b heterologous prime/boost study; mice were primed with CoronaVac or AZD1222 vaccine and boosted with ChulaCov19 (5g). 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. Google Scholar. 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. For western blot analysis, cell culture supernatant was analyzed by 12% polyacrylamide gel then transferred onto nitrocellulose membrane. 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. The Euroimmun Anti-SARS-CoV-2 IgG and IgA tests are separate ELISAs that detect antibodies against the S1 subunit of the SARS-CoV-2 spike protein. The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies. Splenocytes from mice immunized with various dosages of ChulaCov19 (Experiment 1) were analyzed as summed frequency of S-specific IFN- positive T cells (Fig. The investigators strictly adhered to the principles and guidelines of the Institute of Animals for Scientific Purposes Development, National Research Council of Thailand. Moreover, the feasibility of large-scale production as well as rapid adaptability to new variants are major advantages of the mRNA production platform. The particles were re-characterized at 6- and 12-month after manufacture for stability assessment. Lancet 396, 467478 (2020). 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. Statistical significance was set at P < 0.05. demonstrated that only Th2-dominant but not Th1/Th2 balanced response enhanced lung pathology in adjuvanted recombinant RSV immunized mice45. Using the Youden index maximization approach, optimal cutoffs were consistently lower than the reference cutoff of 264 BAU/ml for the Abbott and Beckman assays (148 and 48 BAU/ml, respectively). Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Funding: The author(s) received no specific funding for this work. A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19). In contrast, mice that received 2 doses of either 1 or 10 g of ChulaCov19 were normal with no symptoms throughout postchallenge period of 6 days. Stability: Sample stable off the clot, red blood cells, or separator gel for 7 days at 2-8C. Samples from 69 patients were analyzed. Source data are provided as a Source Data file. Prevalence of Asymptomatic SARS-CoV-2 Infection. Results are reported as AU/mL. p<0.05 and p<0.01 are indicated by * and **, respectively. Walsh, E. E. et al. 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. Increasing evidence suggests that vaccination regimens for COVID-19, that are applied to the general population, do not adequately protect a significant proportion of immunocompromised patients [5,6]. Agreement between antibody binding assays and Genscript sVNT positive and negative results according to the reference cutoff (264 BAU/ml). : study conception and design, E.P., K.T., and C.K. N Engl J Med 383, 19201931 (2020). Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens. SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) Kit (cPass) was purchased from Genscript (Piscataway, USA). a-0ZG{Px(rA![|-Ml0(9ELO_>+Rf_I4!=fuPq^$\1$j/ Comparable to the S1 data, the team identified a significant reduction in surge activities. The outcome strongly suggests that the RBD itself is sufficient to suppress surge activities. Vero E6, green monkey kidney epithelial cell line, was obtained from ATCC (Old Town Manassas, VA, USA). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. They concluded that higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. Nature 589, 603607 (2021). 3b). 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. Hum Vaccin Immunother 12, 23512356 (2016). Mice sera were further analyzed for NAb by psVNT50 test against the important recent VOCs, including Delta (B.1.617.2) variant and Omicron (BA.1 and BA.4/5) variants, and titers significantly decreased for all VOCs. Helmy, Y. 7, eabi5246 (2021). KL and JH are employees of Genevant Sciences Corporation and are named on patent describing lipid nanoparticles. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). RNA copies were calculated as genomic equivalent/mg of tissue. Study: SARS-CoV-2 Spike Protein Reduces Burst Activities in Neurons Measured by Micro-Electrode Arrays. 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. This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. This finding implied that ChulaCov19 is highly immunogenic against WT (Wuhan-Hu1) strain. Contact: commserv@uw.edu | {KnXEW;>2THg_J}iX,n7 UndO'%vh9(WG(Rf&oKnn>*&j6$79^*G$73sxv_7$wWfbgD7l7`{ FD5`yK]TS.t0 bM/.<1~ Na RUL6>lnn;P"_1m^ Differences were considered significant at p<0.05 with exact p-values shown. Samples from 69 patients were included in this study. IgG2a and IgG1 subclasses were also assessed to determine Th1 and Th2 responses, respectively. The team also determined whether the S1 subunit influences mature neurons during cell exposure. In the control group, 3 out of 5 mice reached euthanasia criteria on Day 5 hence only 2 mice were analyzed for body weight on Day 6 after challenge. In the challenge study, NAb was also assessed by live-virus microneutralization test against strain hCoV-19/Hongkong/VM20001061/2020 with slightly different incubation period and detection technique. In this study, the S1 and S2 subunits of the spike protein . The second dose of ChulaCov19 strongly augmented the IgG antibody levels with an increase of 10-19 folds, p<0.01 for all dose ranges (Fig. Eichinger, K. M. et al. Ma, Q. et al. Vaccines (Basel) 9, 850 (2021). Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. sample is stable for 7 days at 2-8C once separated from a clot or red blood cells, or in a gel separator tube. Virus titers were quantified by RT-qPCR and by determined the log10TCID50 values. PubMed Whether differences in response impact vaccine efficacy needs further study. How are the results reported for the anti-nucleocapsid antibody test, and what is the clinical significance? The 4-week gap was used according to the preclinical study protocol of ChAdOX-vectored vaccines65,66. 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. Follow-up testing with a molecular diagnostic should be considered to rule out infection in these individuals. From nanoparticle-based enrichment to mass spec refinements, they explore how these tools facilitate unbiased, deep, and rapid proteomics. Infect Dis Poverty 11, 53 (2022). 2023. This assay detects antibodies that block the interaction of SARS-CoV-2 with its entry receptor angiotensin-converting enzyme 2. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Of note, at week 5, all vaccinated mice at the 10 g dose, and 5 of 6 mice at 1 g dose elicited SARS-CoV-2 specific serum IgA (supplementary FigureS1a and S1b). First bivalent COVID-19 booster vaccine approved by UK medicines regulator). Get the most important science stories of the day, free in your inbox. Bellamkonda, N. et al. PubMed 2b). The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical. In-depth investigation of viral burden in different tissues as well as T cells quality induced by various vaccine dosages are still required. 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. 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). 399, 924944 (2022). 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. Proc Natl Acad Sci U S A 93, 41024107 (1996). Nature 586, 578582 (2020). Proc Natl Acad Sci U S A 114, E7348E7357 (2017). UW MedicineDepartment of Laboratory MedicineVirology- Covid Testing Lab1601 Lind Ave SWRenton, WA 980573356Tel: (206) 685-6656 opt 4. 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. Testing for SARS-CoV-2 Infection. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. To obtain Available from: https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution (2022). 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. Peletta, A. et al. KR, DW, MGA, CK, EP, and SB are co-inventors of the submitted ChulaCov19 mRNA vaccines Patent. They were widely available in these countries for approximately a year before being accessible on other continents. Sylvie Jordana, 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. S-specific IgG measurement was performed employing indirect ELISA as described previously56,67. ];V^srE]DwCyTPre_fyG;Cb@*\d$ j '-|,!]jF/J9r\s%3! Labcorp test details for SARS-CoV-2 Semi-Quantitative Total Antibody, Spike . Competing interests: The authors have declared that no competing interests exist. 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. ADS 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. Thus, most recently approved vaccines employ full-length S (with or without modification) or whole virus (inactivated) as a target antigen19. Please use one of the following formats to cite this article in your essay, paper or report: Kunkalikar, Bhavana. 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). Previous studies reported that low-dose vaccination induced only high avidity T cells. mSphere 7, e0024322 (2022). 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. Statistical significance was determined by two-sided MannWhitney test. 6b. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Omicron stood out from other variants because it contained mutations that helped it evade immune cell protection. ISSN 2041-1723 (online). 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. 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]. 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. In vaccinated people: In the homologous prime/boost of these 2 approved vaccines groups, each was given at four weeks interval. The analysis of the responses to different parts of S-specific pool peptides in all vaccinated groups showed that peptide pool #3-5 (which include receptor-binding domain or RBD) and pool #9 (which includes Heptad Repeat 2 or HR2) in S1 and S2, respectively, were the most common peptides pools recognized by the vaccinated mice T-cells. No significant difference among agreements was observed. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Oran, D. P. & Topol, E. J. As previously observed by Perkmann et al. 4d). Koonpaew, S. et al. 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. 