Rubella-specific Antibodies Research Articles

Characterization of rubella-specific humoral immunity following two doses of MMR vaccine using proteome microarray technology.

Introduction//BackgroundThe lack of standardization of the currently used commercial anti-rubella IgG antibody assays leads to frequent misinterpretation of results for samples with low/equivocal antibody concentration. The use of alternative approaches in rubella serology could add new information leading to a fuller understanding of rubella protective immunity and neutralizing antibody response after vaccination.MethodsWe applied microarray technology to measure antibodies to all rubella virus proteins in 75 high and 75 low rubella virus-specific antibody responders after two MMR vaccine doses. These data were used in multivariate penalized logistic regression modeling of rubella-specific neutralizing antibody response after vaccination.ResultsWe measured antibodies to all rubella virus structural proteins (i.e., the glycoproteins E1 and E2 and the capsid C protein) and to the non-structural protein P150. Antibody levels to each of these proteins were: correlated with the neutralizing antibody titer (p<0.006); demonstrated differences between the high and the low antibody responder groups (p<0.008); and were components of the model associated with/predictive of vaccine-induced rubella virus-specific neutralizing antibody titers (misclassification error = 0.2).ConclusionOur study supports the use of this new technology, as well as the use of antibody profiles/patterns (rather than single antibody measures) as biomarkers of neutralizing antibody response and correlates of protective immunity in rubella virus serology.

Acute Rubella Virus Infection among Women with Spontaneous Abortion in Mwanza City, Tanzania.

Acute rubella virus infection in early pregnancy has been associated with poor pregnancy outcome ranging from spontaneous abortion, stillbirth and multiple birth defects known as Congenital Rubella Syndrome (CRS). Despite its importance the prevalence of acute rubella virus infections is not known among women with spontaneous abortion in most centres in developing countries. The present study was aimed to determine the seroprevalence of acute rubella infection among women with spontaneous abortion in Mwanza city. A total of 268 women with spontaneous abortion were enrolled from four different hospitals in Mwanza city between November 2015 and April 2016. Blood samples were collected; sera were extracted and stored at -80°C until processing. Acute rubella virus infection was diagnosed by the detection of rubella specific IgM antibodies using indirect Enzyme Linked Immunosorbent Assay (ELISA) as per manufacturer's instructions. Data were analysed by using STATA version 11. The mean age of enrolled women was 26.3±5.6 years. The prevalence of acute rubella virus infection was found to be 9/268 (3.7%, 95% CI: 1-5). Only women residing in urban areas (AOR: 5.65, 95% CI: 1.15-27.77, p=0.035) were found to predict acute rubella virus infection among cases with spontaneous abortion in Mwanza city. About four out of hundred women residing in urban areas with spontaneous abortion in Mwanza are acutely infected with rubella virus highlighting the potential of this virus in contributing to poor pregnancy outcome in this setting.

Rubella and CMV Antibodies Screening During Pregnancy - A Retrospective Study in a Tertiary Hospital

Background: In India, RUBELLA & CMV Antibodies screening is routinely carried out, but due to absence of clear intervention, its value is questionable. This retrospective study evaluated the usefulness of rubella & cmv antibody screening during pregnancy. Methods: Blood is collected from pregnant women & children, tested for rubella and CMV specific IgM Antibody by capture ELISA. The data were analysed to determine the incidence of rubella &CMV infection during pregnancy & in congenital infections. Results: In asymptomatic pregnancy females (n=252) rubella positivity was 1.58% and in woman with BOH (n=110) it was 3.66%, while CMV passivity was 2.9% in both asymptomatic and BOH women. In children (n=100) the overall positivity for rubella and CMV specific IgM antibodies was 7.5% and 12.5% respectively. The incidence of rubella and CMV infections in pregnant women & women with BOH has declined. In children, also the congenital rubella syndrome has declined but for the past 5 years the incidence of CMV infection remained same without any change. Conclusions: The incidence of rubella over the past 5 years can be reduced after giving the rubella vaccine to school going girls & women with reproductive age apart from routine vaccine. But CMV infection is a big problem due to unavailability of vaccine & safe treatment against CMV infection, so routine screening for rubella and CMV should be reserved for women with obstetric complications only.

