The limitation of this study includes the limited samples for tissue viremia after challenge. sample is stable for 7 days at 2-8C once separated from a clot or red blood cells, or in a gel separator tube. PLoS ONE 18(4): No significant difference among agreements was observed. The encapsulated mRNA-LNP was characterized by various parameters including size, polydispersity (PDI) and mRNA encapsulation efficiency at 1, 6, and 12 months after manufacture. Source data are provided with this paper. A. Vaccines (Basel) 10, 613 (2022). In just over 2 years into the pandemic, more than 10 variants of the virus have been reported, of which, 5 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B1.1.529) have been categorized by WHO as variants of concern (VOCs)7. Spin within 24 hours and prior to shipment. S-specific IFN- positive T cells were determined in duplicate assays from 5 mice in each group. At this time-point, 10g dosed mice induced significantly higher in GMTs of micro-VNT50 titers than 1g dosed mice (p=0.0065). Vacharathit, V. et al. Kunkalikar, Bhavana. Nat Immunol 21, 13271335 (2020). Protection against COVID-19 is thought to depend on the presence of specific antibodies against the virus, as well as the function of other components of the immune system such as T cells. Tseng, C. T. et al. Meta-analysis shows phytosterol-fortified foods effectively lower LDL cholesterol levels. A SARS-CoV-2 probe (RNAscope Probe, V-nCoV2019-S, Advanced Cell Diagnostics ACD, Newark, CA (ACD, 848561)) was used. KR, DW, MGA, CK, EP, and SB are co-inventors of the submitted ChulaCov19 mRNA vaccines Patent. The average decline from peak to euthanasia among PBS-receiving mice was 17%. The vaccine inequity issue is a huge challenge to healthcare in LMICs. 11 Antibody tests may help identify past SARS-CoV-2 infection if performed two to four. mRNA capping was performed by the trinucleotide cap1 analog, CleanCap (TriLink Biotechnologies, San Diego, CA, USA). The program is funded by the Government of Thailand. Nat Commun 14, 2309 (2023). Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. The study suggested that S1 is responsible for decreasing burst activities of neuronal populations when cells are exposed early in the course of development. Statistical analysis was performed using GraphPad Prism 9.0 software (San Diego, CA, USA). 8aU::fT23 Results were expressed as spot-forming cells (SFCs)/106 splenocytes after subtraction of the spots from negative control wells. Recombinant S protein with abolished S1/S2 cleavage site was used as positive control in HEK293T-hACE-2 binding assay (right panel of 2b) and western blot (right lane of each panel in 2c). The average body weight by group from week 5 to week 5+6 days was demonstrated in Fig. The GMT of micro-VNT50 titers at week 5 were 15,343 and 4424 in the 10 g and 1 g groups, respectively, p=0.0325. 5a). Similar findings were also observed in BA.4/5 subvariant (Fig. Quantitative SARS-CoV-2 anti-spike responses to Pfizer-BioNTech and Oxford-AstraZeneca vaccines by previous infection status SARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Nature 584, 450456 (2020). In brief, 100ng of recombinant S-trimer (ACROBioSystems, China) were coated to the 96-well plates. Function of the expressed S protein was also confirmed as it could bind to hACE-2 similar to those of stabilized trimeric spike (Fig. The SARS-CoV-2 Omicron variant emerged in late 2021 and spread quickly. The plasmid was propagated in E. coli (Stbl3, Invitrogen, Carlsbad, CA, USA) and extracted by EndoFree Giga Kit (Qiagen, Hilden, Germany). Among the 1g group, only one tissue had very few positive cells, the nasal epithelium. The NAb titers were drastically enhanced after the second dose was given, p<0.01 for all dose ranges. However, there was no discernible difference in burst activity between S1-treated and the control wells. WIPO (2020). Solid reference line represents 264 binding antibody units (BAU)/ml cutoff (2.4 Log). Kairat Tabynov, Nurkeldi Turebekov, Kaissar Tabynov, James Logue, Robert M. Johnson, Matthew B. Frieman, Yi-Jiun Lin, Meei-Yun Lin, Chia-En Lien, Susanne Rauch, Nicole Roth, Benjamin Petsch, Felicity C. Stark, Bassel Akache, Martin Handfield, Maarten Swart, Joan van der Lubbe, Roland Zahn, Jessica Andries, Wildriss Viranaicken, Philippe Despres, Nature Communications Feikin, D.R. Background To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. 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 . We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients. Klemis, V. et al. Secreted S protein was also subjected for analysis of its binding capability to hACE2. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. As previously observed by Perkmann et al. broad scope, and wide readership a perfect fit for your research every time. Article In the present study, researchers quantified the neurological phenotypes induced in neurons by the SARS-CoV-2 S protein. 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. 