scholarly journals A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron

2021 ◽  
Author(s):  
Kang Wang ◽  
Zijing Jia ◽  
Linlin Bao ◽  
Lei Wang ◽  
Lei Cao ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Human Monoclonal Antibodies ◽  
Atomic Structures ◽  
Local Conformation ◽  
Binding Interface ◽  
Major Class ◽  
Ancestral Virus ◽  
The Right ◽  
Neutralization Antibody Titer

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine.

scholarly journals Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients

2021 ◽  
Author(s):  
Lu Lu ◽  
Bobo Mok ◽  
Linlei Chen ◽  
Jacky Chan ◽  
Owen Tsang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
World Health ◽  
Whole Genome Sequence ◽  
Live Virus ◽  
Significant Difference ◽  
Antibody Titers ◽  
Ancestral Virus ◽  
Health Organization

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike protein mutations which have been found to evade neutralizing antibodies elicited by COVID-19 vaccines. The susceptibility of Omicron variant by vaccine-induced neutralizing antibodies are urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolates. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both omicron isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

Finding the Right Problems: Some HREM Applications to Interfaces

1984 ◽  
Vol 42 ◽  
pp. 376-379
Author(s):  
D. Cherns
Keyword(s):  
Grain Boundaries ◽  
High Resolution Electron Microscopy ◽  
Boundary Structure ◽  
Atomic Structures ◽  
Grain Boundary Structure ◽  
Resolution Electron ◽  
Point To Point ◽  
The Right ◽  
New Generation ◽  
Better Than

The use of high resolution electron microscopy (HREM) to determine the atomic structure of grain boundaries and interfaces is a topic of great current interest. Grain boundary structure has been considered for many years as central to an understanding of the mechanical and transport properties of materials. Some more recent attention has focussed on the atomic structures of metalsemiconductor interfaces which are believed to control electrical properties of contacts. The atomic structures of interfaces in semiconductor or metal multilayers is an area of growing interest for understanding the unusual electrical or mechanical properties which these new materials possess. However, although the point-to-point resolutions of currently available HREMs, ∼2-3Å, appear sufficient to solve many of these problems, few atomic models of grain boundaries and interfaces have been derived. Moreover, with a new generation of 300-400kV instruments promising resolutions in the 1.6-2.0 Å range, and resolutions better than 1.5Å expected from specialist instruments, it is an appropriate time to consider the usefulness of HREM for interface studies.

DMSA-scintigraphy in paediatrics: Is the evaluation of the geometric mean necessary for the calculation of the differential renal function?

2001 ◽  
Vol 40 (04) ◽  
pp. 107-110 ◽  
Author(s):  
B. Roßmüller ◽  
S. Alalp ◽  
S. Fischer ◽  
S. Dresel ◽  
K. Hahn ◽  
...  
Keyword(s):  
Renal Function ◽  
Geometric Mean ◽  
Region Of Interest ◽  
Posterior View ◽  
Renal Abnormality ◽  
Anterior View ◽  
Differential Renal Function ◽  
The Mean ◽  
The Right ◽  
To Receive

SummaryFor assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimer-captosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. Aim of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. Methods: 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 ± 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256,300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr]. Results: The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p<0.01). The mean difference between the PFgeom and the PFdors was 1.5 ± 1.4%. A difference > 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference >5% did not show any renal abnormality. Conclusion: The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differntial renal function in orthotopic kidneys, so that in these cases the anterior view is not necesssary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.

scholarly journals Severe Hypertriglyceridemia-Induced Acute Pancreatitis

2021 ◽  
pp. 218-224
Author(s):  
Gyula Molnár ◽  
V. Anna Gyarmathy ◽  
Noémi Zádori ◽  
Péter Hegyi ◽  
Péter Kanizsai
Keyword(s):  
Acute Pancreatitis ◽  
Acute Abdominal Pain ◽  
Blood Cholesterol ◽  
Individual Factors ◽  
Lipid Levels ◽  
Human Monoclonal Antibodies ◽  
Pcsk9 Inhibitors ◽  
Severe Hypertriglyceridemia ◽  
The Right

The prevalence of familial hypercholesterolemia (FH) is about 1 in 200–500 in the general population, but approximately less than 1% of those affected are actually diagnosed. One of the most promising approaches to treat FH is utilizing human monoclonal antibodies. This is a case study describing a 47-year-old male patient who presented to the Emergency Department with acute abdominal pain caused by severe hypertriglyceridemia (HTG)-induced acute pancreatitis (AP). We report the steps necessary for establishing the right diagnosis and the management of HTG-induced AP, which are inevitable for the reduction of severity and mortality. This case study shows that hypercholesterolemia is an underdiagnosed and potentially lethal disease. Once diagnosed, all measures should be considered to control blood cholesterol and lipid levels. The decision to administer PCSK9 inhibitors should not be solely based on economical calculation, but rather individual factors should also be considered to weigh the risk/benefit ratio.

scholarly journals Cure of Chronic Viral Infection and Virus-Induced Type 1 Diabetes by Neutralizing Antibodies