Congenital Rubella Syndrome: A Case Report on Changes in Viral Load and Rubella Antibody Titers

To our knowledge, this is the first report of the use of real-time reverse transcription-polymerase chain reaction to assess changes in viral load in a patient with congenital rubella syndrome (CRS). Rubella-specific antibody titers were also determined. The patient was a male neonate born to a primipara with rubella infection at 10 weeks of gestation. He had no symptoms at birth, but rubella virus was detected in his pharynx, blood, and urine. His mental and physical development was normal for 1 year; however, he was diagnosed with deafness at 13 months of age. Thus, the patient was diagnosed with CRS. Rubella infection in the pharynx was almost constant until 5 months of age; however, it increased dramatically at 6 months of age. No infection was detected at 13 months. Rubella-specific immunoglobulin M titer was consistently low until 9 months of age and then decreased gradually until it became negative at 20 months of age. Rubella-specific immunoglobulin G titer was high at birth. However, it decreased at 3 months and increased again at 4 months. This titer peaked at ∼9 months and then decreased again at 13 months. This case shows that the period after the decline in maternal antibody titers, not the neonatal period, may be the most contagious period in patients with CRS.

Seroprevalence of Measles, Mumps, and Rubella Antibodies in College Students in Mumbai, India.

Measles, Mumps, and Rubella (MMR) are vaccine preventable viral infections, which cause significant mortality and morbidity globally. Increased incidence rates of these infectious diseases are observed in young adults. Information on seroprevalence data on MMR in India is limited. The objective of this study was to determine the prevalence of IgG antibodies against MMR among young adults. This was a descriptive cross-sectional study involving 192 healthy college students from Maharshi Dayanand College, Mumbai. The project was approved by the Institutional Ethics Committee of Haffkine Institute. Between December 2012 and September 2013, blood samples were collected from individuals of age 18-23 years after obtaining written informed consent from them. The quantitative determination of IgG antibodies in serum specimens against MMR was determined using enzyme linked immunosorbent assay. Data on history of vaccination were also collected from participants. Among 192 healthy college students (age 18-23 years), MMR seroprevalence was 91%, 97%, and 88%, respectively. The overall seropositivity of MMR was 79%. The highest level of seronegativity was seen with regards to rubella-specific antibodies in 12% of cases. About 96% of the participants did not know about their vaccination history while none of the participants knew about their history of MMR infections. Despite unknown vaccination status, a majority of college students in our study were found seropositive for all three infections, which indicate natural boosting. However, the proportion of seronegativity for measles and rubella was relatively higher. Especially since the study population belonged to reproductive age group, there is a concern of congenital rubella syndrome in the offspring. Although a larger multicentric study is required to confirm the findings, the results indicate that a dose of measles-rubella (MR) vaccine should be offered to these college students.

Seroprevalence of Measles , Rubella , Mumps and Varicella Specific Antibodies in Primary School Children

Seroprevalence of Measles , Rubella , Mumps and Varicella Specific Antibodies in Primary School Children

Experience of detection of rubella markers during local outbreaks in West Siberia

This paper presents an analysis of samples from 75 patients for the presence of rubella virus, viral RNA, and specific antibodies. For all samples, RNA detection was higher than virus isolation. It was found that it was not possible to isolate rubella virus in every sixth clinical sample containing the viral RNA. Primary structures of the site (from the 8072nd to 8291st nucleotide) of the rubella virus genome from 14 samples were determined. This paper shows that all the samples of rubella virus belong to the first genotype, subgroups 1h, and very likely to subgroups 1a and 1F. For the first time, the circulation of rubella virus of the genotype has been shown both prior to the start of mass vaccination in Western Siberia and after.

Post-exposure passive immunisation for preventing rubella and congenital rubella syndrome.