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]. Statistical analysis significance was determined by two-sided MannWhitney test. Furthermore, the antibody rescue experiment confirmed the role of S1 in suppressing burst activities and highlighted the protective function of anti-S1 antibodies as well as the significance of RBD in modulating neuronal phenotypes. One-day-old Vero E6 cells were used for measuring the level of neutralizing antibodies by live-virus micro-neutralization (micro-VNT50). Challenge studies show that ChulaCov19 protects human-ACE-2-expressing female mice from COVID-19 symptoms, prevents viremia and significantly reduces tissue viral load. All authors reviewed the results and approved the final version of the manuscript. Vaccines (Basel) 9, 874 (2021). It may also mean your body's immune system has generated a response to a prior COVID-19 infection. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Optimal cutoffs for distinguishing positivity were calculated using logistic regression on Genscript sVNT binary results (negative/positive), prior to the Youden index maximization approach on receiver operating characteristic curve results. Immunogenicity and Safety of ChulaCov19 BNA159 Vaccine as a Booster Dose in Adults). 007/2563), and the Armed Forces Research Institute of Medical Sciences, AFRIMS (IACUC approval no. The micro-VNT50 titers was calculated as the reciprocal serum dilution that neutralized 50% of virus observed in virus control wells using probit analysis, SPSS program71. 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. Laboratoire AlphabioBiogroup, Marseille, France, These results suggest that both dosing regimens effectively protected the mice from detectable levels of circulating virus. All assays showed a high AUC for prediction of positive and negative results of Genscript sVNT (AUC > 0.90 for all) (Fig 2). CAS 7, eabi5246 (2021). Patrick Philibert, Statistical significance was determined by two-sided MannWhitney tests. 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. 9, 1225 (2020). For group 1 and 2, there were 6 mice/group immunized intramuscularly via quadricep muscles with 2 doses, 3 weeks apart of ChulaCov19 at dose of 1g and 10g, respectively. Splenocytes from mice immunized with various dosages of ChulaCov19 (Experiment 1) were analyzed as summed frequency of S-specific IFN- positive T cells (Fig. World Health Organization. These factors might make it difficult to draw a strong conclusion on vaccine efficacy from the current of experiments. 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. No positive detection of viral RNA was present in the 10g group of animals analyzed by ISH. However, this was still far lower than using homologous ChulaCov19 or AZD1222-prime/ChulaCov19-boost immunization regimens (Fig. A vaccine efficacy of 80% was achieved with 264 binding antibody units (BAU)/ml (95% confidence interval [CI]: 108, 806) for anti-spike, and 506 BAU/ml (95% CI: 135, over limit) for anti- receptor-binding domain (RBD) antibodies. There are currently a few monoclonal antibody cocktails (such as bamlanivimab, casirivimab, and imdevimab together) that have been authorized by the US FDA for emergency use for the treatment of COVID-19 in certain population and similar medications have been authorized in other countries. The data as well as the p values suggested that the anti-S1 antibody reversed the impact of S1 on bursting activities. More importantly, in partnering with a domestic vaccine manufacture, BioNet Asia, ChulaCov19 can now be manufactured and formulated locally54. The results resembled those observed in the panel that used a commercial recombinant S-trimer instead of transfected supernatant. The bands corresponding to S1, S2 and intact S (S0) were detected. PN20-06). Koonpaew, S. et al. 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. wxWd~{Trru%m#97Z=}<8boK.3E@KT>1oW#!7q%7uJ?IC5 .iM!. In the detection step, staining of the living cells with 0.02% neutral red (Sigma Aldrich, USA) in 1X PBS (Invitrogen, Carlsbad, CA, USA) was used instead of viral protein staining employing anti-nucleocapsid (1:5,000) used in Experiment 1. However, harmonization of neutralizing antibody titers is necessary to determine a common threshold using which vaccine protection can be predicted. 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. Note; the IgG2a/IgG1 ratio of 10g and 30g immunized mice were not analyzed due to limited volume of serum samples. Roche Diagnostics, Inc. - Elecsys Anti-SARS-CoV-2 S. This test detects human SARS-CoV-2 antibodies . Article 1, 8 (2018). For tissue samples, RNeasy Mini Kit (QIAGEN, Hilden, Germany) was used following manufacturer instructions. 