Statistical significance was determined by two-sided MannWhitney tests. At this time-point, the NAb titers against both Omicron subvariants were still in the same level with week 5 titers (Fig. Moreover, the low dose regimen was also shown to induce a marked reduction in viral load in nasal turbinates, brain, and lung tissues compared to sham-treated controls. Nature 608, 593602 (2022). Chen, X. et al. 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. Beckman assay showed lower values as compared to all other assays (P< 0.008 for all paired comparisons); and lower values was observed for Siemens assay compared with Roche assay (P = 0.0033). Understanding the Role of Epigenetics in Cancer, Understanding Chronic Cough: Causes, Symptoms, and Diagnosis, Circumcised vs. Uncircumcised; Differences in the Penile Microbiome, Obesity management: a women's health approach, AI analysis software for Zebrafish you must know, Excessive digital technology use is associated with reduced sleep quality regardless of environmental and genetic factors, study finds, Activating well-being goals in grocery stores: innovative strategies for encouraging healthy food purchases. Body weight of ChulaCov19 vaccinated mice decreased slightly only at days 1 and 2 post-challenge then gradually increased to the same levels as pre-challenge at day 6 (Fig. Do ketogenic diets elevate low-density lipoprotein cholesterol levels? In this study, the S1 and S2 subunits of the spike protein . N Engl J Med 383, 26032615 (2020). Mol Ther Nucleic Acids 15, 2635 (2019). BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Here, we describe the construction and preclinical evaluation of mRNA expressing the ectodomain of native, prefusion-non-stabilized S protein of wild-type (WT) Wuhan-Hu1 strain encapsulated within lipid nanoparticles, henceforth referred to as ChulaCov19. (accessed May 01, 2023). Baiersdorfer, M. et al. Challenge study was conducted in ABSL-3 facility at AFRIMS, Bangkok, Thailand. They concluded that higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Tissues were collected at week 5+6 days for assessment of viral RNA. Ramasamy, M. N. et al. 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 As previously observed by Perkmann et al. Viral RNA was extracted from 140l serum and tissue samples using the QIAamp viral RNA mini kit (QIAGEN, Hilden, Germany). 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. Available from: https://www.who.int/initiatives/the-mrna-vaccine-technology-transfer-hub (2022). 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. These results reflect that ChulaCov19 was highly immunogenic and induced a Th1-skewed response in mice. The function of secreted S protein also determined whether it could bind to hACE-2. b hACE-2 binding assay (merged): culture supernatant collected from ChulaCov19 transfected cells incubated with HEK293T- hACE-2 cells. SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) Kit (cPass) was purchased from Genscript (Piscataway, USA). During the experiments, mice were maintained at 2022C and a relative humidity of 4510% on a 12h light/dark cycle. Lancet 397, 881891 (2021). More info. ChulaCov19 significantly enhanced the magnitude of both NAb and T cell responses compared to homologous 2-dose regimens of either CoronaVac or AZD1222. A Th2 dominant response following the vaccination remains a major concern of immunopathology that caused lung inflammation as reported in respiratory syncytial virus (RSV), SARS-CoV-1 and MERS-CoV42,43,44,45. COVID-19 CORONAVIRUS PANDEMIC [updated 19 August 2022; cited 2022 19 August 2022]. However, there was no discernible difference in burst activity between S1-treated and the control wells. Few studies have highlighted the lack of standardization of SARS-CoV-2 serology, despite the use of the international standards set by the World Health Organization (WHO) for SARS-CoV-2 immunoglobulin levels (BAU/ml) [1013]. PubMed PN20-06). By submitting a comment you agree to abide by our Terms and Community Guidelines. WHO. Science 368, 489493 (2020). Homologous prime/boost of each vaccine (CoronaVac, AZD1222, or ChulaCov19) were included as control groups. In brief, mouse splenocytes at 5105 cells/well were cultured with SARS-CoV-2 spike peptide pools spanning the entire sequence of spike protein, 25 peptides/pool (Mimotopes, Mulgrave, Victoria, Australia) at a final concentration of 2g/mL at 37C, 5% CO2 for 40h. Pools 15 and 610 corresponded to S1 and S2 regions of spike protein, respectively. 