Agreements between antibody-binding assays and Genscript sVNT were performed using Cohens kappa, crude concordance rate, and area under curve (AUC). Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis. The assay is an electrochemiluminescent. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. The promising preclinical study results presented here demonstrate that ChulaCov19 is highly immunogenic with protective efficacy. Another important limitation is that samples were collected at any time after the last vaccine dose (median 5.2 months (3.16.4)); Swadzba et al. In the case of Omicron variants, psVNT50 NAb GMT results against Omicron BA.1 and BA.4/5 subvariants showed that the heterologous prime/boost regimen was more efficient (84-172 folds increase) in inducing NAb against BA.1 and BA.4/5 subvariants compared to homologous CoronaVac or AZD1222 immunization. The Abbott Architect SARS-CoV-2 IgG II assay, run under an emergency use authorization from the FDA, is quantitative test designed to detect IgG antibodies to the spike protein of SARS-CoV-2 in serum and plasma from individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. Usually your antibody levels will go up after getting a vaccine or having an infection. The results of available anti-SARS-CoV-2 IgG antibody tests may be interpreted in the following way: In a person never vaccinated: Testing positive for antibody against N (nucleocapsid protein), S (spike protein), or RBD (receptor-binding domain of S protein) indicates prior infection. Eichinger, K. M. et al. endobj Ferrara, F. & Temperton, N. Pseudotype Neutralization Assays: From Laboratory Bench to Data Analysis. In this interview conducted at Pittcon 2023 in Philadelphia, Pennsylvania, we spoke to Dr. Chad Merkin, Director of the International Institute for Nanotechnology, about his work developing next-generation nanomaterials for medical applications. Vaccines (Basel) 9, (2021). Nat Commun 13, 4710 (2022). 4c. Percentage of virus infectivity in virus control (VC) and samples were calculated based on OD of cell control (CC), infectivity (%) = (OD of CC OD of sample) x 100. Philippe Cartlamy, Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint. At 24hr post-transfection, both intracellular and secreted S protein expressions were analyzed. This is a surrogate marker indicative of vaccine effectiveness, or the sterilizing immunity as reported in the previous study27. Buschmann, M. D. et al. Results are reported as AU/mL. In supernatant, we could detect both intact S and cleaved S1 and S2 (Fig. The results resembled those observed in the panel that used a commercial recombinant S-trimer instead of transfected supernatant. Sci Rep 11, 22777 (2021). HEK293T-hACE-2 cells, prepared by transduction of HEK293T cell line with lentiviral habouring hACE-2 gene, used for hACE-2 binding assay was gratefully provided by Dr.Navapon Techakriengkrai55. It was subcloned into pUC-ccTEV-A101 using Afe I and Spe I restriction sites58. : grant funding acquisition. Preferred: 5 mL blood in GOLD SST tube.Also Acceptable: Orange RST, pearl PPT, serum from red top, plasma from EDTA tube. Nature 584, 450456 (2020). Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines. Google Scholar. Further investigation using different techniques, such as viral isolation and titration from the collected tissues is required to draw a definite conclusion. Having more antibodies means your body can fight infection better than having fewer antibodies. SARS-CoV-2 is the name of the virus that causes coronavirus disease 2019 (COVID-19). E.P., C.K., D.W., and K.R. The team also determined whether the S1 subunit influences mature neurons during cell exposure. Meta-analysis shows phytosterol-fortified foods effectively lower LDL cholesterol levels. 