To assess the effectiveness of intramuscular injection or intravenous infusion of polyclonal immunoglobulins of human sera or plasma origin for preventing rubella and congenital rubella syndrome when administered to exposed susceptible people before the onset of disease.

The study of congenital cytomegalovirus, Rubella and Herpes Simplex Virus-2 infections in infants

AimsThe study was conducted to analyze the role of Cytomegalovirus (CMV), Rubella and Herpes Simplex Virus (HSV-2) as an etiological agent in congenital infections in infants. Material and methodsThe study was carried out at National Reference Centre i.e. NCDC, Delhi where samples are referred from various government hospitals of Delhi from the period of January 2013–December 2013. The samples were tested for CMV, Rubella and HSV specific IgM antibodies by μ capture ELISA (Enzyme linked Immunoassay). ResultsIn children the overall positivity of CMV, Rubella and HSV-specific IgM antibodies was 20.7%, 5.4%, and 2.3% respectively. ConclusionThe study indicated that maternal infection with CMV, Rubella and HSV-2 is a major contributory factor for congenital infections in neonates and infants and therefore screening for these viruses in early pregnancy should be made mandatory.

Seroprevalence of rubella-specific IgM and IgG antibodies among pregnant women seen in a tertiary hospital in Nigeria.

BackgroundRubella is a contagious viral infection that in pregnant women leads to the infection of a developing fetus, causing fetal death or congenital rubella syndrome.ObjectivePregnant women are not routinely screened for rubella in Nigeria. Epidemiological data on rubella is therefore necessary to create awareness and sensitize health care administrators and providers.Materials and methodsA cross-sectional study was carried out at Ahmadu Bello University Teaching Hospital between June and August 2012 to determine the prevalence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to rubella virus in pregnant women using enzyme-linked immunosorbent assay kits. Seroprevalence was compared among 160 pregnant women attending the antenatal clinic of Ahmadu Bello University Teaching Hospital and 20 nonpregnant women of childbearing age studying at Ahmadu Bello University. Prior to sample collection, questionnaires were administered to the women to obtain data on sociodemographics, awareness and knowledge of rubella, possible risk factors, and clinical symptoms associated with the viral infection.ResultsOf the 160 pregnant women, 149 (93.1%) and 62 (38.8%) were positive for anti-rubella IgM and IgG antibodies, respectively. Similarly, of the 20 nonpregnant women, 18 (90%) and eight (40%) were positive for rubella IgG and IgM antibodies, respectively. None of the possible risk factors studied were significantly associated with infection. Age and other sociodemographic factors were of little significance, and awareness of rubella was low.ConclusionThe prevalence of rubella was high in both pregnant (93.1%) and nonpregnant women (90%), suggesting sustained transmission, which further suggests endemicity. The presence of rubella IgM and IgG antibodies in pregnant women predisposes babies to congenital rubella syndrome and emphasizes the need for the initiation of a national rubella vaccination program in Nigeria.

Detection of Human parvovirus B19 (HPVB19) in serum samples from fever-rash ill individuals during the rubella outbreak (2005) in Bulgaria

The present study aimed to determine the involvement of the parvovirus B19 (HPVB19) as an etiological agent in individuals with fever-rash infections but not infected with rubella during the rubella outbreak (2005) in Bulgaria. A total of 194 serum samples with negative results for measles and rubella-specific IgM antibodies were tested in the National Reference Laboratory. The individuals aged 5–52 years (mean age 17.2 ± 10.15) were divided into four age groups: 5–14; 15–24; 25–34; and 35+ years old. Serological (indirect enzyme immunoassay – EIA) and molecular (extraction and detection of HPVB19-DNA) methods were used. A genotyping assay of the NS1-PCR product was proceeded with the MfeI restriction enzyme. Out of the total number of samples, 95 samples (48.97%) tested positive for HPVB19-IgM and 109 (56.18%) for HPVB19-DNA. The results from the genotyping assay revealed that genotype 1 (prototype B19) was dominant in 106 from 109 samples (97.25%), while genotype 3 (prototype V9) was detected in only 3 (2.75%). Subjects whose sera tested positive for IgM and had a positive PCR result formed a group that was most frequently linked (in 40% of cases) to acute infection. The highest prevalence was established in the group of the school-age children (5–14 years). The combined application of serological and molecular methods confirms the etiological role of HPVB19, and including virus genotyping, confirms the involvement of HPVB19 in the etiological palette of febrile rash diseases and provides a correct differential diagnostic approach.

