (100% prevalence, GMT 340 mIU/ml, P = 0·0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P = 0·0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347 mIU/ml, P = 0·017). The study was conducted in an area without wild-type virus circulation since 2000. The absence of virus circulating may alter the paradigm of lifelong immunity to measles virus after vaccination. As the proportion of HIV-infected individuals possessing only vaccine-induced immunity continues to grow, checking the status of measles immunity in this group is strongly recommended.
There is, apparently, only one serological type of rubella virus (RV) in the population, although several isolates exist with different characteristics. Some authors failed to detect significant differences among RV strains by neutralization, hemagglutination inhibition, and enzyme immunoassay using polyclonal and monoclonal antibodies, but differences in growth, plaque morphology, and temperature sensitivity between vaccine and wild-type strains were shown by Chantler et al. (3) With the purpose of analyzing the possible differences among several strains of RV, we studied the affinity constant of two monoclonal antibodies (MAbs) for two conserved neutralizing epitopes. Wild-type Cordoba (regional isolation of a post-natal infection) and RA 27/3 (vaccine) strains of RV were tested. H3 and H14 MAbs were generated against wild-type Cordoba strain. They defined two epitopes with conserved neutralizing and hemagglutinating activity on both strains. The affinity of the MAbs (expressed as the affinity constant), was greater for Cordoba strain than for RA 27/3. Analyzing the results obtained, we conclude that the neutralizing epitopes defined by our MAbs on E1 glycoprotein are conserved in the two strains, but react with significative different affinities. This could be a way to characterize antigenically different viral strains of the same serotype.
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