A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates
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Abstract
Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>10 4 ) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log 10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.
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SciScore for 10.1101/2021.07.13.452251: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Immunization of non-human primates: 18 cynomolgus macaques were randomly allocated to groups. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were coated with mouse anti-human IFN-γ antibody (BD Pharmigen) at 5 μg/well and incubated at 4°C overnight. anti-human IFN-γsuggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, HEK293T cells were co-transfected with: 1) the packaging plasmid psPAX2 (AIDS Resource and Reagent Program), 2) luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene), and 3) an S protein-expressing … SciScore for 10.1101/2021.07.13.452251: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Immunization of non-human primates: 18 cynomolgus macaques were randomly allocated to groups. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were coated with mouse anti-human IFN-γ antibody (BD Pharmigen) at 5 μg/well and incubated at 4°C overnight. anti-human IFN-γsuggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, HEK293T cells were co-transfected with: 1) the packaging plasmid psPAX2 (AIDS Resource and Reagent Program), 2) luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene), and 3) an S protein-expressing plasmid, pcDNA3.1-SARS CoV-2 SΔCT using lipofectamine 2000 (ThermoFisher). HEK293Tsuggested: NoneTo determine the neutralization activity of the serum samples from nonhuman primates, HEK293T-hACE2 cells were seeded in 96-well tissue culture plates at a density of 1.75 x 104 cells/well and incubated overnight. HEK293T-hACE2suggested: RRID:CVCL_A7UK)Recombinant DNA Sentences Resources Briefly, HEK293T cells were co-transfected with: 1) the packaging plasmid psPAX2 (AIDS Resource and Reagent Program), 2) luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene), and 3) an S protein-expressing plasmid, pcDNA3.1-SARS CoV-2 SΔCT using lipofectamine 2000 (ThermoFisher). psPAX2suggested: RRID:Addgene_12260)pLenti-CMVsuggested: NonepcDNA3.1-SARS CoV-2 SΔCTsuggested: NoneTo generate a standard, a fragment of the subgenomic E gene was synthesized and cloned into a pcDNA3.1+ expression plasmid using restriction site cloning (Integrated DNA Techonologies). pcDNA3.1+suggested: RRID:Addgene_117272)Software and Algorithms Sentences Resources For each sample, endpoint titer was calculated in Graphpad Prism software, using a four-parameter logistic curve fit to calculate the reciprocal serum dilution that yields an absorbance value of 0.2 at 450nm. Graphpad Prismsuggested: (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: No clinical trial numbers were referenced.
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.
Results from scite Reference Check: We found no unreliable references.
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