6b. At week 22, the psVNT-50 GMT for WT (Wuhan-Hu1), Delta (B.1.617.2), BA.1 and BA.4/5 were 25,539, 10,722, 2133, and 1707, respectively; 13-57 folds increase from the pre-boost baseline (Week18). When correlating protective efficacy and NAb titers induced by ChulaCov19, a micro-VNT50 titer of 2,560 before challenge in 1 g immunized mice was found to completely prevent viral burden in the lung as analyzed by ISH and RT-qPCR (Figs. Article e0281257. The S protein facilitates virus attachment and entrance into the host cell. Seventeen female K18-hACE2 mice (B6.Cg-Tg(K18-hACE2)2Prlmn/J), 7 weeks old (The Jackson Laboratory, Bar Harbor, ME, USA) were randomly divided into 3 groups. 199 0 obj <>stream Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice. The NAb titers were drastically enhanced after the second dose was given, p<0.01 for all dose ranges. 3b). All assays showed a high AUC for prediction of positive and negative results of Genscript sVNT (AUC > 0.90 for all) (Fig 2). 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. Lancet Microbe 2, e13e22 (2021). SARS-CoV-2 RNA-positive cells were examined and counted unblind by certified personnel. World Health Organization (2022). News-Medical. The overall concordance between antibody binding assays and the Genscript sVNT varied from 75% for Roche to 88% for Siemens (87% for Abbott and 78% for Beckman). Experiment 2: a prime/boost regimen of 5g of ChulaCov19 and 1/10 of human dosage of approved vaccines available during the study period, including viral-vectored (ChAdOx1; AZD1222, Lot A10062, Nonthaburi, Thailand) and inactivated (CoronaVac, Lot C202105081, Beijing, China) vaccines. A. Bloomberg. K18-hACE2 transgenic mice are highly susceptible and displayed clinical signs following SARS-CoV-2 challenge22,23. Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Therefore, during the surge of Omicron globally, there is a need of a boosting dose even with a first-generation vaccine or ideally with a second-generation vaccine such as a bivalent immunogen containing or encoding of Omicrons spike protein49,50. 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 . 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. 1b). RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge. Current SARS-CoV-2 antibody tests detect IgM or IgG to viral spike or nucleocapsid proteins. These authors jointly supervised this work: Drew Weissman, Kiat Ruxrungtham. Spin within 24 hours and prior to shipment. S-specific total IgG analyzed at week 2 revealed that all ChulaCov19-immunized mice, either with 1 or 2 doses, elicited anti-S-specific IgG response from the lowest dose of 0.2g with a dose-dependent response pattern. 2c). The total volume of 50l of viral RNA was obtained from each sample. Samples from 69 patients were analyzed. Google Scholar. PubMed Spencer, A. J. et al. 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). Biomedicines 10, 1464 (2022). This candidate vaccine has now completed non-clinical toxicity and biodistribution studies and has entered Phase 1 and 2 human trials. Previous studies reported that low-dose vaccination induced only high avidity T cells. For the Siemens assay, the optimal cutoff was within the same range as the reference cutoff (270 BAU/ml). Supernatant collected from transfected cell was incubated with HEK293T-hACE-2 at 37 oC for 1h then washed twice with PBS. van Doremalen, N. et al. ROC curves for each antibody binding assay according to Genscript sVNT. Stanislas Rebaudet, The ChulaCov19 vaccine development program has exactly this goal, striving to address the current and future pandemics in LMICs54. Similar findings were also observed in BA.4/5 subvariant (Fig. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. J Exp Med 184, 485492 (1996). The presence of three SARS-CoV-2 genes (ORF1ab, nucleocapsid protein (N), and spike protein (S)) was identified using real-time PCR with the TaqPath RT-PCR COVID-19 kit (Thermo Fisher Scientific . The results resembled those observed in the panel that used a commercial recombinant S-trimer instead of transfected supernatant. 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. For full functionality of this site, please enable JavaScript. 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 . In the control group, positive viral RNA staining was present in individual neurons of the olfactory bulb (4/4), epithelial cells of the nasal sinus (4/5), alveolar epithelial cells and macrophages in the lung (5/5), see Table1. The RNAscope ISH assay was performed using an RNAscope 2.5 HD Red Detection Kit (ACD, 322372) as followed. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. 4b). UW MedicineDepartment of Laboratory MedicineVirology- Covid Testing Lab1601 Lind Ave SWRenton, WA 980573356Tel: (206) 685-6656 opt 4. Unfortunately, it has also been proven that vaccine efficacy decreases over time14. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Zhang, N. N. et al. Moreover, anamnestic NAb response is undetectable in challenge animals. 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]. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or boost vaccination and has entered clinical development. News-Medical. Google Scholar. The spike (S) protein of the virus, which contains the major neutralizing epitopes in the receptor binding domain (RBD) and N-terminal domain (NTD), has proven to be the most promising immunogen18. 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). The data supporting the findings of this work are available within the paper and in the Supplementary Information file. Ying, B. 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 titers were determined in duplicate assays from 5 mice in each group. Pharmaceutics 14, 1427 (2022). Qualitative and semi-quantitative detection of antibodies to SARS-CoV-2 spike protein receptor binding domain (RBD). Medicines and Healthcare products Regulatory Agency (2022). Having more antibodies means your body can fight infection better than having fewer antibodies. and JavaScript. 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. Notably, SARS-CoV-2 RNA measured by ISH was undetected in lung tissues in mice vaccinated with ChulaCov19 at either 1 or 10 g dose. Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. S-specific IgG measurement was performed employing indirect ELISA as described previously56,67. The vaccine was measured for its immunogenicity in BALB/c mice both using ChulaCov19 alone or as heterologous prime/boost regimens alongside the approved vaccines (Fig. Statistical significance was determined by two-sided MannWhitney test. Meanwhile, psVNT50 against BA.4/5 subvariant showed the lowest GMT in 1, 10, and 30g dosed groups. After SARS-CoV-2 challenge, there was no measurable decline in body weight among vaccinated groups. SD; standard deviation. These common antibody tests use purified proteins of SARS-CoV-2 (not a live virus) to detect the presence of binding antibodies that attach to a virus, per the CDC. Immunogenicity and Safety of ChulaCov19 BNA159 Vaccine as a Booster Dose in Adults). According to French regulations, the study was approved by the French ethics committee (Health Data Hub, approval number: F20211217094518). Tseng, C. T. et al. Thank you for visiting nature.com. Bar-On, L. et al. 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. Stability: Sample stable off the clot, red blood cells, or separator gel for 7 days at 2-8C. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. Differences were considered significant at p<0.05 with exact p-values shown. Interestingly, the 3rd dose of ChulaCov19 administered at 17-week apart significantly boosted the NAb against all variants analyzed. Philippe Cartlamy, Laboratoire AlphabioBiogroup, Marseille, France, Affiliation: These factors might make it difficult to draw a strong conclusion on vaccine efficacy from the current of experiments. 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. 4c. While most serologic assays are qualitative, a quantitative serologic . When considering specific optimal cutoffs, agreement between each antibody binding assay and Genscript sVNT increased consistently from 0.03 units for the Siemens assay to 0.25 units for the Beckman assay (kappa = 0.79 and 0.77, respectively). 6a). Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines. However, this was still far lower than using homologous ChulaCov19 or AZD1222-prime/ChulaCov19-boost immunization regimens (Fig. Source data are provided as a source data file. We recommend outside providers arrange to have their patients' blood drawn at their usual clinical draw sites and sent to the lab, preferably after contacting Client Support Services at commserv@uw.edu to facilitate testing. Is there an association between the consumption of ultra-processed food and adverse microbiota-gut-brain axis implications? In contrast, a higher dose vaccination not only induced the mixture of low and high avidity T cells responses, but also induced the clonal deletion of high avidity CD8 T cells29,30,31. Google Scholar. N Engl J Med 383, 24392450 (2020). Nat Commun 11, 6013 (2020). & Liu, J. Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review. Gilles Antoniotti, To obtain After the first dose, NAb were detected in mice that received 1, 10, and 30g ChulaCov19 with corresponding GMTs of micro-VNT50 titer of 80, 368, and 735, respectively. After 1h incubation at 37C, plates were washed vigorously with washing buffer (PBS+0.5% Tween 20, PBST). Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Previous study by Eichinger KM, et al. Get the most important science stories of the day, free in your inbox. Please note that medical information found PubMed Central Among the 1g group, only one tissue had very few positive cells, the nasal epithelium. The 5-fold serially diluted mice sera were added in duplicate. Two approved mRNA vaccines, ComirnatyTM by Pfizer/BioNTech and SpikevaxTM by Moderna, comprise 2 proline substitutions at residues 986 and 987 of the S-protein (known as S-2P) to stabilize the prefusion conformational structure. Nature Communications (Nat Commun) 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. In the latter VNT protocol, serum-virus mixtures were incubated in VERO E6 cells for 5 days. Peletta, A. et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. All authors reviewed the results and approved the final version of the manuscript. In contrast, sham-treated animals failed to show any NAb response except for one animal on Wk5+6d (Fig. Negative test results do not rule out the possibility of an infection with SARS-CoV-2. The investigators strictly adhered to the principles and guidelines of the Institute of Animals for Scientific Purposes Development, National Research Council of Thailand. This demonstrated the significant protective efficacy of ChulaCov19 in the preclinical phase. It was also evaluated for the protective efficacy in transgenic mice expressing human angiotensin-converting enzyme-2 (ACE2), Fig. Bars represent the GMTs and 95% CI for each group. At 24hr post-transfection, both intracellular and secreted S protein expressions were analyzed. The S1 subunit interacts with the angiotensin-converting enzyme 2 (ACE2) receptor present in the intestinal and lung cells. The overall concordance between the antibody binding assays and the Genscript sVNT also increased consistently i.e., 11% increase for Roche (86% concordance), 10% increase for Beckman (88% concordance), 2% increase for Siemens (90% concordance), and 1% increase for the Abbott assay (88% concordance). The S1 subunit substantially lowered the number of bursts per electrode, whereas the S2 subunit did not exhibit the same degree of reduction. "Neurological phenotypes induced by SARS-CoV-2 spike protein in neurons". Translating a Thin-Film Rehydration Method to Microfluidics for the Preparation of a SARS-CoV-2 DNA Vaccine: When Manufacturing Method Matters. KR, DW, MGA, CK, EP, and SB are co-inventors of the submitted ChulaCov19 mRNA vaccines Patent. The reaction was stopped by adding 50l/well of 0.5M sulfuric acid. S-specific IFN- positive T cells were determined in duplicate assays from 5 mice in each group. J. Clin. To date, few studies have defined correlates of protection against SARS-CoV-2 infection that can be used by regulators and vaccine developers. Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine. PLOS ONE promises fair, rigorous peer review, T-cell responses to SARS-CoV-2 can be indirectly tested with antigen tests (such as Elispot) that tests for cytokines produced (i.e. For western blot analysis, cell culture supernatant was analyzed by 12% polyacrylamide gel then transferred onto nitrocellulose membrane. Detection of antibodies to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances detection of infection There were few limitations in this study. Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. The mRNA was transcribed to contain 101 nucleotide of adenine (101-poly(A) tails). Boxplots for each antibody binding assay according to Genscript sVNT positive and negative results. N Engl J Med 384, 403416 (2021). Samples from 69 patients were included in this study. The absorbance was measured at a wavelength of 450nm using a Varioskan microplate reader (ThermoFisher Scientific, Vantaa, Finland). PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US. Characteristics like the number of bursts per electrode, their duration, frequency, and the number of spikes per burst according to the treatment condition were also quantified. Discover a faster, simpler path to publishing in a high-quality journal. https://ClinicalTrials.gov/show/NCT05605470 (2022). The procedure of mouse IFN- ELISPOT used in this study was described in our previous reports56,72. Some tests provide results rapidly (within minutes); others require 1-3 days for processing. By Day 4 after challenge, two mice in PBS-receiving group (control) began to show clinical signs of anorexia, lethargy, and rough hair coat. Median time between last vaccination and sampling was 5.2 months (3.16.4). 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. A positive result means your body's immune system has generated a response to the COVID-19 vaccine. The authors would like to thanks Dr.Navapon Techakriengkrai, Faculty of Veterinary Science, Chulalongkorn University for providing HEK293T-hACE-2 cells. 