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. Ramasamy, M. N. et al. c SARS-CoV-2 viral RNA copies with SD detected by RT-qPCR in serum and homogenized tissues of challenged animals analyzed at euthanasia date (Day 6). Biomedicines 10, 1464 (2022). The NT50 titers against WT and Delta variants increased 7- to 14-fold when using the heterologous approach with ChulaCov19 as compared to the homologous immunizations with CoronaVac or AZD1222 (Fig. What are the benefits of exercise on cardiovascular health. The NT50 titer decrease found in our study was similar to those of other approved vaccines as the titers against BA.1 and BA.4/5 decreased by more than 8-10 folds when compared to the WT virus46,47,48. Alexander-Miller, M. A., Leggatt, G. R., Sarin, A. Slider with three articles shown per slide. Experiment 3: antibody durability and effect of 3rd dose of ChulaCov19 study, mice were immunized twice with 3 weeks interval with 5g of ChulaCov19 (1/10 of human dose used in clinical trial) then boosted again at week 20. Although several SARS-CoV-2 vaccines used an engineered S protein to abolish S1/S2 cleavage or to stabilize the prefusion stage35,36,37, vaccines encoding unmodified S protein are also worth exploring as its structure is the same as native viral protein. On the basis of these data at present anti-SARS CoV-2 serological assays' results are not interchangeable, and, more importantly, individual immune monitoring should be performed with the same method. 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. Slides were then incubated with protease plus for 20min at 40C in a HybEZTM oven (ACD) and subsequently incubated with the SARS-CoV-2 specific probe for 2h at 40C in the HybEZTM oven. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19). Prevalence of Asymptomatic SARS-CoV-2 Infection. Adv. Differences were considered significant at p<0.05 with exact p-values shown. p<0.05 and p<0.01 are indicated by * and **, respectively. The average reduction of viral load in tissues of both vaccine-treated groups relative to the control was 99.9-100%. Further investigation using different techniques, such as viral isolation and titration from the collected tissues is required to draw a definite conclusion. Each dot represents an individual animal. Post-translational modifications were also similar to those observed on SARS-CoV-241. Experiment 1: (a) Live-virus microneutralization (micro-VNT50) titers against WT (Wuhan-Hu1) live-virus at two weeks after receiving each vaccine dose. If testing will be delayed more than 7 days store at -20C or colder. Rotshild, V., Hirsh-Raccah, B., Miskin, I., Muszkat, M. & Matok, I. Cite this article. The study also noted that the RBD may be accountable for the suppression of neuronal signals. S1 neutralized by antibodies did not result in a significant decrease in burst activity compared to the control, whereas the conventional S1 treatment on day zero did reduce burst activity. 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. Four antibody binding assays were used for serological testing according to the instructions of the manufacturer. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. plasma, or dried blood spot (DBS) using the S1 domain of the recombinant SARS-CoV-2 spike protein expressed in the HEK 293 human cell line . Challenge study was conducted in ABSL-3 facility at AFRIMS, Bangkok, Thailand. Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains. Splenocytes were collected at 2 weeks after the second dose (Experiment 1 & 2). Blood was collected at wk0, wk2, wk3, wk4+6 and wk5+6 days for antibody kinetic analysis (Fig. Such unusual characteristics, in conjunction with a highly contagious profile, resulted in the rapid spreading of the virus worldwide. Get the most important science stories of the day, free in your inbox. The SARS-CoV-2 Spike IgG test shows the level of COVID-19 antibodies you had in your blood when you gave the blood sample. Covid-19 Tracker: More Than 12.6 Billion Shots Given [updated 31 August 2022; cited 2022 31 August]. From nanoparticle-based enrichment to mass spec refinements, they explore how these tools facilitate unbiased, deep, and rapid proteomics. volume14, Articlenumber:2309 (2023) In addition, the pseudovirus neutralization test (psVNT50) against lentiviral pseudovirus bearing a codon-optimized spike gene, described previously69,70, was also used for determination of the neutralizing activity against WT, (Wuhan-Hu1), Alpha (B.1.1.7), Beta (B.1.351), Delta (B1.617.2), and Omicron (B1.1.529; BA.1 and BA.4/5 subvariants) variants. Cohen J. Please note that medical information found n=5 per group for Experiment 1, 2 and 3. b Challenge study in K18-hACE2 transgenic mice, n=6 in vaccinated groups and n=5 in control (PBS-receiving) group. a Intracellular S protein expression examined by immunofluorescent assay employing anti-RBD, -S1, -S2 or PCS as primary antibody, the nuclei were counter stained with DAPI (blue). 