scholarly journals Serum Neutralizing Activity against B.1.1.7, B.1.351, and P.1 SARS-CoV-2 Variants of Concern in Hospitalized COVID-19 Patients

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1347
Author(s):  
Claudia Maria Trombetta ◽  
Serena Marchi ◽  
Simonetta Viviani ◽  
Alessandro Manenti ◽  
Linda Benincasa ◽  
...  

The recent spreading of new SARS-CoV-2 variants, carrying several mutations in the spike protein, could impact immune protection elicited by natural infection or conferred by vaccination. In this study, we evaluated the neutralizing activity against the viral variants that emerged in the United Kingdom (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) in human serum samples from hospitalized patients infected by SARS-CoV-2 during the first pandemic wave in Italy in 2020. Of the patients studied, 59.5% showed a decrease (≥2 fold) in neutralizing antibody titer against B.1.1.7, 83.3% against P.1, and 90.5% against B.1.351 with respect to the original strain. The reduction in antibody titers against all analyzed variants, and in particular P.1 and B.1.351, suggests that previous symptomatic infection might be not fully protective against exposure to SARS-CoV-2 variants carrying a set of relevant spike mutations.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hitoshi Kawasuji ◽  
Yoshitomo Morinaga ◽  
Hideki Tani ◽  
Miyuki Kimura ◽  
Hiroshi Yamada ◽  
...  

AbstractAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.


PEDIATRICS ◽  
1967 ◽  
Vol 39 (2) ◽  
pp. 202-213
Author(s):  
Jean F. Kenny ◽  
Mary I. Boesman ◽  
Richard H. Michaels

Stools of newborn breast-fed infants may contain significant amounts of hemagglutinating antibody to enteropathogenic E. coli and neutralizing antibody to polioviruses. Stool titers averaged only fourfold lower than maternal milk titers for antibacterial and less than twofold lower for antiviral activity. Similar ratios of stool:milk activity were also found for paired specimens obtained during the second and third postpartum months. The stool antibodies were stable at 56°C and exhibited definite specificity. Bacterial hemagglutinins in feces were more sensitive to mercaptoethanol than the poliovirus neutralizing activity. Stools from breast-fed infants contained gamma-1 globulins similar to those in milk, including IgA and small amounts of IgM. Meconium from bottle-fed infants with high serum antibody titers to polioviruses contained traces of homotypic neutralizing antibody. Antiviral and antibacterial activity were not detected in transitional and later stools from artificially fed infants, nor were human immune globulins. Milk bacterial hemagglutinating antibodies were more resistant to acid and to pepsin than those in serum. Furthermore, acid had a less deleterious effect on virus neutralizing activity in milk than it had on that in serum, and it also had less effect on the milk antiviral than on the milk antibacterial antibodies.


2021 ◽  
Author(s):  
Koen B. Pouwels ◽  
Emma Pritchard ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
David W. Eyre ◽  
...  

AbstractThe effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior infection and in younger adults. With B.1.617.2, infections occurring after two vaccinations had similar peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2.


1976 ◽  
Vol 4 (5) ◽  
pp. 437-442
Author(s):  
G Gerna ◽  
R W Chambers

A new plaque assay for the quantitation of varicella-zoster virus and a plaque reduction neutralization test for the determination of neutralizing antibody titer have been developed using the indirect immunoperoxidase technique. As compared with the classical plaque assay using a solid overlay, the test gives earlier results since plaque counting can be performed on day 3 after the inoculation of cell cultures. In six patients with zoster infection, neutralizing antibody titers ranged from 1:20 to 1:40 before the onset of infection and reached high levels (1:320 to 1:5,120) during the convalescent phase of the disease. Complement-fixing (CF) titers were all negative (less than 1:8) in prezoster serum samples from the same patients and ranged from 1:128 to 1:2,048 in the convalescent-phase sera. In the two cases in which late serum samples were available, neutralizing antibody titers matched the preillness levels, whereas CF titers dropped to undetectable levels. Neither neutralizing nor CF antibody was detected in two sera from individuals with no history of varicella-zoster infection. No differences in virus titers or neutralizing antibody titers were observed between the immunoperoxidase and the classical plaque assays. The appropriate characterization of reagent specificity is required before routine application of the test.


2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S32-S32
Author(s):  
Y R Luo ◽  
C Yun ◽  
A H Wu ◽  
K L Lynch ◽  
I Chakraborty

Abstract Introduction/Objective Since the start of the COVID-19 pandemic, much research has focused on the kinetics and magnitude of humoral immune response. With the advantages of monitoring real-time immunoreactions, label-free immunoassay (LFIA) is becoming a powerful tool in serology studies. We have developed LFIAs to measure SARS- CoV-2 antibody avidity and neutralization activity in a cohort of COVID-19 patients and determine if they correlate with antibody concentration. Serial serum samples collected from mild to severe COVID-19 patients were measured out to 8 months post-symptom onset to determine the durability of the neutralizing antibody response. Methods/Case Report Based on thin-film interferometry technology, we established a label-free IgG avidity assay and a label-free surrogate virus neutralization test (LF-sVNT). For measurement, sensing probes pre-coated with receptor-binding domain (RBD) of SARS-CoV-2 spike protein are applied to serum samples containing SARS-CoV-2 antibodies. The label-free IgG avidity assay measures the binding strength between RBD and IgG under urea dissociation. The LF-sVNT analyzes the binding ability of RBD to ACE2 after neutralizing RBD with antibodies. Results (if a Case Study enter NA) IgG avidity indices and neutralizing antibody titers (IC50) were determined from serum samples (n=246) from COVID-19 patients (n=113). IgG concentrations were measured using a fluorescent immunoassay. The neutralizing antibody titers showed a weak correlation with IgG concentrations and no correlation with IgG avidity indices. Over the time course up to 8 months post-symptom onset, IgG concentrations and neutralizing antibody titers presented similar trends: an initial rise, plateau and then in some cases a gradual decline after 40 days. The IgG avidity indices, in the same cases, plateaued after the initial rise. Conclusion The results demonstrated that LFIA could be used an excellent solution in the determination of SARS- CoV-2 antibody characteristics. The study found that IgG concentration and neutralizing antibody titer declined over time, while IgG avidity index remained constant after reaching a plateau. The decline of antibody neutralization activity can be attributed to the reduction in antibody quantity rather than the deterioration of antibody quality, as measured by antibody avidity.