Congenital Rubella Syndrome: An Overview of Clinical Presentations in Bangladeshi Children

Background: Congenital Rubella Syndrome (CRS) has long been characterized by the triad of deafness, cataract and cardiovascular malformations with or without mental retardation. Objective: This study was conducted to observe the clinical manifestations of CRS in children of Bangladesh. Materials and method: This cross sectional study was carried out in Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh and National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh. Total 40 cases of CRS were enrolled from indoor and outpatient departments of these two hospitals, who were diagnosed according to standard case definition. Serological test for rubella antibody, chest X-ray, colour Doppler echocardiography, visual examination and hearing assessment were done in relative specialised centres. Results: The mean(±SD) age of the study subjects was 6.6(±5.7) months (range: 0-24 months). Among the subjects, 68% were male and 32% were female. Serum for rubella specific antibody revealed positive IgG in 60% cases and IgM in 28% cases. Neurological problem was the most frequently observed (90%) systemic complication followed by visual problem (83%), congenital hearing loss (80%) and congenital heart disease (78%). Cataract was the commonest (55%) among visual problems and microcephaly (62%) among neurological manifestations. Patent ductus arteriosus (PDA) was the most common (37.5%) isolated structural cardiac defect. Maximum (62.5%) children came from poor socioeconomic status. Maternal onset of infection was commonly detected in 1st trimester of pregnancy. Conclusion: Diagnosis of CRS and recognition of its versatile pattern of clinical presentation are crucial for better prognosis of the affected children. DOI: http://dx.doi.org/10.3329/dmcj.v2i2.20522 Delta Med Col J. Jul 2014; 2(2): 42-47

Single-nucleotide polymorphism associations in common with immune responses to measles and rubella vaccines.

Single-nucleotide polymorphisms (SNPs) in candidate immune response genes were evaluated for associations with measles- and rubella-specific neutralizing antibodies, interferon (IFN)-γ, and interleukin (IL)-6 secretion in two separate association analyses in a cohort of healthy immunized subjects. We identified six SNP associations shared between the measles-specific and rubella-specific immune responses, specifically neutralizing antibody titers (DDX58), secreted IL-6 (IL10RB, IL12B), and secreted IFN-γ (IFNAR2, TLR4). An intronic SNP (rs669260) in the antiviral innate immune receptor gene, DDX58, was significantly associated with increased neutralizing antibody titers for both measles and rubella viral antigens post-MMR vaccination (p values 0.02 and 0.0002, respectively). Significant associations were also found between IL10RB (rs2284552; measles study p value 0.006, rubella study p value 0.00008) and IL12B (rs2546893; measles study p value 0.005, rubella study p value 0.03) gene polymorphisms and variations in both measles- and rubella virus-specific IL-6 responses. We also identified associations between individual SNPs in the IFNAR2 and TLR4 genes that were associated with IFN-γ secretion for both measles and rubella vaccine-specific immune responses. These results are the first to indicate that there are SNP associations in common across measles and rubella vaccine immune responses and that SNPs from multiple genes involved in innate and adaptive immune response regulation may contribute to the overall human antiviral response.

