Limiting the priming dose of a SARS CoV-2 vaccine improves virus-specific immunity
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Abstract
Since late 2019, SARS-CoV-2 has caused a global pandemic that has infected 128 million people worldwide. Although several vaccine candidates have received emergency use authorization (EUA), there are still a limited number of vaccine doses available. To increase the number of vaccinated individuals, there are ongoing discussions about administering partial vaccine doses, but there is still a paucity of data on how vaccine fractionation affects vaccine-elicited immunity. We performed studies in mice to understand how the priming dose of a SARS CoV-2 vaccine affects long-term immunity to SARS CoV-2. We first primed C57BL/6 mice with an adenovirus-based vaccine encoding SARS CoV-2 spike protein (Ad5-SARS-2 spike), similar to that used in the CanSino and Sputnik V vaccines. This prime was administered either at a low dose (LD) of 10 6 PFU or at a standard dose (SD) of 10 9 PFU, followed by a SD boost in all mice four weeks later. As expected, the LD prime induced lower immune responses relative to the SD prime. However, the LD prime elicited immune responses that were qualitatively superior, and upon boosting, mice that were initially primed with a LD exhibited significantly more potent immune responses. Overall, these data demonstrate that limiting the priming dose of a SARS CoV-2 vaccine may confer unexpected benefits. These findings may be useful for improving vaccine availability and for rational vaccine design.
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SciScore for 10.1101/2021.03.31.437931: (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 performed with approval of the Northwestern University Institutional Animal Care and Use Committee (IACUC). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mice were purchased from Jackson laboratories (approximately half males and half females). Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Cells were stained with fluorescently-labeled antibodies against CD8α (53-6.7 on PerCP-Cy5.5), CD44 (IM7 on Pacific Blue), TNFα (MP6-XT22 on PE-Cy7), IL-2 (JES6-5H4 on PE), IFNγ (XMG1.2 on APC), peanut agglutinin or PNA (conjugated to fluorescein), Fas … SciScore for 10.1101/2021.03.31.437931: (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 performed with approval of the Northwestern University Institutional Animal Care and Use Committee (IACUC). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mice were purchased from Jackson laboratories (approximately half males and half females). Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Cells were stained with fluorescently-labeled antibodies against CD8α (53-6.7 on PerCP-Cy5.5), CD44 (IM7 on Pacific Blue), TNFα (MP6-XT22 on PE-Cy7), IL-2 (JES6-5H4 on PE), IFNγ (XMG1.2 on APC), peanut agglutinin or PNA (conjugated to fluorescein), Fas (Jo2 on PE), IgD (11-26 on Pacific Blue), IgM (RMM-1 on PECy7), B220 (RA3-6B2 on PerCP-Cy5.5), and CD3 (145-2c11 on FITC). CD8αsuggested: NoneCD44suggested: NonePNAsuggested: NoneB220suggested: NoneCD3suggested: (Fitzgerald Industries International Cat# 61R-1452, RRID:AB_11199165)Experimental Models: Cell Lines Sentences Resources These vaccines were propagated on trans-complementing HEK293 cells (ATCC), purified by cesium chloride density gradient centrifugation, titrated, and then frozen at −80 °C. HEK293suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)Experimental Models: Organisms/Strains Sentences Resources Single cell RNA-Seq Data Acquisition and Analysis: C57BL/6 mice were immunized with a LD (106 PFU) or a SD (109 PFU) of Ad5-SARS-2 spike, and at day 28, splenic CD8 T cells were MACS-sorted with a MACS negative selection kit (STEMCELL). C57BL/6suggested: NoneSoftware and Algorithms Sentences Resources Flow cytometry samples were acquired with a Becton Dickinson Canto II or an LSRII and analyzed using FlowJo (Treestar). FlowJosuggested: (FlowJo, RRID:SCR_008520)Further analyses were performed in R using the Seurat package v4.0 (PMID: 30638736), as previously described (21). Seuratsuggested: (SEURAT, RRID:SCR_007322)Terminal effector gene signatures were derived using the edgeR package (22), comparing effector memory to terminal effector CD8 T cells (3). edgeRsuggested: (edgeR, RRID:SCR_012802)Data were analyzed using Prism (Graphpad). Prismsuggested: (PRISM, RRID:SCR_005375)Graphpadsuggested: (GraphPad, RRID:SCR_000306)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.
- No funding statement was detected.
- No protocol registration statement was detected.
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