Antibody evolution to SARS-CoV-2 after single-dose Ad26.COV2.S vaccine in humans
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Abstract
The single-dose Ad.26.COV.2 (Janssen) vaccine elicits lower levels of neutralizing antibodies and shows more limited efficacy in protection against infection than either of the two available mRNA vaccines. In addition, Ad.26.COV.2 has been less effective in protection against severe disease during the Omicron surge. Here, we examined the memory B cell response to single-dose Ad.26.COV.2 vaccination. Compared with mRNA vaccines, Ad.26.COV.2 recipients had significantly lower numbers of RBD-specific memory B cells 1.5 or 6 mo after vaccination. Despite the lower numbers, the overall quality of the memory B cell responses appears to be similar, such that memory antibodies elicited by both vaccine types show comparable neutralizing potency against SARS-CoV-2 Wuhan-Hu-1, Delta, and Omicron BA.1 variants. The data help explain why boosting Ad.26.COV.2 vaccine recipients with mRNA vaccines is effective and why the Ad26.COV2.S vaccine can maintain some protective efficacy against severe disease during the Omicron surge.
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SciScore for 10.1101/2022.03.31.486548: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All participants provided written informed consent before participation in the study and the study was conducted in accordance with Good Clinical Practice.
IRB: The study was performed in compliance with all relevant ethical regulations and the protocol (DRO-1006) for studies with human participants was approved by the Institutional Review Board of the Rockefeller University.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were washed 6 times with washing buffer and then incubated with anti-human IgG, IgM or IgA secondary antibody … SciScore for 10.1101/2022.03.31.486548: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All participants provided written informed consent before participation in the study and the study was conducted in accordance with Good Clinical Practice.
IRB: The study was performed in compliance with all relevant ethical regulations and the protocol (DRO-1006) for studies with human participants was approved by the Institutional Review Board of the Rockefeller University.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were washed 6 times with washing buffer and then incubated with anti-human IgG, IgM or IgA secondary antibody conjugated to horseradish peroxidase (HRP) (Jackson ImmunoResearch 109-036-088, 109-035-129, and Sigma A0295) in blocking buffer at a 1:5,000 dilution (IgM and IgG) or 1:3,000 dilution (IgA). anti-human IgGsuggested: (Jackson ImmunoResearch Labs Cat# 109-036-088, RRID:AB_2337594)IgAsuggested: NoneThe half-maximal neutralization titers for plasma (NT50) or half-maximal and 90% inhibitory concentrations for monoclonal antibodies (IC50 and IC90) were determined using four-parameter nonlinear regression (least squares regression method without weighting; constraints: top=1, bottom=0) (GraphPad Prism). IC90suggested: NoneThe enriched B cells were incubated in Flourescence-Activated Cell-sorting (FACS) buffer (1× PBS, 2% FCS, 1 mM ethylenediaminetetraacetic acid (EDTA)) with the following anti-human antibodies (all at 1:200 dilution): anti-CD20-PECy7 (BD Biosciences, 335793), anti-CD3-APC-eFluro780 (Invitrogen, 47-0037-41), anti-CD8-APC-eFluor780 (Invitrogen, 47-0086-42), anti-CD16-APC-eFluor780 (Invitrogen, 47-0168-41), anti-CD14-APC-eFluor780 (Invitrogen, 47-0149-42), as well as Zombie NIR (BioLegend, 423105) and fluorophore-labeled Wuhan-Hu-1 RBD, NTD, and ovalbumin (Ova) for 30 min on ice. anti-CD20-PECy7suggested: Noneanti-CD3-APC-eFluro780suggested: Noneanti-CD8-APC-eFluor780suggested: Noneanti-CD16-APC-eFluor780suggested: Noneanti-CD14-APC-eFluor780suggested: NoneFor B cell phenotype analysis, in addition to above antibodies, B cells were also stained with following anti-human antibodies (all at 1:200 dilution): anti-IgD-BV650 (BD, 740594), anti-CD27-BV786 (BD biosciences, 563327), anti-CD19-BV605 (Biolegend, 302244), anti-CD71-PerCP-Cy5.5 (Biolegend, 334114), anti-IgG-PECF594 (BD, 562538), anti-IgM-AF700 (Biolegend, 314538), anti-IgA-Viogreen (Miltenyi Biotec, 130-113-481) anti-humansuggested: (Abnova Cat# H00007360-A01, RRID:AB_563327)anti-IgD-BV650suggested: Noneanti-CD27-BV786suggested: Noneanti-CD19-BV605suggested: Noneanti-CD71-PerCP-Cy5.5suggested: Noneanti-IgM-AF700 ( Biolegend , 314538) , anti-IgA-Viogreen ( Miltenyi Biotec , 130-113-481)suggested: NoneThe frequency distributions of human V genes in anti-SARS-CoV-2 antibodies from this study was compared to 131,284,220 IgH and IgL sequences generated by (50) and downloaded from cAb-Rep (51), a database of human shared BCR clonotypes available at https://cab-rep.c2b2.columbia.edu/. anti-SARS-CoV-2suggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, 293T (CRL-11268) cells were obtained from ATCC, and the cells were transfected with pNL4-3 DEnv-nanoluc and pSARS-CoV-2-SΔ19. 293Tsuggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)Recombinant DNA Sentences Resources Briefly, 293T (CRL-11268) cells were obtained from ATCC, and the cells were transfected with pNL4-3 DEnv-nanoluc and pSARS-CoV-2-SΔ19. pNL4-3suggested: NonepSARS-CoV-2-SΔ19suggested: NoneSoftware and Algorithms Sentences Resources The average of its signal was used for normalization of all the other values on the same plate with Excel software before calculating the area under the curve using Prism V9.1 (GraphPad). Excelsuggested: NonePrismsuggested: (PRISM, RRID:SCR_005375)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)For monoclonal antibodies, the ELISA half-maximal concentration (EC50) was determined using four-parameter nonlinear regression (GraphPad Prism V9.1). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)3,000 units/ml RNasin Ribonuclease Inhibitors (Promega, N2615)) per well using a FACS Aria III and FACSDiva software (Becton Dickinson) for acquisition and FlowJo for analysis. FACSDivasuggested: (BD FACSDiva Software, RRID:SCR_001456)FlowJosuggested: (FlowJo, RRID:SCR_008520)For B cell phenotype analysis, in addition to above antibodies, B cells were also stained with following anti-human antibodies (all at 1:200 dilution): anti-IgD-BV650 (BD, 740594), anti-CD27-BV786 (BD biosciences, 563327), anti-CD19-BV605 (Biolegend, 302244), anti-CD71-PerCP-Cy5.5 (Biolegend, 334114), anti-IgG-PECF594 (BD, 562538), anti-IgM-AF700 (Biolegend, 314538), anti-IgA-Viogreen (Miltenyi Biotec, 130-113-481) Biolegend , 314538) , anti-IgA-Viogreen ( Miltenyi Biotecsuggested: NoneMiltenyisuggested: (Miltenyi Biotec, RRID:SCR_008984)Sequence analysis was performed using MacVector. MacVectorsuggested: (MacVector, RRID:SCR_015700): Figures arranged in Adobe Illustrator 2022. Adobe Illustratorsuggested: (Adobe Illustrator, RRID:SCR_010279)Results from OddPub: Thank you for sharing your code and data.
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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