WHO international standard for SARS-CoV-2 antibodies to determine markers of protection.
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ABSTRACT:
SUBMITTER: Zhu F
PROVIDER: S-EPMC8641955 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Publications
WHO international standard for SARS-CoV-2 antibodies to determine markers of protection.
Zhu Feng F Althaus Thomas T Tan Chee Wah CW Costantini Alizée A Chia Wan Ni WN Van Vinh Chau Nguyen N Van Tan Le L Mattiuzzo Giada G Rose Nicola J NJ Voiglio Eric E Wang Lin-Fa LF
The Lancet. Microbe 20211203 2
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| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other
Project description:SARS-CoV-2 viral load declines from the time of symptom onset; in some studies viral load is higher or persists longer in more severe COVID-19 infection, and viral load correlates with culture positivity. This was a retrospective cohort study of inpatients and outpatients during the first wave of COVID-19 infection in Western Australia, March to May 2020, of the relationship of SARS-CoV-2 viral load (using the First WHO International Standard for SARS-CoV-2 RNA) from symptom onset, by clinical subgroups determined from the public health database and hospital records, using regression analysis. We studied 320 samples from 201 COVID-19 cases: 181 mild, seven severe, 11 critical, and four cases who died (two were also critical cases). At symptom onset the mean viral load was 4.34 log10 IU/mL (3.92-4.77 log10 IU/mL 95% CI, cobas SARS-CoV-2 assay ORF1a Ct 28.9 cycles). The mean viral load change was -0.09 log10 IU/mL/day (-0.12 to -0.06 95% CI). R2 was 0.08 and residual standard deviation 2.68 log10 IU/mL. Viral load at symptom onset was higher for those reporting fever compared to those not reporting fever. Viral load kinetics were not different for gender, age, shortness of breath, or those requiring oxygen. Mean viral load at usual release from isolation at 14 days was 2.5 log10 IU/mL or day 20 was 1.8 log10 IU/mL. Variability in respiratory sample SARS-CoV-2 viral load kinetics suggests viral loads will only have a role supporting clinical decision making, and an uncertain role for prognostication.
| S-EPMC8829673 | biostudies-literature
Project description:BackgroundCycle threshold (Ct) values from SARS-CoV-2 reverse transcription quantitative PCR (RT-qPCR) tests are used to measure viral burden. Calibration to the First WHO International Standard for SARS-CoV-2 RNA may improve quantitative inter-assay agreement.MethodsWHO standard was tested using four emergency use authorized RT-qPCRs to generate calibration curves and evaluate Ct value differences. Harmonization of two assays, Cepheid Xpert Xpress SARS-CoV-2 targeting E and nucleocapsid (N2) [Xpert (E) and Xpert (N2)] and a laboratory-developed test targeting E [LDT (E)], was assessed using 93 positive upper respiratory samples. Platform (target) pairs were compared via Bland-Altman analysis and Passing-Bablok regression.ResultsCt values with the WHO standard were comparable across platforms and targets, except Xpert (N2) for which the mean difference was a median of 3.68 cycles (Interquartile Range, IQR = 3.23 to 3.76 cycles) greater than other platform (target) pairs. Using clinical samples, the mean difference of Xpert (N2) to LDT (E) was 3.64 cycles (95% Confidence Interval, CI =1.51 to 5.76). After calibration, the mean difference of Xpert (N2) to LDT (E) was 0.08 log10 IU/mL (95% CI = -0.56 to 0.71) and the regression was y = 1.00x * 0.08 (95% CI slope = 0.93 to 1.07, 95% CI intercept = 0.28 to 0.42).ConclusionsCalibration to the WHO standard resulted in the harmonization of two RT-qPCR tests, whereas analysis by Ct value alone may have led to erroneous quantitation. Harmonization to the WHO standard has the potential to improve the generalizability of clinical associations with SARS-CoV-2 RNA levels.
| S-EPMC9287539 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.
| S-EPMC7284254 | biostudies-literature
Project description:The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity (in-vitro) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies.
| S-EPMC8628512 | biostudies-literature
Project description:The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients.
| EGAS00001004412 | EGA
Project description:SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.
| S-EPMC10972590 | biostudies-literature
Project description:ObjectivesThe emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralise against the G614 variant.MethodsAntibody profiling against the SARS-CoV-2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS-CoV-2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID-19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR).ResultsProfiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies.ConclusionsCross-reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS-CoV-2. More importantly, there should be negligible impact towards the efficacy of antibody-based therapies and vaccines that are currently being developed.
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Project description:Neutralizing antibody (NtAb) levels are key indicators in the development and evaluation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines. Establishing a unified and reliable WHO International Standard (IS) for NtAb is crucial for the calibration and harmonization of NtAb detection assays. National and other WHO secondary standards are key links in the transfer of IS to working standards but are often overlooked. The Chinese National Standard (NS) and WHO IS were developed by China and WHO in September and December 2020, respectively, the application of which prompted and coordinated sero-detection of vaccine and therapy globally. Currently, a second-generation Chinese NS is urgently required owing to the depletion of stocks and need for calibration to the WHO IS. The Chinese National Institutes for Food and Drug Control (NIFDC) developed two candidate NSs (samples 33 and 66-99) traced to the IS according to the WHO manual for the establishment of national secondary standards through a collaborative study of nine experienced labs. Either NS candidate can reduce the systematic error among different laboratories and the difference between the live virus neutralization (Neut) and pseudovirus neutralization (PsN) methods, ensuring the accuracy and comparability of NtAb test results among multiple labs and methods, especially for samples 66-99. At present, samples 66-99 have been approved as the second-generation NS, which is the first NS calibrated tracing to the IS with 580 (460-740) International Units (IU)/mL and 580 (520-640) IU/mL by Neut and PsN, respectively. The use of standards improves the reliability and comparability of NtAb detection, ensuring the continuity of the use of the IS unitage, which effectively promotes the development and application of SARS-CoV-2 vaccines in China.
| S-EPMC9971588 | biostudies-literature