2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  

The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.


2019 ◽  
Vol 31 (4) ◽  
pp. 288-295 ◽  
Author(s):  
Adrienne Guignard ◽  
François Haguinet ◽  
Stéphanie Wéry ◽  
Phirangkul Kerdpanich

Understanding maternal dengue virus (DENV) neutralizing antibody kinetics in infants remains timely to develop a safe and effective childhood immunization. This retrospective study evaluated the prevalence and persistence of maternal antibody titers against DENV serotypes 1 to 4 in 139 Thai infants at 2, 6, and 7 months of age, using serum samples collected in a vaccination trial ( http://clinicaltrials.gov ; NCT00197275). Neutralizing antibodies against all 4 DENV serotypes were detected in 87.8% and 22.9% of infants at 2 and 7 months, respectively. At 2 months, DENV-4 neutralizing antibody geometric mean titers were notably lower (80) compared with DENV-1 to DENV-3 (277-471). Our results corroborate previous findings that DENV-1 to DENV-4 maternal antibodies persist at 7 months despite titers decrease from 2 months onwards. As persisting maternal antibodies may inhibit immune responses in DENV-vaccinated infants, a comprehensive understanding of DENV antibody kinetics is required in the perspective of vaccine development for infants.


Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 66 ◽  
Author(s):  
Gabriele Anichini ◽  
Claudia Gandolfo ◽  
Simonetta Fabrizi ◽  
Giovan Battista Miceli ◽  
Chiara Terrosi ◽  
...  

An increase in measles cases worldwide, with outbreaks, has been registered in the last few years, despite the availability of a safe and highly efficacious vaccine. In addition to an inadequate vaccination coverage, even in high-income European countries studies proved that some vaccinated people were also found seronegative years after vaccination, thus increasing the number of people susceptible to measles infection. In this study, we evaluated the immunization status and the seroprevalence of measles antibodies among 1092 healthy adults, either vaccinated or naturally infected, in order to investigate the persistence of anti-measles IgG. Among subjects who received two doses of measles vaccine, the neutralizing antibody titer tended to decline over time. In addition, data collected from a neutralization assay performed on 110 healthy vaccinated subjects suggested an inverse correlation between neutralizing antibody titers and the time elapsed between the two vaccinations, with a significant decline in the neutralizing titer when the interval between the two doses was ≥11 years. On the basis of these results, monitoring the serological status of the population 10–12 years after vaccination could be important both to limit the number of people who are potentially susceptible to measles, despite the high efficacy of MMR vaccine, and to recommend a booster vaccine for the seronegatives.


2020 ◽  
Vol 222 (10) ◽  
pp. 1620-1628 ◽  
Author(s):  
Steven B Bradfute ◽  
Ivy Hurwitz ◽  
Alexandra V Yingling ◽  
Chunyan Ye ◽  
Qiuying Cheng ◽  
...  

Abstract Background Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway. Methods We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Results NAb titers in the donor CP units were low (<1:40 to 1:160) and had no effect on recipient neutralizing activity 1 day after transfusion. NAb titers were detected in 6 of 12 patients on enrollment and in 11 of 12 at ≥2 time points. Average titers peaked on day 7 and declined toward day 14 (P = .004). Nab titers and immunoglobulin G levels were correlated in donor plasma units (ρ = 0.938; P < .001) and in the cumulative patient measures (ρ = 0.781; P < .001). Conclusions CP infusion did not alter recipient NAb titers. Prescreening of CP may be necessary for selecting donors with high titers of neutralizing activity for infusion into patients with COVID-19. Clinical Trials Registration NCT04434131.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2270
Author(s):  
Gloria Griffante ◽  
Shikha Chandel ◽  
Daniela Ferrante ◽  
Valeria Caneparo ◽  
Daniela Capello ◽  
...  

Longitudinal mapping of antibody-based SARS-CoV-2 immunity is critical for public health control of the pandemic and vaccine development. We performed a longitudinal analysis of the antibody-based immune response in a cohort of 100 COVID-19 individuals who were infected during the first wave of infection in northern Italy. The SARS-CoV-2 humoral response was tested using the COVID-SeroIndex, Kantaro Quantitative SARS-CoV-2 IgG Antibody RUO Kit (R&D Systems, Bio-Techne, Minneapolis, USA) and pseudotype-based neutralizing antibody assay. Using sequential serum samples collected from 100 COVID-19 recovered individuals from northern Italy—mostly with mild disease—at 2 and 10 months after their first positive PCR test, we show that 93% of them seroconverted at 2 months, with a geometric mean (GeoMean) half-maximal neutralization titer (NT50) of 387.9. Among the 35 unvaccinated subjects retested at 10 months, 7 resulted seronegative, with an 80% drop in seropositivity, while 28 showed decreased anti-receptor binding domain (RBD) and anti-spike (S) IgG titers, with a GeoMean NT50 neutralization titer dropping to 163.5. As an NT50 > 100 is known to confer protection from SARS-CoV-2 re-infection, our data show that the neutralizing activity elicited by the natural infection has lasted for at least 10 months in a large fraction of subjects.


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