Mortality Associated With Pulmonary Hypertension in Congenital Rubella Syndrome

Outbreaks of rubella and congenital rubella syndrome (CRS) continue to arise in various countries where a rubella-containing vaccine is not included in the national immunization program. After a large-scale rubella outbreak in 2011, CRS cases emerged in Vietnam. The aim of this study was to clarify the clinical features of these cases with an emphasis on cardiovascular complications and outcomes. From October 2011 to September 2012, we conducted a prospective surveillance study of infants <12 months of age who had manifestations suggesting CRS at the only referral hospital in Khanh Hoa Province. These infants underwent standard examinations, echocardiography, cranial ultrasonography, automated auditory brainstem responses, blood cell count measurements, and rubella-specific antibody testing. Detected cardiovascular defects were regularly followed with echocardiography. We enrolled 38 cases of CRS characterized by a low birth weight (71%), cardiovascular defects (72%), cataracts (13%), hearing impairment (93%), purpura (84%), hepatosplenomegaly (68%), and thrombocytopenia (76%). Patent ductus arteriosus, the most common cardiovascular complication, was often associated with progressive pulmonary hypertension (PH). As of January 2013, 13 infants (34%) had died, and PH was significantly more frequent among the fatalities (P = .004); however, therapeutic closure of the ductus reversed the PH in several cases. PH-associated mortality is high among infants who have CRS in Vietnam. Providing proper assessments, continuous follow-up, and timely intervention for cardiovascular defects is critical for the management of CRS patients. Echocardiography is of diagnostic and prognostic value and can support better clinical management of CRS, even in a developing country setting.

Associations between single nucleotide polymorphisms in cellular viral receptors and attachment factor-related genes and humoral immunity to rubella vaccination.

BackgroundViral attachment and cell entry host factors are important for viral replication, pathogenesis, and the generation and sustenance of immune responses after infection and/or vaccination, and are plausible genetic regulators of vaccine-induced immunity.MethodsUsing a tag-SNP approach in candidate gene study, we assessed the role of selected cell surface receptor genes, attachment factor-related genes, along with other immune genes in the genetic control of immune response variations after live rubella vaccination in two independent study cohorts.ResultsOur analysis revealed evidence for multiple associations between genetic variants in the PVR, PVRL2, CD209/DC-SIGN, RARB, MOG, IL6 and other immune function-related genes and rubella-specific neutralizing antibodies after vaccination (meta p-value <0.05).ConclusionOur results indicate that multiple SNPs from genes involved in cell adhesion, viral attachment, and viral entry, as well as others in genes involved in signaling and/or immune response regulation, play a role in modulating humoral immune responses following live rubella vaccination.

HLA genotypes and rubella vaccine immune response: Additional evidence

Recent population-based studies have demonstrated the genetic heritability of rubella vaccine response and assessed that the HLA system may explain about 20% of the inter-individual variance in humoral immune response to this vaccine. Our earlier studies compared HLA allelic associations with rubella vaccine-specific antibodies between two smaller cohorts of healthy Rochester, MN, children (346 and 396 subjects) after two doses of rubella-containing vaccine. This study found that specific HLA alleles were consistently associated with rubella-specific antibody titers (B*27:05, DPA1*02:01, and DPB1*04:01 alleles). The current study examined HLA associations in an independent larger cohort of 1012 healthy San Diego, CA, subjects (age 19–40 years) after rubella vaccine in order to replicate our previous findings in the Rochester subjects. Two HLA associations of comparable magnitudes were consistently observed between B*27:05 (median NT50 Rochester cohort 48.9, p=0.067; San Diego cohort 54.8, p=0.047) and DPB1*04:01 (median NT50 Rochester cohort 61.6, p<0.001; San Diego cohort 70.8, p=0.084) alleles and rubella virus-neutralizing antibody titers. Additional HLA alleles resulted in consistent effects on IL-6 production in both cohorts, but did not meet criteria for statistical significance. Our data suggest these HLA alleles play a role in rubella vaccine-induced immunity and provide the basis for future studies that may explain the mechanism(s) by which these HLA polymorphisms affect immune responses to rubella vaccine.