6c) may be due to RT-qPCR, a highly sensitive method detecting the free viral RNA from disintegrated virus. Bowen, J. E. et al. PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US. Molecular-based testing is used to diagnose COVID-19, and serologic testing of antibodies specific to SARS-CoV-2 is used to detect past infection. Boosting with ChulaCov19, although not statistically significant, it could enhance the IFN- positive T cells by approximately 6.5 folds (p=0.1523) of the magnitude of T cells response in CoronaVac-primed mice (273 SFC/106 splenocytes). The goal of experiment 2 was to assess the potential role of ChulaCov19 as a booster in a setting of heterologous primed with other COVID-19 vaccine platforms. LMICs received these vaccines much later and in shorter supply, as evidenced by the most recent statistic (as of 31 August 2022) that in several African countries less than 30% of the population has received at least one vaccine dose20. Centrifuge RED TOP or EDTA tube and aliquot serum/plasma into plastic aliquot tube. PubMed Central Correspondence to 1b). Additional quality control to ensure the absence of double-stranded RNA (dsRNA) and endotoxin contamination prior to encapsulation into lipid nanoparticles (LNPs) were performed as described previously60. van Doremalen, N. et al. Chen, X. et al. This was consistent with the prior study in K18-hACE2 that intranasal inoculation with the similar range of virus caused death within 1 week22. Stphane Blachier, To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The mRNA vaccine technology transfer hub [updated 21 June 2022. Translating a Thin-Film Rehydration Method to Microfluidics for the Preparation of a SARS-CoV-2 DNA Vaccine: When Manufacturing Method Matters. PubMed Central WHO. SARS-CoV-2 delta variant infection in domestic dogs and cats, Thailand. Therefore, we suggest specific BAU/ml adjusted thresholds for the four commercial antibody assays (Abbott, Beckman, Roche, and Siemens), which can be used to guide the use of PreP in immunocompromised patients. The female/male ratio was 67/33, and the median age was 47 years (IQR 3463). Its worth to mention that, as of now, theres no widely accepted cutoff value for immunity in immunocompromised patients, but some studies have suggested that antibody levels cut off may be associated with protection against COVID-19. Kunkalikar, Bhavana. Moreover, the feasibility of large-scale production as well as rapid adaptability to new variants are major advantages of the mRNA production platform. Laboratoire AlphabioBiogroup, Marseille, France, PubMed Statistical significance was determined by two-sided MannWhitney test. The total volume of 50l of viral RNA was obtained from each sample. Polack, F. P. et al. ROC curves for each antibody binding assay according to Genscript sVNT. Guilhem Cavaille, Article The capped mRNA was purified by cellulose columns purification59. ADS J Exp Med 184, 485492 (1996). Vacharathit, V. et al. Beyond the techniques used for the viral detection, the inverse correlation between vaccine dosage and tissue viremia might be the results of the quality of T cell response induced by the high vaccine dosage. Nat Commun 14, 2309 (2023). At week 18, the NAb against WT (Wuhan-Hu1) and Delta (B.1.617.2) decreased approximately 2-fold but not statistically significant when compare with week 5 titers. All isolates were quantitated by tissue culture infectious dose TCID50 using the Reed-Muench method. Prefusion RSV F Immunization Elicits Th2-Mediated Lung Pathology in Mice When Formulated With a Th2 (but Not a Th1/Th2-Balanced) Adjuvant Despite Complete Viral Protection. The reactions were then stopped with 50L of 0.16N sulfuric acid. Winkler, E. S. et al. The slides were dehydrated in 60C dry oven until completely dry and then dipped in Xylene before mounting with a mounting medium. News-Medical, viewed 01 May 2023, https://www.news-medical.net/news/20230427/Neurological-phenotypes-induced-by-SARS-CoV-2-spike-protein-in-neurons.aspx. ChulaCov19 vaccination could provide 100% protection from severe clinical signs and mortality in mice. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 - PLOS Frequently Asked Questions About COVID-19 Testing for Providers & Clients At week 3 after dose 1, NAb were still detected in all animals in the 10g group, and 5/6 animals in the 1g group. The score (0-5) was assigned according to the percent distribution of fluorescent-positive cells. The Abbott Architect SARS-CoV-2 IgG II assay, run under an emergency use authorization from the FDA, is quantitative test designed to detect IgG antibodies to the spike protein of SARS-CoV-2 in serum and plasma from individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. Ramasamy, M. N. et al. Please note that medical information found % Furthermore, the immunity in immunocompromised individuals may be less robust than in healthy individuals and may wane more quickly. PN20-06). In these preclinical studies in mice, we have demonstrated that ChulaCov19, a secreted, prefusion non-stabilized ectodomain spike mRNA vaccine, elicited robust Spike-specific antibody and T-cell responses which has also translated into efficacy in protecting transgenic mice from SARS-CoV-2. Some must be performed in a laboratory by trained personnel, some can be performed at the point of care, and others can be . First bivalent COVID-19 booster vaccine approved by UK medicines regulator). Agreement between antibody binding assays and Genscript sVNT positive and negative results according to optimal cutoff values determined for each assay. The LNP- encapsulated mRNA were characterized for their size, polydispersity using a Zetasizer (Zetasizer Nano DS, Malvern, UK), encapsulation efficiency, and shipped on dry ice and stored at 80 oC until use. In contrast, undetectable fluorescent signals for S proteins were observed when HEK293T-hACE-2 were incubated with supernatant from untransfected cells (Fig. There was no detectable viremia in mice in both high or low-dose vaccine-treated groups while an average of 7.71104 GE/mL (ranged from 1.03103 3.75105 GE/mL) of viral RNA was detected in PBS-received mice, Fig. Neurological phenotypes induced by SARS-CoV-2 spike protein in neurons For intracellular analysis, cells were fixed, permeabilized with ice-cold acetone and stained with 1:200 dilution of monoclonal-anti-RBD (R&D Systems, MN, USA), polyclonal-anti-S1, -anti-S2 antibodies (Sino Biological, Beijing, China), or 1:5,000 dilution of pooled convalescent serum (PCS) collected in 2020. Recombinant S protein with S1/S2 cleavage site abolished (ACROBioSystems, China) was used as positive control both in HEK293T-hACE-2 binding assay and western blot. T-cell responses to SARS-CoV-2 can be indirectly tested with antigen tests (such as Elispot) that tests for cytokines produced (i.e. 11 Antibody tests may help identify past SARS-CoV-2 infection if performed two to four. In-depth investigation of viral burden in different tissues as well as T cells quality induced by various vaccine dosages are still required. )5ul~eC}=,t?~]r6T5\OQhyN=8. a Kinetics of total IgG at 2 weeks after receiving 1 or 2 doses of 0.2, 1, 10, and 30g of ChulaCov19. Regarding the vaccine construct characterization, protein expression studies revealed S proteins were expressed both in intracellular and extracellular compartments when detected either by specific antibodies or patient sera (Fig. although all assays showed good agreement with the Genscript sVNT, they were not interchangeable, even when converted to BAU/ml [10]. 6b. For the Siemens assay, the optimal cutoff was within the same range as the reference cutoff (270 BAU/ml). The FFPE tissue slides were deparaffinized and treated with hydrogen peroxide (10min at room temperature) followed by target retrieval in 1X target retrieval solution in a steamer of at least 99C for 15min. Bleeding was performed at 2 weeks following each dose (and at week 18 for Experiment 3). 2023. Inclusion criteria were data from immunocompromised patients undergoing chemotherapy and/or biotherapy, aged over 18, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) from three to six months before sampling collection. Bar-On, L. et al. The induced NAb was highly specific to the original variant, however, cross-neutralization against the VOCs was also observed. No serologic tests for SARS-CoV-2 are approved by the FDA; some, but not all, commercially available serologic tests for SARS-CoV-2 have received EUAs . By using immunofluorescent assay, employing RBD-, S1-, S2-specific antibodies or PCS, the S proteins were observed within the cytoplasm of transfected cells while untransfected cells were negative for fluorescent signal (Fig. Available from: https://www.science.org/content/article/new-crop-covid-19-mrna-vaccines-could-be-easier-store-cheaper-use (2022). Bellamkonda, N. et al. The mid-point titers were determined in duplicate assays from 5 mice in each group. PLoS One 16, e0248007 (2021). Bars represent the GMTs and 95% CI for each group. Each dot represents an individual animal. Even though most COVID-19 patients are asymptomatic or only mildly symptomatic2,3,4, the virus is still eminently transmissible even during the early phases of the illness. Tseng, C. T. et al. This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. Clinical studies are ongoing to evaluate the effectiveness and safety of these medications in immunocompromised individuals and using them as PrEP. The RT-qPCR data showed that both doses of vaccine prevented the expression of SARS-CoV-2 viremia at 5 or 6 days after viral inoculation. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Infect Dis Poverty 11, 53 (2022). Per manufactures package insert protective level is 50.0 AU/mL. As the Omicron subvariant BA.4/5 is currently spreading worldwide, we have also assessed cross-neutralization and found that the NAb GMT measured by psVNT50 against BA.4/5 in homologous ChulaCov19 vaccination or heterologous boosted with ChulaCov19 groups were significantly better than either of the CoronaVac or AZD1222 homologous vaccination (Fig. On Day 5, significant weight reduction (p<0.05) was observed in control group when compared with the vaccinated groups. Based on these studies, a threshold of 264 BAU/ml antibody was used as a recommendation for the use of PrEP in SARS-CoV-2 in France, and extrapolated to immunocompromised patients [9]. Bars represent the meanSD of S-specific IFN- positive T cells after stimulated with overlapping peptide pools spanning the SARS-CoV-2 S1 (pooled #1-5) and S2 (pooled #6-10). p<0.05 and p<0.01 are indicated by * and **, respectively. Whether differences in response impact vaccine efficacy needs further study. Day 6 after the viral challenge (week 5+6 days), there was a slight decline of NAb titers in both groups but not statistically significant when compared to week 5, p=0.1126 and p=0.4437 for 10 g and 1 g groups, respectively. Nl5AMM(&R/ In the nasal turbinate, vaccinated mice exhibited luminal accumulation of mucus and/or fibrin, albeit only minimal to mild amounts. Vaccines (Basel) 9, 874 (2021). So there is not enough data available to comment on the uptake of this therapy yet and raises the question in cases of previous infection or vaccination, the need to assess the SARS-CoV-2 antibody level for therapy decision making [1820]. At 2104 PFU of SARS-CoV-2 inoculum, PBS-vaccinated mice displayed clinical symptoms or weight loss within 1 day and all mice succumbed by day 6. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. According to French regulations, the study was approved by the French ethics committee (Health Data Hub, approval number: F20211217094518). All data were fully anonymized before the analysis. In addition, there was no anamnestic antibody response detected in the ChulaCov19 vaccinated mice after viral challenge (Fig. The researchers believe that the study findings provide new insight into the activity of SARS-CoV-2 S proteins beyond their well-established functions in viral attachment and entry. 200 0 obj <>]/Filter/FlateDecode/BitsPerComponent 8/Length 2211/Height 275>>stream The geometric mean titers (GMTs) of NAb against wild-type (WT, Wuhan-Hu1) virus are 1,280, 11,762, 54,047, and 62,084, respectively. PubMed Central Boxplots for each antibody binding assay according to Genscript sVNT positive and negative results. About the study. CAS Vacharathit, V. et al. Results were determined as a ratio of the signal of the samples to the average signal of calibrators. Lv, J., Wu, H., Xu, J. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Previous study by Eichinger KM, et al. Samples from 69 patients were analyzed. 8 more], Department of Infectious Diseases and Internal Medicine, Hpital Europen, Marseille, France, Affiliation: https://www.biorxiv.org/content/10.1101/2023.04.24.538161v1, Pregnant women show unique immune response to COVID-19, Study indicates that SARS-CoV-2 has evolved to gain increased replicative fitness and become well-adapted in epithelial cells of human airways, High-protein diet counters adaptive thermogenesis in prediabetic individuals. Detection of antibodies to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances detection of infection Recommendations based on only one study is not prudent. The 4-week gap was used according to the preclinical study protocol of ChAdOX-vectored vaccines65,66. During the experiments, mice were maintained at 2022C and a relative humidity of 4510% on a 12h light/dark cycle. 