3b). However, further beneficial evaluation on the use of native-like S protein structure requires in-depth analysis in clinical settings especially in immune elicitation characteristics. More importantly, in partnering with a domestic vaccine manufacture, BioNet Asia, ChulaCov19 can now be manufactured and formulated locally54. 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). An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. Goat-anti-mouse IgG-FITC, donkey-anti-rabbit IgG-FITC (both were from BioLegend, CA, USA) or goat-anti-human AlexaFluor647 (Southern Biotech, AL, USA), at dilution of 1:5,000 was used as secondary antibodies following anti-RBD, -S1, -S2 or PCS staining. d psVNT50 NAb titer results at two weeks after the second dose in various prime/boost regimens againt Omicron BA.1 and BA.4/5 subvariants. 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. 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. Statistical significance was determined by two-sided MannWhitney test. T-cell responses to SARS-CoV-2 can be indirectly tested with antigen tests (such as Elispot) that tests for cytokines produced (i.e. 199 0 obj <>stream Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. PubMed Li, R. et al. The purified mRNA-S (ChulaCov19) with undetectable endotoxin was tested for protein expression in VERO E6 cells. Lancet Microbe 2, e13e22 (2021). For the heterologous prime/boost, mice primed with CoronaVac or AZD1222 and then boosted with ChulaCov19 generated significantly higher GMT against WT (Wuhan-Hu1), Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.529) when compared to the respective homologous prime/boost groups. "Neurological phenotypes induced by SARS-CoV-2 spike protein in neurons". Article Note; the IgG2a/IgG1 ratio of 10g and 30g immunized mice were not analyzed due to limited volume of serum samples. Your Spike Protein Antibody results will be reported as a reference range: >/= 0.80 U/mL: This is a positive result for anti-SARS CoV-2S. EBioMedicine 77, 103902 (2022). Global Percentage of Asymptomatic SARS-CoV-2 Infections Among the Tested Population and Individuals With Confirmed COVID-19 Diagnosis: A Systematic Review and Meta-analysis. Usually your antibody levels will go up after getting a vaccine or having an infection. Stanislas Rebaudet, Such unusual characteristics, in conjunction with a highly contagious profile, resulted in the rapid spreading of the virus worldwide. e0281257. This initiative is ready to be part of the global effort to make mRNA vaccines more quickly and widely available when facing new variants or the next pandemic. Tian, J. H. et al. At week 5 (2 weeks after the second dose), all mice in both vaccinated groups showed increased NAb levels. Vaccines (Basel) 9, 874 (2021). Mice were bled at 2 weeks after each dose and antibody responses were measured by ELISA and/or neutralization assays. Slider with three articles shown per slide. COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. Guilhem Cavaille, Tissues were collected at week 5+6 days for assessment of viral RNA. CAS : reagent preparation and analysis, E.P., C.K., and K.R. Article Thus, in this study, vaccine-induced disease enhancement is less likely as demonstrated by the Th1-oriented response (Fig. 9, 1225 (2020). Recommendations based on only one study is not prudent. "Neurological phenotypes induced by SARS-CoV-2 spike protein in neurons". SARS-CoV-2 RNA levels in serum and tissue samples were quantitated using quantitative RT-PCR. 2c). In summary, this mRNA vaccine development is an effort to set up the technology platform in LMICS. Internet Explorer). N Engl J Med 383, 26032615 (2020). All isolates were quantitated by tissue culture infectious dose TCID50 using the Reed-Muench method. This was concordant with the previous findings that Omicron subvariants could evade NAb induced by the first-generation or WT-virus-based vaccines46. 8aU::fT23 Comparisons of the data between groups were made using non-parametric tests (MannWhitney test). 4d). RA-MF-28/64. 6c. 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. CAS RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge. On Day 5, significant weight reduction (p<0.05) was observed in control group when compared with the vaccinated groups. 6a). We use cookies to enhance your experience. Further information on research design is available in theNature Portfolio Reporting Summary linked to this article. The information of SARS-CoV-2 isolates including, wild-type (Wuhan-Hu1), Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants for micro-VNT50 assay performed at the Department of Microbiology, Faculty of Sciences, Mahidol University was described previously56,57. Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. Lv, J., Wu, H., Xu, J. 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). Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. All assays showed a high AUC for prediction of positive and negative results of Genscript sVNT (AUC > 0.90 for all) (Fig 2). You should not interpret the results of this test as an indication or degree of immunity or Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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