The SARS-CoV-2 mRNA-1273 vaccine elicits more RBD-focused neutralization, but with broader antibody binding within the RBD
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Abstract
The emergence of SARS-CoV-2 variants with mutations in key antibody epitopes has raised concerns that antigenic evolution will erode immunity. The susceptibility of immunity to viral evolution is shaped in part by the breadth of epitopes targeted. Here we compare the specificity of antibodies elicited by the mRNA-1273 vaccine versus natural infection. The neutralizing activity of vaccine-elicited antibodies is even more focused on the spike receptor-binding domain (RBD) than for infection-elicited antibodies. However, within the RBD, binding of vaccine-elicited antibodies is more broadly distributed across epitopes than for infection-elicited antibodies. This greater binding breadth means single RBD mutations have less impact on neutralization by vaccine sera than convalescent sera. Therefore, antibody immunity acquired by different means may have differing susceptibility to erosion by viral evolution.
One Sentence Summary
Deep mutational scanning shows the mRNA-1273 RBD-binding antibody response is less affected by single viral mutations than the infection response.
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SciScore for 10.1101/2021.04.14.439844: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Due to the de-identified nature of the samples, the work described in this paper was deemed non-human subjects research by the Fred Hutchinson Cancer Research Center Institutional Review Board. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources All data from this cohort (i.e., the neutralization and RBD- and spike-binding activity of plasmas pre- and post-depletion of RBD-binding antibodies in Fig. 1 and RBD-binding escape maps in Fig. 4, S6B, and S7) were previously reported (15) with the exception of … SciScore for 10.1101/2021.04.14.439844: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Due to the de-identified nature of the samples, the work described in this paper was deemed non-human subjects research by the Fred Hutchinson Cancer Research Center Institutional Review Board. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources All data from this cohort (i.e., the neutralization and RBD- and spike-binding activity of plasmas pre- and post-depletion of RBD-binding antibodies in Fig. 1 and RBD-binding escape maps in Fig. 4, S6B, and S7) were previously reported (15) with the exception of neutralization assays in Fig. 5, S8, and S9, which were newly performed in this study. S6Bsuggested: NoneS9suggested: NoneAfter the serum incubations, the libraries were secondarily labeled with 1:100 FITC-conjugated anti-MYC antibody (Immunology Consultants Lab, CYMC-45F) to label for RBD expression and 1:200 Alexa-647-conjugated goat anti-human-IgA+IgG+IgM (Jackson ImmunoResearch 109-605-064) to label for bound serum antibodies. anti-MYCsuggested: Noneanti-human-IgA+IgG+IgMsuggested: NoneMagnetic Separation Rack, ThermoFisher CS15000) was used to separate antibodies that bind RBD from the supernatant, and the supernatant (the post-RBD antibody depletion sample) was removed. post-RBDsuggested: NoneDilution series of the “synthetic” sera comprised of the anti-RBD antibody rREGN10987 (49) or anti-NTD antibody r4A8 (21) and pooled pre-pandemic human serum from 2017-2018 (Gemini Biosciences; nos. 100–110, lot H86W03J; pooled from 75 donors) were performed such that the anti-spike antibody was present at a highest concentration of 0.25 μg/mL. anti-RBDsuggested: Noneanti-NTDsuggested: Noneanti-spikesuggested: NoneAntibody binding was detected with TMB/E HRP substrate (Millipore Sigma, ES001) and 1 N HCl was used to stop the reaction. ES001suggested: NoneExperimental Models: Cell Lines Sentences Resources Cell lines: HEK-293T (ATCC CRL-3216) cells were used to generate SARS-CoV-2 spike-pseudotyped lentiviral particles and 293T-ACE2 cells (BEI NR-52511) were used to titer the SARS-CoV-2 spike-pseudotyped lentiviral particles and to perform neutralization assays (see HEK-293Tsuggested: ATCC Cat# CRL-3216, RRID:CVCL_0063)293T-ACE2suggested: RRID:CVCL_YZ65)Software and Algorithms Sentences Resources Magnetic beads conjugated to the SARS-CoV-2 RBD (AcroBiosystems, MBS-K002) were prepared according to the manufacturer’s protocol. AcroBiosystemssuggested: (ACRObiosystems, RRID:SCR_012550)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:A caveat is that some differences could also be because the vaccinated individuals were relatively young (18–55 years) and healthy, whereas the convalescent individuals were older (23–76 years, median 56) with a range of comorbidities (13). More generally, our findings suggest that it is important to differentiate antibody immunity acquired by different means when assessing the impact of viral evolution. Significant effort is being expended to identify emerging antigenic variants of SARS-CoV-2 and determine which ones might evade immunity (3, 7, 8, 33). Our findings suggest that the results could vary depending on the source of immunity. Furthermore, carefully characterizing and comparing the specificity of antibody immunity elicited by additional vaccine modalities could provide a basis for determining whether some will be more resistant to viral evolution.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04283461 Active, not recruiting Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1… 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.
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