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a Kinetics of total IgG at 2 weeks after receiving 1 or 2 doses of 0.2, 1, 10, and 30g of ChulaCov19. 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. As with many viral respiratory infections, knowledge of the immune response to SARS-CoV-2 after a natural infection or vaccination, that could be predictive of the protection conferred, is challenging and not well established [14]. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. Median time between last vaccination and sampling was 5.2 months (3.16.4). IgG2a and IgG1 subclasses were also assessed to determine Th1 and Th2 responses, respectively. A. In response to the COVID19 pandemic and in preparation for future pandemics, Thailand has funded this mRNA vaccine development program from preclinical to manufacturing and clinical development. To date, few studies have defined correlates of protection against SARS-CoV-2 infection that can be used by regulators and vaccine developers. van Doremalen, N. et al. The total volume of 50l of viral RNA was obtained from each sample. [ view less ], Affiliations: on this website is designed to support, not to replace the relationship The objective of the present study was to establish a new optimal threshold of protection for four different SARS-CoV-2 antibody assays [14]. 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]. Note; the IgG2a/IgG1 ratio of 10g and 30g immunized mice were not analyzed due to limited volume of serum samples. 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. These tests should not be used to diagnosis or exclude acute SARS-CoV-2 infection. COVID19 Vaccine Tracker [cited 2022 19 August]. PubMed Central More info. Google Scholar. p<0.05 and p<0.01 are indicated by * and **, respectively. Kunkalikar, Bhavana. For example, the psVNT-50 against BA.1 in the CoronaVac-prime/ChulaCov19-boost group (psVNT-50 GMT=875) was significantly higher (p<0.01) than homologous CoronaVac (psVNT-50 GMT=5.1) and homologous AZD1222 (psVNT-50 GMT=2.7) groups. Nat Commun 13, 4610 (2022). 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 . Detailed amino sequence was shown in Supplementary File1. https://doi.org/10.1038/s41467-023-37795-0, DOI: https://doi.org/10.1038/s41467-023-37795-0. It was also evaluated for the protective efficacy in transgenic mice expressing human angiotensin-converting enzyme-2 (ACE2), Fig. At 2 weeks after the second immunization, mice were challenged intranasally with 2104 pfu (in 50L) of SARS-CoV-2 (wild-type). 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). In many countries, immunization regimens have frequently employed mixtures of different vaccine platforms (also known as a heterologous prime-boost). JAMA Netw Open 4, e2137257 (2021). van Doremalen, N. et al. However, it has not been shown that COVID-19 mRNA vaccine encoding non-stabilized spike protein is not immunogenic or is not protective against viral challenge. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Results are reported as AU/mL. Splenocytes were collected at 2 weeks after the second dose (Experiment 1 & 2). Baseline characteristics are shown in Table 1. A positive test result with the SARS -CoV-2 antibody test indicates that antibodies to SARS -CoV-2 were detected, and the individual has potential ly been exposed to Experiment 2: c micro-VNT50 titers against WT (Wuhan-Hu1), Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) live-virus at two weeks after receiving various homologous or heterologous prime/boost regimens. Quantitative Measurement of Anti-SARS-CoV-2 Antibodies: Analytical and Article Cell 182, 5058.e58 (2020). Bleeding was performed at 2 weeks following each dose (and at week 18 for Experiment 3). Funding: The author(s) received no specific funding for this work. Performance of nucleocapsid and spike-based SARS-CoV-2 serologic assays In summary, this mRNA vaccine development is an effort to set up the technology platform in LMICS. J Immunol 166, 16901697 (2001). 2b). SARS CoV 2 Spike Antibody, IgG After 2-dose, the GMTs of micro-VNT50 titer for 0.2, 1, 10, and 30g were 1280, 11,763, 54,047, and 62,084, respectively (Fig. Is there an association between the consumption of ultra-processed food and adverse microbiota-gut-brain axis implications? A threshold of 20% was used for positivity. 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. COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Safety and Immunogenicity of ChulaCov19 BNA159 mRNA Vaccine.). Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19). In supernatant, we could detect both intact S and cleaved S1 and S2 (Fig. The team then performed a rescue experiment to ascertain if this neuronal phenotype is reversible. https://apps.who.int/iris/handle/10665/363344 (2022). 