scholarly journals Development and Use of an Endpoint Titration Assay To Characterize Mumps IgG Avidity following Measles, Mumps, and Rubella Vaccination and Wild-Type Mumps Infection

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Sara Mercader ◽  
Marcia McGrew ◽  
Sun B. Sowers ◽  
Nobia J. Williams ◽  
William J. Bellini ◽  
...  

ABSTRACTWaning mumps IgG antibody and incomplete IgG avidity maturation may increase susceptibility to mumps virus infection in some vaccinees. To measure mumps IgG avidity, serum specimens serially diluted to the endpoint were incubated on a commercial mumps-specific IgG enzyme immunoassay and treated with the protein denaturant diethylamine (60 mM, pH 10). End titer avidity indices (etAIs [percent ratio of detected diethylamine-resistant IgG at endpoint]) were calculated. Unpaired serum specimens (n= 108) from 15-month-old children living in a low-incidence setting were collected 1 month and 2 years after the first measles, mumps, and rubella vaccine dose (MMR1) and tested for mumps avidity. Per the receiver operating characteristic curve, the avidity assay is accurate (area under the curve, 0.994; 95% confidence interval [CI], 0.956 to 1.000), 96.5% sensitive (95% CI, 87.9 to 99.6%), and 92.2% specific (95% CI, 81.1 to 97.8%) at an etAI of 30%. When 9 sets of paired serum specimens collected 1 to 60 months post-MMR1 were tested for mumps and measles IgG avidity using comparable methods, the mumps etAI increased from 11% to 40 to 60% in 6 months. From 6 to 60 months, avidity was sustained at a mean etAI of 50% (95% CI, 46 to 54%), significantly lower (P  < 0.0001) than the mean measles etAI of 80% (95% CI, 74 to 86%). Mean etAIs in children 2 years post-MMR1 (n= 51), unvaccinated adults with distant mumps disease (n= 29), and confirmed mumps cases (n= 23) were 54, 62, and 57%, respectively. A mumps-specific endpoint avidity assay was developed and validated, and mumps avidity was determined to be generally sustained at etAIs of 40 to 60%, reaching etAIs of >80% in some individuals.IMPORTANCENumerous outbreaks of mumps have occurred in the United States among two-dose measles-mumps-rubella (MMR)-vaccinated populations since 2006. The avidity of mumps-specific IgG antibodies may affect susceptibility to mumps virus infection in some vaccinated individuals. To accurately measure mumps avidity, we developed and validated a mumps-specific IgG avidity assay that determines avidity at the endpoint titer of serially diluted serum specimens, providing results that are independent of IgG concentration. At low antibody titers, endpoint methods are considered more accurate than methods that determine avidity at a single dilution. We determined that 6 months after the first MMR dose, mumps IgG avidity is high and generally sustained at avidity indices of 40 to 60%, reaching values of >80% in some individuals. Additionally, 4% (4/103) of individuals had avidity indices of ≤30% (low avidity) 2 years after vaccination. Inadequate mumps avidity maturation may be one factor influencing susceptibility to mumps virus infection among previously vaccinated or naturally infected individuals.

2009 ◽  
Vol 58 (3) ◽  
pp. 358-364 ◽  
Author(s):  
Branko Bobić ◽  
Ivana Klun ◽  
Marija Vujanić ◽  
Aleksandra Nikolić ◽  
Vladimir Ivović ◽  
...  

Determination of the avidity of specific IgG antibodies has become a generally accepted diagnostic aid for dating Toxoplasma infection. In this study, the Labsystems, VIDAS and EUROIMMUN Toxoplasma IgG avidity assays were compared on a series of 133 Toxoplasma IgG- and IgM-positive sera from symptomatic patients (n=28), from pregnant (n=43) and non-pregnant (n=26) women, and on 18 IgG-positive and IgM-negative sera from chronically infected patients. The results showed excellent concordance between the Labsystems and VIDAS tests in both the IgM-positive (r=0.82, κ=0.771) and IgM-negative (κ=0.609) sera, whilst the agreement of the EUROIMMUN assay with both the Labsystems and VIDAS tests in the IgM-positive sera was moderate (κ=0.575 and κ=0.525, respectively) and in the IgM-negative sera was poor (κ=0.000). Analysis of the kinetics of the maturation of avidity in 13 patients in whom follow-up sera were available showed that, despite a general trend of maturation, in two patients the avidity did not become high during 6 and 11 months of follow-up. In view of the clinical setting, in the symptomatic patients, despite one case of complete discrepancy and five cases of partial discrepancy, the Labsystems and VIDAS tests were in almost perfect agreement (κ=0.812), whilst the agreement in pregnant and non-pregnant women was substantial (κ=0.754 and κ=0.708, respectively). In conclusion, the Labsystems and VIDAS tests are equally reliable for the measurement of Toxoplasma IgG avidity; the choice of test should depend on the laboratory set-up. The EUROIMMUN test may be an acceptable alternative in resource-limited settings, but should be used prudently.