2006 ◽  
Vol 13 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Mette Ejrnaes ◽  
Matthias G. von Herrath ◽  
Urs Christen
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infection ◽  
Inflammatory Mediators ◽  
Neutralizing Antibodies ◽  
Chronic Viral Infection ◽  
Negative Consequences ◽  
Ligand Interactions ◽  
The Right

The use of neutralizing antibodies is one of the most successful methods to interfere with receptor–ligand interactions in vivo. In particular blockade of soluble inflammatory mediators or their corresponding cellular receptors was proven an effective way to regulate inflammation and/or prevent its negative consequences. However, one problem that comes along with an effective neutralization of inflammatory mediators is the general systemic immunomodulatory effect. It is, therefore, important to design a treatment regimen in a way to strike at the right place and at the right time in order to achieve maximal effects with minimal duration of immunosuppression or hyperactivation. In this review, we reflect on two examples of how short time administration of such neutralizing antibodies can block two distinct inflammatory consequences of viral infection. First, we review recent findings that blockade of IL-10/IL-10R interaction can resolve chronic viral infection and second, we reflect on how neutralization of the chemokine CXCL10 can abrogate virus-induced type 1 diabetes.

scholarly journals Antibody titers measured by commercial assays are correlated with neutralizing antibody titers calibrated by international standards

2021 ◽  
Author(s):  
Yu-An Kung ◽  
Chung-Guei Huang ◽  
Sheng-Yu Huang ◽  
Kuan-Ting Liu ◽  
Peng-Nien Huang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Diagnostic Techniques ◽  
International Standards ◽  
World Health ◽  
Serum Samples ◽  
Antibody Titers ◽  
Health Organization

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.

Prevalence and Persistence of Maternal Dengue Neutralizing Antibodies in Infants From Central and Southern Thailand: A Retrospective Cohort Study

2019 ◽  
Vol 31 (4) ◽  
pp. 288-295 ◽  
Author(s):  
Adrienne Guignard ◽  
François Haguinet ◽  
Stéphanie Wéry ◽  
Phirangkul Kerdpanich
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Maternal Antibodies ◽  
Childhood Immunization ◽  
Serum Samples ◽  
Denv Serotypes ◽  
Antibody Titers ◽  
Antibody Kinetics

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.

A Phase 3, Randomized, Open-label, Noninferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (TwinrabTM) Against Human Rabies Immunoglobulin (HRIG)

2020 ◽  
Author(s):  
Kevinkumar Kansagra ◽  
Deven Parmar ◽  
Sanjeev Kumar Mendiratta ◽  
Jatin Patel ◽  
Shuchi Joshi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
World Health ◽  
Human Rabies ◽  
Open Label ◽  
Phase 3 ◽  
Noninferiority Trial ◽  
Rabid Animal ◽  
Antibody Cocktail

Abstract Background Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to search for alternative therapies. This issue has been addressed by developing an anti-rabies monoclonal antibody cocktail. Methods This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with World Health Organization (WHO) category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, TwinrabTM (docaravimab and miromavimab) or the reference arm, human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the 2 arms assessed as percentage of those with rabies virus neutralizing antibodies titers ≥0.5 IU/mL on day 14. Results A total of 308 patients were equally randomized into the 2 arms. In the per-protocol (PP) population, there were 90.21% responders in the TwinrabTM arm and 94.37% in the HRIG arm. The geometric mean of rapid fluorescent foci inhibition test titers in the PP on day 14 were 4.38 and 4.85 IU/mL, for the TwinrabTM and HRIG arms, respectively. There were no deaths or serious adverse events reported. Conclusions This study confirmed that TwinrabTM is noninferior to HRIG in terms of providing an unbroken window of protection up to day 84. This trial in healthy adults with WHO category III exposure from suspected rabid animal also establishes the safety of TwinrabTM in patients with 1 WHO approved vaccine regimen (Essen). Clinical Trials Registration CTRI/2017/07/009038.

scholarly journals Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

2011 ◽  
Vol 18 (9) ◽  
pp. 1406-1409 ◽  
Author(s):  
Beatriz Mariana Abramczuk ◽  
Taís Nitsch Mazzola ◽  
Yara Maria Franco Moreno ◽  
Tatiane Queiroz Zorzeto ◽  
Wagner Quintilio ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Humoral Response ◽  
Vaccine Response ◽  
Serum Samples ◽  
Hiv Exposed ◽  
Exposed Uninfected

ABSTRACTLittle is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, ≥1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders (χ2=10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

scholarly journals Incidence of Infection of Enterovirus 71 and Coxsackieviruses A6 and A16 among Household Contacts of Index Cases in Dong Thap Province, Southern Vietnam

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
C. Q. Hoang ◽  
H. D. Nguyen ◽  
N. X. Ho ◽  
T. H. T. Vu ◽  
T. T. M. Pham ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Age Groups ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Household Contacts ◽  
Significant Difference ◽  
Antibody Titers ◽  
Index Cases

Background. Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. Methods. We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. Results. The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. Conclusions. Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.

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