Associations between race, sex and immune response variations to rubella vaccination in two independent cohorts

IntroductionImmune response variations after vaccination are influenced by host genetic factors and demographic variables, such as race, ethnicity and sex. The latter have not been systematically studied in regard to live rubella vaccine, but are of interest for developing next generation vaccines for diverse populations, for predicting immune responses after vaccination, and for better understanding the variables that impact immune response. MethodsWe assessed associations between demographic variables, including race, ethnicity and sex, and rubella-specific neutralizing antibody levels and secreted cytokines (IFNγ, IL-6) in two independent cohorts (1994 subjects), using linear and linear mixed models approaches, and genetically defined racial and ethnic categorizations. ResultsOur replicated findings in two independent, large, racially diverse cohorts indicate that individuals of African descent have significantly higher rubella-specific neutralizing antibody levels compared to individuals of European descent and/or Hispanic ethnicity (p<0.001). ConclusionOur study provides consistent evidence for racial/ethnic differences in humoral immune response following rubella vaccination.

Seroprevalence of rubella antibodies in The Netherlands after 32 years of high vaccination coverage

Here we present rubella virus specific antibody levels in a large cross-sectional population-based serosurveillance study performed in The Netherlands in 2006/2007.In the nationwide sample, seroprevalence was high (95%). Higher levels of rubella specific antibodies were observed in the naturally infected cohorts compared with the vaccinated cohorts. After both vaccinations, the geometric mean concentration of rubella specific antibodies remained well above the protective level. However, antibody concentrations decreased faster after one than after two vaccinations. Infants too young to be vaccinated were a risk group in the nationwide sample. In the orthodox protestant group, individuals younger than 6 years of age were at risk for an infection with rubella, consistent with a small local outbreak that recently occurred at an orthodox protestant primary school.The general Dutch population is well protected against an infection with rubella virus. However, monitoring the rubella specific seroprevalence remains an important surveillance tool to assess possible groups at risk.

High-Throughput Assay Optimization and Statistical Interpolation of Rubella-Specific Neutralizing Antibody Titers

Rubella remains a social and economic burden due to the high incidence of congenital rubella syndrome (CRS) in some countries. For this reason, an accurate and efficient high-throughput measure of antibody response to vaccination is an important tool. In order to measure rubella-specific neutralizing antibodies in a large cohort of vaccinated individuals, a high-throughput immunocolorimetric system was developed. Statistical interpolation models were applied to the resulting titers to refine quantitative estimates of neutralizing antibody titers relative to the assayed neutralizing antibody dilutions. This assay, including the statistical methods developed, can be used to assess the neutralizing humoral immune response to rubella virus and may be adaptable for assessing the response to other viral vaccines and infectious agents.

Testing of IgG and IgM against Rubella Virus in School Girls and Pregnant Women in Hanoi where an Outbreak had occurred

Background: Congenital Rubella Syndrome (CRS) is preventable illness but stays frequent in developing countries where rubella vaccination is not incorporated in national program of vaccination like in Vietnam actually. Aims: This study aimed at obtaining baseline information on acquired immunization status of school girls as well as the rate of susceptibility and rubella infection in pregnant women around a rubella outbreak in Hanoi, Vietnam. Population and methods: During and after the rubella outbreak in 2011, sera from 136 school girls (aged from 14 to 17 years) and 140 pregnant women in Hanoi French hospital were tested for rubella-specific IgG and for rubella-specific IgM (only in pregnant women) by the technique of Electro-Chemiluminescence Immunoassay (ECLIA) (Roche Diagnostics) with cut-off value ≥ 10 IU/mL for IgG and ≥ 0.3 IU/mL for IgM. Results: Rubella-specific IgG antibodies was positive in 125/136 (91.9%) school girls and 119/140 (85%) pregnant women, with strong-to-extreme concentration in 86/136 (63.2%) school girls versus 19/140 (13.6%) in pregnant women (p<0.002). Rubella-specific IgG was negative (susceptible to rubella infection) in 21/140 (15%) and rubella-specific IgM antibodies was positive in 27.9% (39/140) pregnant women, of whom 38 (27.1%) a co-existence of rubella-specific IgG and IgM were documented. Conclusions: This preliminary, baseline per/post epidemic information showed a high rate of acquired immunization in female adolescents but also high rate of susceptibility and very high rate of rubella infection in pregnant women, warranting further comprehensive studies to determine robust, nationwide epidemiological data prior to establishing the national program of immunization against rubella and identify appropriate methods for CRS surveillance in Vietnam.