2020 ◽  
Vol 44 ◽  
Author(s):  
Cyra Patel ◽  
Frank Beard ◽  
Alexandra Hendry ◽  
Helen Quinn ◽  
Aditi Dey ◽  
...  

Objective To determine population-level immunity to mumps in Australia. Methods We tested randomly selected specimens from people aged 1–49 years using the Enzygnost anti-parotitis IgG enzyme immunoassay from an opportunistically collected serum bank in 2012–2013. Weighted estimates of the proportion seropositive and equivocal for mumps-specific IgG antibody were determined by age group and compared with two previous national serosurveys conducted in 2007–2008 and 1997–1998. Results Overall, 82.1% (95% CI 80.6–83.5%) of 2,729 specimens were positive or equivocal for mumps-specific IgG antibodies (71.1% positive [95% CI 69.4–72.9%]; 10.9% equivocal [95% CI 9.8–12.2%]). The proportion positive or equivocal was higher in 2012–2013 (82.1%) than in 2007–2008 (75.5%) and 1997–1998 (72.5%), but varied by age. The proportion positive or equivocal in 2012-2013 was above 80% for all age groups older than 1 year except for 30–34 year olds, corresponding to the 1978–1982 birth cohort previously identified as most likely to have missed out on a second MMR vaccine dose. Conclusions Seropositivity to mumps in 2012–2013 was well-maintained compared with previous serosurveys. Low mumps notifications over this period in Australia suggest an absence of community-based transmission of mumps infection in the general population, but recent outbreaks among Aboriginal adolescents and young adults in close-contact settings, despite high 2-dose MMR coverage, suggest that seroprotection may be insufficient in other similar settings in Australia.


2014 ◽  
Vol 1 (3) ◽  
Author(s):  
Sigrid Gouma ◽  
Tessa M. Schurink-van't Klooster ◽  
Hester E. de Melker ◽  
Jeroen Kerkhof ◽  
Gaby P. Smits ◽  
...  

Abstract Background.  Since 2009, various mumps outbreaks have occurred in the Netherlands, affecting mostly young adults vaccinated against mumps. In this retrospective study, we estimated attack rates for symptomatic and asymptomatic mumps virus infection based on mumps-specific immunoglobulin (Ig)G concentrations in paired blood samples obtained before and after the mumps outbreaks, collected in 2 university cities. We aimed to identify a serological correlate of immune protection and risk factors for mumps virus infection. Methods.  Mumps-specific IgG levels were measured by Luminex technology in paired pre- and post-outbreak samples from students from Leiden (n = 135) and Utrecht (n = 619). Persons with a 4-fold increase in mumps IgG concentrations or mumps IgG concentrations &gt;1500 RU/mL were assumed to have had a mumps virus infection. Results.  Attack rates for symptomatic and asymptomatic mumps virus infection were 2.0% and 3.8%, respectively. Pre-outbreak mumps-specific IgG concentrations were lower among cases than among noncases (P = .005) despite vaccination history, but no serological cutoff for immune protection could be established. Mumps among housemates was significantly associated with serological evidence for mumps virus infection (odds ratio, 7.25 [95% confidence interval, 3.20–16.40]; P &lt; .001). Conclusions.  Symptomatic and asymptomatic mumps virus infections in vaccinated persons can be identified by retrospective assessment of mumps-specific IgG antibodies in blood samples.


2021 ◽  
Author(s):  
Charles Hugo MARQUETTE ◽  
Emanuela MARTINUZZI ◽  
Jonathan BENZAQUEN ◽  
Olivier GUERIN ◽  
Sylvie LEROY ◽  
...  

Background: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine. Methods: Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism. Results: In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses Conclusion: This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.