1a). The use of antibody therapy for PrEP, which is the use of medications to prevent infection before exposure to a virus, is currently being studied for its potential efficacy in immunocompromised individuals with COVID-19. Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Comparing the clinical efficacy of COVID-19 vaccines: a systematic review and network meta-analysis. 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). Sci. Safety and Immunogenicity of ChulaCov19 BNA159 mRNA Vaccine.). Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, AlphabioBiogroup). This implies that ChulaCov19 could induce a long-lasting NAb, at least until 15 weeks postimmunization especially against WT (Wuhan-Hu1) and Delta (B.1.617.2) variants. First bivalent COVID-19 booster vaccine approved by UK medicines regulator). The team then performed a rescue experiment to ascertain if this neuronal phenotype is reversible. Eichinger, K. M. et al. Omicron stood out from other variants because it contained mutations that helped it evade immune cell protection. 200 0 obj <>]/Filter/FlateDecode/BitsPerComponent 8/Length 2211/Height 275>>stream Copyright and Disclaimer, Department of Laboratory Medicine & Pathology, COVID-19 Testing Frequently Asked Questions For Patients, Frequently Asked Questions About COVID-19 Testing for Providers & Clients. Virus titers were quantified by RT-qPCR and by determined the log10TCID50 values. Proc Natl Acad Sci U S A 93, 41024107 (1996). Additional group (Experiment 3) immunized with 5g of ChulaCov19 was included for evaluation of NAb durability as measured at week 18 (15 weeks after received the 2nd dose) and the boosting effect of 3rd ChulaCov19 dose administered at week 20. 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). Kappa increased to 0.76 for the Abbott assay (0.04 units increase) and to 0.71 for the Roche assay (0.19-unit increase). The Abbott SARS-CoV-2 IgG immunoassay detects antibodies to the viral nucleocapsid protein (NP). Koonpaew, S. et al. Zhang, L. et al. Ann Intern Med 174, 286287 (2021). Mid-point titers were calculated and expressed as the reciprocals of the dilution that showed an optical density (OD) at 50% of the maximum value substracted with the background (BSA plus secondary antibody). ISSN 2041-1723 (online). Such unusual characteristics, in conjunction with a highly contagious profile, resulted in the rapid spreading of the virus worldwide. Background Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. Cell 182, 5058.e58 (2020). The average decline from peak to euthanasia among PBS-receiving mice was 17%. Available from: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants (2022). Posted in: Medical Science News | Medical Research News | Disease/Infection News, Tags: ACE2, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Blood, Blood Pressure, Brain, Cell, Coronavirus, Coronavirus Disease COVID-19, covid-19, Electrode, Enzyme, Frequency, Membrane, micro, Neurons, Newborn, Phenotype, Protein, Receptor, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine, Virus. Source data are provided as a Source Data file. The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). 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. SD; standard deviation. 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. The interpretation of the calculated ratios was performed as manufacturer's recommendation. van Doremalen, N. et al. 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. p<0.05 and p<0.01 are indicated by * and **, respectively. They were widely available in these countries for approximately a year before being accessible on other continents. 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. The vaccine inequity issue is a huge challenge to healthcare in LMICs. Five microliters of each RNA sample was used in quantitative RT-PCR that was performed using CDC procedure73 and AFRIMS SOPs in vitro SARS-CoV-2 RNA transcripts (IVTs). 6c. 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. 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. 2a). Retrieved on May 01, 2023 from https://www.news-medical.net/news/20230427/Neurological-phenotypes-induced-by-SARS-CoV-2-spike-protein-in-neurons.aspx. Agrawal, A. S. et al. )5ul~eC}=,t?~]r6T5\OQhyN=8. You should not interpret the results of this test as an indication or degree of immunity or Currently there are at least 11 approved vaccines using various technology platforms, including mRNA, inactivated virus, viral-vector and recombinant protein10. Funding: The author(s) received no specific funding for this work.