3b). In a recent study posted to the bioRxiv* preprint server, researchers explored the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and burst activities in neurons. In contrast, ChulaCov19 immunized mice, both 1g and 10g doses enabled 100% survival compared to full mortality rate in PBS-immunized mice. Sci Rep 12, 8403 (2022). This study also indicated that neutralizing S1 restores neuronal discharge activities to control levels. By clicking "Allow All" you agree to the storing of cookies on your device to enhance site navigation, 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. % Thus, most recently approved vaccines employ full-length S (with or without modification) or whole virus (inactivated) as a target antigen19. When RT-qPCR was used, although viral RNA was still detected in some tissues, both dosages demonstrated a 99-100% reduction of viral RNA in tested tissues when compared to the control group. At week 5, mice were challenged intranasally with 2104 pfu of WT SARS-CoV-2. 5b). 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. Tracking SARS-CoV-2 variants 2022 [updated 11 August 2022; cited 2022 19 August]. x2- p` ` \0`0e`X{StAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA^@%&D7(mylkv Although the currently available vaccines do not completely prevent infection, they are efficacious in reducing severe symptoms of infected individuals11. Pardi, N. et al. Among the recently approved vaccines, mRNA modality seems to be the most efficacious as it induces high levels of desired immune responses and protects from severe symptoms16,17. Centrifuge GOLD SST tube and route to Eastlake Virology (EVIR rack 81). The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four . Broad and timely access to effective vaccines in LMICs, particularly the most under-served settings, has always been limited during past pandemics and this has extended to COVID-1920. The test can provide information about how your body reacted to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to the antibody results, the magnitude of T cell response was found to be dose-dependent but peaking at the 10-g dosage. Baseline characteristics are shown in Table 1. Route to Eastlake Virology (EVIR rack 81). In all past pandemics, as well as the ongoing one with COVID-19, access to effective vaccines in a timely manner and has been severely limited in these countries. 4d). ADS Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. Further information on research design is available in theNature Portfolio Reporting Summary linked to this article. On day zero, neurons obtained from newborn P1 mice were treated with recombinant SARS-CoV-2 S protein and S1 and S2 S2 subunits. Provided by the Springer Nature SharedIt content-sharing initiative. In this study, ChulaCov19 was shown to be highly immunogenic, in a dose-responsive relationship, even when immunized with very low amount of 0.2g as measured by both live- and pseudovirus-neutralization assays. et al. ChulaCov19 was further compared to two approved vaccines (CoronaVac and AZD1222), either in a homologous prime/boost setting or heterologous one (i.e. Frdrique Retornaz, Ferrara, F. & Temperton, N. Pseudotype Neutralization Assays: From Laboratory Bench to Data Analysis. Discover a faster, simpler path to publishing in a high-quality journal. SARS-CoV-2 is an enveloped positive-sense single-stranded RNA beta coronavirus with a 30 kb polycistronic genome that encodes non-structural proteins (ORF1a and ORF1b, that are processed into Nsp1-16) at the 5-end, and structural proteins (S, E, M and N), and several other accessory factors (ORF3a . Together with the emergence of new VOCs, a booster dose (either homologous or heterologous vaccine modality) is required to enhance the vaccine effectiveness15. S-specific IgG measurement was performed employing indirect ELISA as described previously56,67. Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine. Three out of five mice reached euthanasia criteria on Day 5, and symptoms progressed for the remaining two mice which met the criteria on Day 6. The function of secreted S protein also determined whether it could bind to hACE-2. Elecsys Anti-SARS-CoV-2 serology assay is intended for the detection of IgM and IgG antibodies to SARS-CoV-2 in human serum and plasma. Animals were immunized IM with 1g or 10g of ChulaCov19 at weeks 0 and 3. The 4-week gap was used according to the preclinical study protocol of ChAdOX-vectored vaccines65,66. Splenocytes were collected at 2 weeks after the last dose (Experiment 1 & 2) for assessment of spike-specific IFN- T-cell using ELISpot assay (Fig. Lipid nanoparticles). Watanabe, Y. et al. WHO. EBioMedicine 77, 103902 (2022). Signals of S protein stained by RBD-, S1-, S2-specific antibodies or PCS were detected on unpermeabilized HEK293T-hACE-2 cell after incubation with transfected supernatant. All p values <0.05 were defined as statistically significant. This observation correlates with that of a recent clinical study report53. endstream T-cell responses to SARS-CoV-2 can be indirectly tested with antigen tests (such as Elispot) that tests for cytokines produced (i.e. Lancet 396, 19791993 (2021). In female BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 g elicits robust neutralizing antibody (NAb) and T cell responses in a dose-dependent relationship. Current SARS-CoV-2 antibody tests detect IgM or IgG to viral spike or nucleocapsid