Loss of Neutralizing Antibody Response to mRNA Vaccination against SARS-CoV-2 Variants: Differing Kinetics and Strong Boosting by Breakthrough Infection
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Abstract
The waning efficacy of SARS-CoV-2 vaccines combined with the continued emergence of variants resistant to vaccine-induced immunity has reignited debate over the need for booster vaccines. To address this, we examined the neutralizing antibody (nAb) response against four major SARS-CoV-2 variants—D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2)—in health care workers (HCWs) at pre-vaccination, post-first and post-second mRNA vaccine dose, and six months post-second mRNA vaccine dose. Neutralizing antibody titers against all variants, especially the Delta variant, declined dramatically from four weeks to six months post-second mRNA vaccine dose. Notably, SARS-CoV-2 infection enhanced vaccine durability, and mRNA-1273 vaccinated HCWs also exhibited ~2-fold higher nAb titers than BNT162b2 vaccinated HCWs. Together these results demonstrate possible waning of protection from infection against SARS-CoV-2 Delta variant based on decreased nAb titers, dependent on COVID-19 status and the mRNA vaccine received.
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SciScore for 10.1101/2021.12.06.471455: (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 These 48 HCWs ranged in age from 22-61 years (median = 37; IQR = 31.75-43.25) and included 26 male and 22 female HCWs. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were then washed and treated with 100 μL of HRP labeled anti-human-IgG antibody (31220, EDI, San Diego, CA) for 30 min. anti-human-IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cell Lines and Maintenance: HEK293T cells (CRL-11268, CVCL_1926, ATCC, Manassas, VA) and HEK293T-ACE2 cells (NR-52511, BEI Resources, ATCC, Manassas, VA) were maintained in … SciScore for 10.1101/2021.12.06.471455: (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 These 48 HCWs ranged in age from 22-61 years (median = 37; IQR = 31.75-43.25) and included 26 male and 22 female HCWs. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Plates were then washed and treated with 100 μL of HRP labeled anti-human-IgG antibody (31220, EDI, San Diego, CA) for 30 min. anti-human-IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cell Lines and Maintenance: HEK293T cells (CRL-11268, CVCL_1926, ATCC, Manassas, VA) and HEK293T-ACE2 cells (NR-52511, BEI Resources, ATCC, Manassas, VA) were maintained in Dulbeco’s Modified Eagles Medium (Gibco, 11965-092, ThermoFisher Scientific, Waltham, MA) supplemented with 10% (v/v) HEK293Tsuggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)CVCL_1926suggested: NoneTo determine relative titers of harvested virus, the pseudotyped virus for each of the SARS-CoV-2 variants were used to infect HEK293T-ACE2 cells. HEK293T-ACE2suggested: NoneRecombinant DNA Sentences Resources Constructs for Pseudotyping Virus Production: Production of lentiviral pseudotyped virus was performed using a previously reported protocol using pNL4-3-HIV-1-inGluc vector (13, 14, 21–23). pNL4-3-HIV-1-inGlucsuggested: NoneThis vector is a pNL4-3-HIV-1 ΔEnv construct and contains a Gaussia luciferase reporter gene with a CMV promoter both oriented in an anti-sense orientation relative to the HIV-1 genome. pNL4-3-HIV-1 ΔEnvsuggested: NoneConstructs encoding N- and C-terminal flag-tagged SARS-CoV-2 spike (S) for each variant — D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) — were synthesized and cloned into pcDNA3.1 vector using KpnI/BamHI restriction enzyme cloning by GenScript BioTech (Piscataway, NJ). pcDNA3.1suggested: RRID:Addgene_79663)Software and Algorithms Sentences Resources Neutralizing titer 50% (NT50) for each serum sample was determined by non-linear regression with least squares fit in GraphPad Prism 5 (GraphPad Software, San Diego, California) GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)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: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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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