2016 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
Chowdhury Rafia Naheen ◽  
Shirin Tarafder ◽  
Humayun Sattar ◽  
Shafinaz Khan

<p>This study was undertaken to apply<em> Toxoplasma gondii</em> specific IgG avidity test in seropositive pregnant women to differentiate acute and past infection. <em>T. gondii</em> specific IgG avidity test was conducted in 39 seropositive pregnant women and their pregnancy outcomes were observed later on. Out of 39 <em>T. gondii</em> seropositive pregnant women 33 (84%) were only IgG positive and 6 (15.4%) were both IgG-IgM positive. All the IgG positive cases (100%) and 2(33.3%) IgG-IgM positive cases had high avidity antibodies and they gave birth to healthy babies. Rest of the 4 (66.7%) IgG-IgM positive women had low avidity and 50% of them had abortion and 50% gave birth to unhealthy babies. This reveals that the seropositive mothers having high IgG avidity had past infection and no risk of congenital transmission. Seropositive mothers having low IgG avidity had acute infection and so congenital transmission occurred. Presence of<em> T. gondii</em> specific IgG and IgM antibody does not indicate acute infection always. IgG-IgM positive pregnant women should be further evaluated by IgG avidity assay to confirm acute infection.</p><p> </p>


2020 ◽  
Author(s):  
Yiqi Ruben Luo ◽  
Indrani Chakraborty ◽  
Cassandra Yun ◽  
Alan H.B. Wu ◽  
Kara Lake Lynch

The kinetics of IgG avidity maturation during SARS-CoV-2 infection was studied. The IgG avidity assay used a novel label-free immunoassay technology. It was found that there was a strong correlation between IgG avidity and days since symptom onset, and peak readings were significantly higher in severe than mild disease cases.


1998 ◽  
Vol 72 (10) ◽  
pp. 8037-8042 ◽  
Author(s):  
Steven A. Rubin ◽  
Mikhail Pletnikov ◽  
Kathryn M. Carbone

ABSTRACT Prior to the adoption of widespread vaccination programs, mumps virus was the leading cause of virus-induced central nervous system (CNS) disease. Mumps virus-associated CNS complications in vaccinees continue to be reported; outside the United States, some of these complications have been attributed to vaccination with insufficiently attenuated neurovirulent vaccine strains. The development of potentially neurovirulent, live, attenuated mumps virus vaccines stems largely from the lack of an animal model that can reliably predict the neurovirulence of mumps virus vaccine candidates in humans. The lack of an effective safety test with which to measure mumps virus neurovirulence has also hindered analysis of the neuropathogenesis of mumps virus infection and the identification of molecular determinants of neurovirulence. In this report we show, for the first time, that mumps virus infection of the neonatal rat leads to developmental abnormalities in the cerebellum due to cerebellar granule cell migration defects. The incidence of the cerebellar abnormalities and other neuropathological and clinical outcomes of mumps virus infection of the neonatal rat brain demonstrated the ability of this model to distinguish neurovirulent (Kilham) from nonneurovirulent (Jeryl Lynn) mumps virus strains. Thus, this neonatal rat model may prove useful in evaluating the neurovirulence potential of new live, attenuated vaccine strains and may also be of value in elucidating the molecular basis of mumps virus neurovirulence.


2009 ◽  
Vol 16 (10) ◽  
pp. 1517-1520 ◽  
Author(s):  
V. Meroni ◽  
F. Genco ◽  
C. Tinelli ◽  
P. Lanzarini ◽  
L. Bollani ◽  
...  

ABSTRACT The aim of the study was to evaluate the influence of treatment with spiramycin on the increase of immunoglobulin G (IgG) titers and IgG avidity indexes (AI) in pregnant women with seroconversion from the beginning of therapy until delivery and after delivery. This group was compared with adult patients with recently acquired untreated toxoplasmosis. One hundred four samples from 32 pregnant women with seroconversion for toxoplasmosis and/or very low IgG AI were followed from the beginning of therapy with spiramycin until delivery. Twenty-nine women were further followed some months after delivery and interruption of therapy. Thirty-eight samples from 16 untreated, nonpregnant patients were evaluated as the control group. The Toxoplasma gondii-specific IgG antibody and the T. gondii-specific IgG AI were significantly delayed in pregnant women receiving therapy compared to nonpregnant, untreated controls, and the findings were consistent with the results of assays from two different manufacturers. The T. gondii-specific IgG AI increased in pregnant women after they gave birth. Avidity maturation is delayed during pregnancy and treatment, and low-avidity antibodies in pregnant women within 3 to 4 months cannot be taken as a sign of infection.


2021 ◽  
Author(s):  
Joseph E. Ebinger ◽  
Justyna Fert-Bober ◽  
Ignat Printsev ◽  
Min Wu ◽  
Nancy Sun ◽  
...  

AbstractIn a cohort of BNT162b2 (Pfizer–BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose.


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