BNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19
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Abstract
Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) has been reported to be superior in inducing protective immunity compared to repeated application of the same vaccine. However, data comparing immunity decline after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. Here we show longitudinal monitoring of ChAd/ChAd ( n = 41) and ChAd/BNT ( n = 88) vaccinated individuals and the impact of a third vaccination with BNT. The third vaccination greatly augments waning anti-spike IgG but results in only moderate increase in spike-specific CD4 + and CD8 + T cell numbers in both groups, compared to cell frequencies already present after the second vaccination in the ChAd/BNT group. More importantly, the third vaccination efficiently restores neutralizing antibody responses against the Alpha, Beta, Gamma, and Delta variants of the virus, but neutralizing activity against the B.1.1.529 (Omicron) variant remains severely impaired. In summary, inferior SARS-CoV-2 specific immune responses following homologous ChAd/ChAd vaccination can be compensated by heterologous BNT vaccination, which might influence the choice of vaccine type for subsequent vaccination boosts.
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SciScore for 10.1101/2021.12.25.21268392: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethics committee approval: The CoCo Study and the analysis conducted for this article were approved by the Internal Review Board of Hannover Medical School (institutional review board no. 8973_BO-K_2020, 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 Binding is further revealed by an anti-tag peroxidase-labelled antibody and colorimetric quantification. anti-tag peroxidase-labelledsuggested: NonePre-incubation of the Spike-protein with serum or plasma of convalescent patients or vaccinees prevents subsequent binding to ACE2 to various … SciScore for 10.1101/2021.12.25.21268392: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethics committee approval: The CoCo Study and the analysis conducted for this article were approved by the Internal Review Board of Hannover Medical School (institutional review board no. 8973_BO-K_2020, 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 Binding is further revealed by an anti-tag peroxidase-labelled antibody and colorimetric quantification. anti-tag peroxidase-labelledsuggested: NonePre-incubation of the Spike-protein with serum or plasma of convalescent patients or vaccinees prevents subsequent binding to ACE2 to various degrees, depending on the amount of neutralizing antibodies present. ACE2suggested: NonePlates were washed three times with PBST and incubated with an HRP-conjugated anti-His-tag antibody (clone HIS 3D5, provided by Helmholtz Zentrum München) for 1⍰h at 37⍰°C. anti-His-tagsuggested: NoneNext, without washing, an antibody mix of anti-CD3-AF532 (UCHT1; #58-0038-42; Lot # 2288218; Invitrogen; 1:50), anti-CD4-BUV563 (RPA-T4; #741353; Lot # 9333607; BD Biosciences; 1:200), anti-CD8-SparkBlue 550 (SK1; #344760; Lot #B326454; Biolegend; 1:200), anti-CD45RA (HI100, #740298, Lot # 0295003; BD Biosciences; 1:200), anti-CCR7 (G043H7; #353230; Lot # B335328; Biolegend; 1:50), anti-CD38 PerCP-eF710 (HB7; #46-0388-42; Lot # 2044748; Invitrogen; 1:100) and Zombie NIR(tm) anti-CD3-AF532suggested: Noneanti-CD4-BUV563suggested: Noneanti-CD8-SparkBluesuggested: Noneanti-CD45RAsuggested: (BD Biosciences Cat# 740298, RRID:AB_2740037)anti-CCR7suggested: (Fluidigm Cat# 3159003, RRID:AB_2714155)anti-CD38suggested: (Thermo Fisher Scientific Cat# 46-0388-42, RRID:AB_1834399)Experimental Models: Cell Lines Sentences Resources Briefly, the rhabdoviral pseudotyped particles were produced in 293T cells transfected to express the desired SARS-CoV-2-S variant inoculated with VSV*DG-FLuc, a replication-deficient VSV vector that encodes for enhanced green fluorescent protein and firefly luciferase (FLuc) instead of VSV-G protein (kindly provided by Gert Zimmer, Institute of Virology and Immunology, Mittelhäusern, Switzerland) 293Tsuggested: NoneThe assay was performed in 96-well plates in which Vero cells were inoculated with the respective pseudotyped particles/plasma mixtures. Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources READER (AESKU.GROUP, Wendelsheim, Germany) and the Gen5 2.01 Software for analysis. Gen5suggested: (Gen5, RRID:SCR_017317)Statistics: Statistical analysis was done using GraphPad Prism 8.4 (GraphPad Software, USA) and SPSS 20.0.0 (IBM SPSS Statistics, USA). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)SPSSsuggested: (SPSS, RRID:SCR_002865)Ethics committee approval: The CoCo Study and the analysis conducted for this article were approved by the Internal Review Board of Hannover Medical School (institutional review board no. 8973_BO-K_2020, CoCosuggested: (CoCo, RRID:SCR_010947)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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 17 and 20. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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