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). For patients who do not regularly seek care within UW Medicine, our phlebotomists at the University of Washington Medical Center-Northwest Campus (UWMC-NW) and UWMC-NW Outpatient Medical Center (OPMC) located on Meridian Ave. N. are able to perform blood draws for testing with a valid provider order. Figures were created with BioRender.com. et al. Overview of Testing for SARS-CoV-2, the virus that causes COVID-19 SARS2Mutant: SARS-CoV-2 amino-acid mutation atlas database In this episode of omg OMx, Bruker's science-driven podcast, Kate Stumpo interviews Daniel Hornburg, the VP of Proteomics at Seer, as they discuss the innovative technologies in plasma proteomics. A recent randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine conducted in more than 8,500 patients in the United Kingdom, analyzed the antibody levels associated with protection against SARS-CoV-2 [7]. Cellular and humoral responses after second and third SARS-CoV-2 All isolates were quantitated by tissue culture infectious dose TCID50 using the Reed-Muench method. Agreement between the antibody binding assays and the Genscript sVNT assay is shown in Table 2. Peletta, A. et al. Folegatti, P. M. et al. When considering a reference cutoff of 264 BAU/ml, the assays showed moderate to good agreement with Genscript sVNT, with strong variations of the kappa index from 0.52 for Beckman and Roche to 0.76 for Siemens (kappa = 0.72 for Abbott). Cells with approximately 8090% confluency were transfected with 1g of IVT ChulaCov19 using Lipofectamine MessengerMax (Invitrogen, Carlsbad, CA, USA) according to the manufacturer protocols. On the contrary, low avidity T cells which require a higher amount of viral antigen were able to lyse the viral infection after the new virion were produced31. If testing will be delayed more than 7 days store at -20C or colder. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in a credit line to the material. Together with the emergence of new VOCs, a booster dose (either homologous or heterologous vaccine modality) is required to enhance the vaccine effectiveness15. Med. 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. 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). 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). Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). For the Siemens assay, the optimal cutoff was within the same range as the reference cutoff (270 BAU/ml). Bhavana Kunkalikar is a medical writer based in Goa, India. Zhang, L. et al. Qualitative and semi-quantitative detection of antibodies to SARS-CoV-2 spike protein receptor binding domain (RBD). For example, the micro-VNT50 GMT against WT (Wuhan-Hu1) in the AZD1222-prime/ChulaCov19-boost group was 7-fold higher than 2-dose AZD1222 immunization (GMT of micro-VNT50 were 31,042 vs 4457, p=0.0079). CAS Vacharathit, V. et al. 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. Prompetchara, E. et al. *:;eOmU3vNf]l|*,xH_%81j%/d}z(t|oSqRn!%vD(?+&jnwSzs-*"d/u7m4?zz &T/nzw4W-[mxST rEG"7$]d**UfX %7[{ c!ew-( The neurons were treated with similar S1 concentrations on day 12. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in 6 (60%) and 8 (80%) patients, respectively. 4d). Interferon gamma) in response to SARS-CoV-2 antigens (M, N, S peptides). The assay is an electrochemiluminescent. 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. : draft manuscript preparation. (2023, April 27). ISSN 2041-1723 (online). SD; standard deviation. Laurent Chiche, In the latter VNT protocol, serum-virus mixtures were incubated in VERO E6 cells for 5 days. PN20-06). 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 . Ma, Q. et al. However, there was no discernible difference in burst activity between S1-treated and the control wells. Immune Response to SARS-CoV-2 Vaccines. KL and JH are employees of Genevant Sciences Corporation and are named on patent describing lipid nanoparticles. mSphere 7, e0024322 (2022). Buschmann, M. D. et al. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 1b. 200 0 obj <>]/Filter/FlateDecode/BitsPerComponent 8/Length 2211/Height 275>>stream The threshold or cutoff value for immunity in immunocompromised individuals in relation to COVID-19 is currently not well established. By Day 4 after challenge, two mice in PBS-receiving group (control) began to show clinical signs of anorexia, lethargy, and rough hair coat. Meta-analysis shows phytosterol-fortified foods effectively lower LDL cholesterol levels. SARS-CoV-2 delta variant infection in domestic dogs and cats, Thailand. The reaction was stopped by adding 50l/well of 0.5M sulfuric acid. All studies were conducted under protocols approved by the Committees on Care of Laboratory Animal Faculty of Medicine, Chulalongkorn University (IACUC approval no. Nature 589, 603607 (2021). Developing highly effective vaccine platforms like mRNA technology in low- and middle-income countries (LMICs) is therefore an important goal21. 1a). This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. Helmy, Y. 6a). At this time-point, 10g dosed mice induced significantly higher in GMTs of micro-VNT50 titers than 1g dosed mice (p=0.0065). To address dose-response study of the ChulaCov19 and heterologous prime-boost responses with other approved COVID-19 vaccines, female BALB/c mice (Mus musculus), 4-6 weeks of age, (procured from Nomura Siam International, Bangkok, Thailand) were randomly divided into 5 mice/group for 3 sets of experiment. The vaccine inequity issue is a huge challenge to healthcare in LMICs. Viral RNA was extracted from 140l serum and tissue samples using the QIAamp viral RNA mini kit (QIAGEN, Hilden, Germany). At 24hr post-transfection, both intracellular and secreted S protein expressions were analyzed. You are using a browser version with limited support for CSS. % Source data are provided as a source data file. Having more antibodies means your body can fight infection better than having fewer antibodies. Study: SARS-CoV-2 Spike Protein Reduces Burst Activities in Neurons Measured by Micro-Electrode Arrays. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 - PLOS However, harmonization of neutralizing antibody titers is necessary to determine a common threshold using which vaccine protection can be predicted. Since the outbreak of COVID-19, the world has raced to understand and accurately diagnose infection caused by SARS-CoV-2. 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. Oran, D. P. & Topol, E. J. Schematic view of the SARS-CoV-2 particles, genome arrangement, and proteome organization. Some must be performed in a laboratory by trained personnel, some can be performed at the point of care, and others can be . Indeed, the BAU/ml values were performed only on the B.1.1.7 variant in neutralization assays and not on different strains of the virus; hence, there may be no relation between immune markers and disease outcome [7]. Comparisons of the data between groups were made using non-parametric tests (MannWhitney test). a-0ZG{Px(rA![|-Ml0(9ELO_>+Rf_I4!=fuPq^$\1$j/ Further investigation using different techniques, such as viral isolation and titration from the collected tissues is required to draw a definite conclusion. 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. 2a). 5b). 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). Bars (a) or horizontal lines (b) represent the geometric mean (GMT) for each group while error bars indicate the 95% confident interval. 4c. Four antibody binding assays were used for serological testing according to the instructions of the manufacturer. Agreements between antibody-binding assays and Genscript sVNT were performed using Cohens kappa, crude concordance rate, and area under curve (AUC). Even as SARS-CoV-2 mutates, some human antibo | EurekAlert! The female/male ratio was 67/33, and the median age was 47 years (IQR 3463). 6b, c, Table1). Meanwhile, psVNT50 against BA.4/5 subvariant showed the lowest GMT in 1, 10, and 30g dosed groups. The data as well as the p values suggested that the anti-S1 antibody reversed the impact of S1 on bursting activities. Cell nuclei were counter stained with 4, 6-diamino-2-phenylindole hydrochloride (DAPI) (Sigma-Aldrich, USA). This would allow for identification of the corresponding thresholds, using high-throughput binding antibody assays. The WHO International Standard for COVID-19 serological tests: towards CAS Splenocytes from mice immunized with various dosages of ChulaCov19 (Experiment 1) were analyzed as summed frequency of S-specific IFN- positive T cells (Fig. There were no anamnestic responses (four-fold increase on micro-VNT50 titers) in all vaccinated groups 6 days after the challenge, whereas one mouse in the control group developed a low micro-VNT50 titer at 40. a Kinetic response of micro-VNT50 titer after ChulaCov19 immunization and after challenge. Ying, B. et al. e0281257. mRNA encapsulation was performed by Genevant Sciences Corporation (Vancouver, British Columbia, Canada). Provided by the Springer Nature SharedIt content-sharing initiative. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Results from antibody testing should not be used as the sole basis to diagnose or exclude SARS-CoV-2 infection or to inform infection status. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. Cell 185, 24222433.e2413 (2022). Int J Infect Dis 112, 227234 (2021). Here we demonstrated that an LNP-encapsulated mRNA encoding a secreted form of prefusion nonstabilized ectodomain of SARS-CoV-2 spike protein ChulaCov19 was able to elicit robust, specific antibody and T-cell responses. This result implied that the decrease in Nab titers against BA.4/5 may be improved with higher mRNA vaccine doses. The 4-week gap was used according to the preclinical study protocol of ChAdOX-vectored vaccines65,66. 6c) may be due to RT-qPCR, a highly sensitive method detecting the free viral RNA from disintegrated virus. Currently there are at least 11 approved vaccines using various technology platforms, including mRNA, inactivated virus, viral-vector and recombinant protein10. Available from: https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution (2022). Front Cell Infect Microbiol 11, 781429 (2021). Moreover, the tissue slides were examined unblind. 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. RNA copies were calculated as genomic equivalent/mg of tissue. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). Nature 608, 593602 (2022). Roche Diagnostics, Inc. - Elecsys Anti-SARS-CoV-2 S. This test detects human SARS-CoV-2 antibodies . Moreover, all five mice in control group exhibited varying symptoms of increased anorexia, lethargy, immobility, rough hair coat and increased respiration rate and effort. Stability: Sample stable off the clot, red blood cells, or separator gel for 7 days at 2-8C. b heterologous prime/boost study; mice were primed with CoronaVac or AZD1222 vaccine and boosted with ChulaCov19 (5g). 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. Calculations were performed using the SAS V9.4 software (SAS Institute Inc., Cary, NC, USA). 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