proteins. At 24hr post-transfection, both intracellular and secreted S protein expressions were analyzed. The vaccine effectiveness is varied due to several factors such as the emergence of new variants, study population, and prevalence of the outbreak during the period the studies were conducted11,12,13. Quantitative data were reported using median and interquartile range (IQR), and qualitative data were reported using frequency and percentage. Most convalescent patients tested with Tspot are reactive depending on which antigen is tested and which technique is used. Therefore, the data indicated that the S1 subunit affected neurons only when the cells were exposed during the earliest stages of development. : reagent preparation and analysis, E.P., C.K., and K.R. Cell 182, 5058.e58 (2020). Six-day post challenge, wk5+6 days, mice were sacrificed to determine virus titers in different tissues (nasal turbinate, brain, lung, and kidney) and for histopathology. Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. Briefly, 100ng/well of RBD recombinant proteins (Abcam, UK) were coated overnight to the 96-well plates. The results should always be assessed in conjunction with patient . Laurent Kbaier, Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). Monoclonal anti-RBD (1:2,500), polyclonal-anti-S1 (1:5,000), -anti-S2 (1:5,000) or PSC (1:5,000) were used for detection of S protein in this step. Follow-up testing with a molecular diagnostic should be considered to rule out infection in these individuals. Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus. 4d). Article PubMed Many types of tests are used to detect SARS-CoV-2, 1 and their performance characteristics vary. . doi:10.1371/journal.pone.0281257, Editor: Deniz Can Guven, Elazg Fethi Sekin City Hospital: Elazig Fethi Sekin Sehir Hastanesi, TURKEY, Received: November 17, 2022; Accepted: January 18, 2023; Published: April 28, 2023. This study was performed using sera collected between October 2021 and December 2021 from a real life cohort of 69 individuals attending internal medicine and infectious diseases department of the European Hospital (Marseille). Prolonged Protective Immunity Induced by Mild SARS-CoV-2 Infection of K18-hACE2 Mice. The proprietary lipid and LNP composition are described in patent application WO2020097540A161,62. The OD450 of blanks were subtracted from OD450 of each sample before calculating antibody titer. This assay detects antibodies that block the interaction of SARS-CoV-2 with its entry receptor angiotensin-converting enzyme 2. Magnitude of asymptomatic COVID-19 cases throughout the course of infection: A systematic review and meta-analysis. SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) Kit (cPass) was purchased from Genscript (Piscataway, USA). A table of quantitative anti-spike levels for otherwise healthy, recently vaccinated individuals by week of vaccination to aid in interpretation of test results is available in Table 3 in this pre-print. JAMA Netw Open 4, e2137257 (2021). Indeed, cutoff values established using commercially available SARS CoV-2 diagnostic antibodies cannot represent a gold standard threshold value related to a level of neutralizing activity. The median values observed for the antibody binding assays were 143 BAU/ml (IQR 39748) for Abbott, 55 BAU/ml (IQR 19217) for Beckman, 636 BAU/ml (IQR 982369) for Roche, and 161 BAU/ml (IQR 32574) for Siemens, which demonstrated the variations between the assays (overall P < 0.0001). Nature 589, 603607 (2021). News-Medical. Cao, Y. et al. 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. Center of Excellence in Vaccine Research and Development (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Eakachai Prompetchara,Chutitorn Ketloy,Kittipan Tharakhet,Papatsara Kaewpang,Nongnaphat Yostrerat,Patrawadee Pitakpolrat,Supranee Buranapraditkun,Kanitha Patarakul,Teerasit Techawiwattanaboon,Tanapat Palaga&Kiat Ruxrungtham, Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Eakachai Prompetchara,Chutitorn Ketloy,Kittipan Tharakhet&Patrawadee Pitakpolrat, Integrated Frontier Biotechnology for Emerging Disease, Chulalongkorn University, Bangkok, 10330, Thailand, Eakachai Prompetchara,Chutitorn Ketloy,Kanitha Patarakul&Kiat Ruxrungtham, Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand, Suwimon Manopwisedjaroen&Arunee Thitithanyanont, Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand, Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, 10400, Thailand, Department of Veterinary Medicine, USAMD-AFRIMS, Bangkok, 10400, Thailand, BioNet-Asia, Co. Ltd, Bangkok, 10260, Thailand, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Kanitha Patarakul&Teerasit Techawiwattanaboon, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand, Genevant Sciences Corporation, Vancouver, BC, V5T 4T5, Canada, Department of Medicine, and School of Global Health, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, You can also search for this author in
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