1a). The study identified the number of pulses per electrode as the most prominent characteristic that differentiated the spike protein-treated wells from the control wells. Secreted mouse IFN- was captured by anti-mouse IFN- (AN18) monoclonal antibody at dilution of 1:2,500 (Mabtech, Nacka Strand, Sweden) precoated on 96-well nitrocellulose membrane plates (Merk Millipore, Darmstadt, Germany). CK, EP and KR were funded by the National Vaccine Institute (NVI), grant No. These results reflect that ChulaCov19 was highly immunogenic and induced a Th1-skewed response in mice. Lancet. However, there was no discernible difference in burst activity between S1-treated and the control wells. SARS-CoV-2 Antibody Profile, Nucleocapsid and Spike 199 0 obj <>stream Philippe Halfon, 01 May 2023. The NAb titers were drastically enhanced after the second dose was given, p<0.01 for all dose ranges. N Engl J Med 383, 24392450 (2020). Presently, the pandemic is still surging in many countries. It was also evaluated for the protective efficacy in transgenic mice expressing human angiotensin-converting enzyme-2 (ACE2), Fig. How are the results reported for the anti-nucleocapsid antibody test, and what is the clinical significance? However, this was still far lower than using homologous ChulaCov19 or AZD1222-prime/ChulaCov19-boost immunization regimens (Fig. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). Note: tissues from 3/5 animals in control group were collected at day 5. Objectives: The aim was to determine the antibody response against SARS-CoV-2 spike protein and nucleoprotein using four automated immunoassays and three ELISAs for the detection of total Ig antibodies (Roche) or IgG (Abbott, Diasorin, Snibe, Euroimmun, Mikrogen) in COVID-19 patients. & Berzofsky, J. Fact Sheet for Healthcare Providers Please use one of the following formats to cite this article in your essay, paper or report: Kunkalikar, Bhavana. Sylvie Jordana, Sci. Even as SARS-CoV-2 mutates, some human antibo | EurekAlert! Image Credit: whitehoune/Shutterstock.com. COVID-19 antibody testing is a blood test. This assay detects antibodies that block the interaction of SARS-CoV-2 with its entry receptor angiotensin-converting enzyme 2. The same dosage of approved vaccines were used with a dose of 5g ChulaCov19 (1/10 of the human dose used in Phase 2 Trial). In contrast, ChulaCov19 immunized mice, both 1g and 10g doses enabled 100% survival compared to full mortality rate in PBS-immunized mice. News-Medical. Fact Sheet for Healthcare Providers Labcorp test details for SARS-CoV-2 Semi-Quantitative Total Antibody, Spike . as a booster dose in mice that had been primed with CoronaVac or AZD1222 (Experiment 2). Blood was collected at wk0, wk2, wk3, wk4+6 and wk5+6 days for antibody kinetic analysis (Fig. 2c). 6b, c, Table1). Two were quantitative: Abbott SARS-CoV-2 IgG II Quant-test (Abbott) (Abbott France, Rungis, France) with 50 arbitrary units (AU)/ml as a threshold for positivity, and Roche Elecsys anti-SARS-CoV-2 S (Roche Diagnostics France, Meylan, France) with 0.8 AU/ml used as a threshold for positivity. Cell nuclei were counter stained with 4, 6-diamino-2-phenylindole hydrochloride (DAPI) (Sigma-Aldrich, USA). The S protein facilitates virus attachment and entrance into the host cell. The authors would like to thanks Dr.Navapon Techakriengkrai, Faculty of Veterinary Science, Chulalongkorn University for providing HEK293T-hACE-2 cells. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Interpreting SARS-CoV-2 Diagnostic Tests: Common Questions and Answers ];V^srE]DwCyTPre_fyG;Cb@*\d$ j '-|,!]jF/J9r\s%3! Provided by the Springer Nature SharedIt content-sharing initiative. The differences in the commercial assays used in this study are related to the components of the tests (the spike antigen epitopes used, the different isolates of the SARS-CoV-2, and the quantification of either total antibodies or only IgG) [2123].
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