S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
Article activity feed
-
SciScore for 10.1101/2020.09.24.311027: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All mouse experiments were approved by the institutional animal care and use committee (IACUC) and were conducted according to international guidelines for animal studies.
IRB: Human COVID-19 convalescent serum samples: 41 human convalescent sera samples from recovered COVID-19 patients (table S1) were obtained from Public Health Clinical Center of Chengdu in Chengdu, China, under approved guidelines by the Institutional Review Board (IRB), and all patients had provided written informed consent before sera sample were collected.
Consent: Human COVID-19 convalescent serum samples: 41 human convalescent sera samples from recovered COVID-19 patients (table S1) …SciScore for 10.1101/2020.09.24.311027: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All mouse experiments were approved by the institutional animal care and use committee (IACUC) and were conducted according to international guidelines for animal studies.
IRB: Human COVID-19 convalescent serum samples: 41 human convalescent sera samples from recovered COVID-19 patients (table S1) were obtained from Public Health Clinical Center of Chengdu in Chengdu, China, under approved guidelines by the Institutional Review Board (IRB), and all patients had provided written informed consent before sera sample were collected.
Consent: Human COVID-19 convalescent serum samples: 41 human convalescent sera samples from recovered COVID-19 patients (table S1) were obtained from Public Health Clinical Center of Chengdu in Chengdu, China, under approved guidelines by the Institutional Review Board (IRB), and all patients had provided written informed consent before sera sample were collected.Randomization Rhesus Macaques (3-6 years old) were randomized into 3 groups of 6 animals, and immunized intramuscularly with either PBS as a negative control, or 30 μg S-Trimer adjuvanted with 0.25 mL AS03, or 30 μg S-Trimer adjuvanted with 1.5 mg CpG 1018 plus 0.75 mg alum. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animal studies, facilities and ethics statements: Specific pathogen-free (SPF) BALB/c female mice (6-8 weeks old) for immunogenicity studies were purchased from Chengdu Dossy Experimental Animals Co., Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After washing 3 times with PBST, the plates were incubated with rabbit anti-Trimer-Tag antibody (Clover Biopharma) at 37°C for 1 h, followed by washing 3 times with PBST and then a 1:20000 dilution of goat anti-rabbit IgG-HRP (Southern Biotech). anti-Trimer-Tagsuggested: Noneanti-rabbit IgG-HRPsuggested: NoneAfter washing 3 times with PBST, the plates were incubated with rabbit anti-Trimer-Tag antibody (Clover Biopharma) at 37°C for 1 h, followed by washing 3 times with PBST and then a 1:20000 dilution of goat anti-rabbit IgG-HRP (Southern Biotech). anti-Trimer-Tagsuggested: Noneanti-rabbit IgG-HRPsuggested: NoneExperimental Models: Cell Lines Sentences Resources Then, freshly-trypsinized Vero-E6 cells were added to each well at 20000 cells/well. Vero-E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animal studies, facilities and ethics statements: Specific pathogen-free (SPF) BALB/c female mice (6-8 weeks old) for immunogenicity studies were purchased from Chengdu Dossy Experimental Animals Co., BALB/csuggested: NoneSprague Dawley (SD) rats immunogenicity studies were performed at JOINN Laboratories Inc. (Suzhou, China), and SD rats (6-9 weeks old) were purchased from Zhejiang Vital River Laboratory Animal Technology Co., Ltd. Studies with SD rats were compliant with the policies of JOINN Laboratories Inc., the Guide for the Care and Use of Laboratory Animals (8th Edition, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council; National Academy Press; Washington, D.C., 2010), and the U.S. Department of Agriculture through the Animal Welfare Act (Public Law 99-198). Sprague Dawleysuggested: NoneThe expression vector was then stably transfected into GH-CHO (dhfr -/-) cell line and high expression clones were selected and adapted to SFM-4-CHO (Hyclone) serum free medium and ACE2-Fc was produced in 15 L bioreactors, as described for Endo180-Fc above. dhfr -/-suggested: NoneSoftware and Algorithms Sentences Resources After stepwise gene amplification with increasing concentrations (0.0–10 nM) of MTX (Sigma), the clones producing the highest S-Trimer titer were then adapted to SFM-4CHO serum-free medium (GE BioSciences). GE BioSciencessuggested: NoneStatistical analysis: Statistical analyses were performed using the Prism 8.0 (GraphPad Software). Prismsuggested: (PRISM, RRID:SCR_005375)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04405908 Active, not recruiting SCB-2019 as COVID-19 Vaccine Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
-
-
SciScore for 10.1101/2020.09.24.311027: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Convalescent Sera (n=40) 0.75 Pseudovirus Neutralization Titer - EC50 ACE2-Competitive Titer (EC50) ACE2-Competitive Titer Male (n = 17) 1.5 Gender Female 2.5 (n = 17) GMT: GMT: 0.5 Male (n = 16) Female 1.5 Gender 2.5 Pseudovirus Neutralization Titer - EC50 (Log) GMT: Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody Titer - EC50 (Log) GMT: 0.5 C 1,682 PsV Neutralization Titer (EC50) Pseudovirus Neutralization Titer ACE2-Competitive Titer - EC50 (Log) GMT: 1,039 0.85 0.95 1.05 1.15 1.25 Human COVID-19 … SciScore for 10.1101/2020.09.24.311027: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Convalescent Sera (n=40) 0.75 Pseudovirus Neutralization Titer - EC50 ACE2-Competitive Titer (EC50) ACE2-Competitive Titer Male (n = 17) 1.5 Gender Female 2.5 (n = 17) GMT: GMT: 0.5 Male (n = 16) Female 1.5 Gender 2.5 Pseudovirus Neutralization Titer - EC50 (Log) GMT: Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody Titer - EC50 (Log) GMT: 0.5 C 1,682 PsV Neutralization Titer (EC50) Pseudovirus Neutralization Titer ACE2-Competitive Titer - EC50 (Log) GMT: 1,039 0.85 0.95 1.05 1.15 1.25 Human COVID-19 EC50suggested: NoneExperimental Models: Cell Lines Sentences Resources J Biol Chem 275, 1993-2002 (2000). doi: 10.1074/jbc.275.3.1993 N.M. Inocencio, J.F. Sucic, J.M. Moehring, M.J. Spence, T.J. Moehring, Endoprotease activities other than furin and PACE4 with a role in processing of HIV-I gp160 glycoproteins in CHO-K1 cells. CHO-K1suggested: CLS Cat# 603480/p693_CHO-K1, RRID:CVCL_0214)C) Reducing SDS-PAGE analysis with Coomassie Blue staining of high-level expression of S-Trimer as a secreted protein from CHO cells in a 15L bioreactor Fed-batch serum-free culture over 11 days (10 µL of cleared media were loaded for each sample) along with a purified standard (Std). CHOsuggested: NoneExperimental Models: Organisms/Strains Sentences Resources BALB/c mice (n=7-8/group) were immunized with various doses of S-Trimer that was non-adjuvanted or adjuvanted with 25 µL AS03, 10 µg CpG 1018, or µg CpG 1018 plus 50 µg alum twice on Day 0 and Day 21. BALB/csuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04405908 Recruiting SCB-2019 as COVID-19 Vaccine Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
-
