The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity
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Abstract
mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, β, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, β, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of β and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.
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SciScore for 10.1101/2021.05.07.21256821: (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 not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources After washing, plates were incubated with horseradish peroxidase (HRP)-conjugated anti-human Ig secondary antibodies diluted in PBS containing 0.05% Tween 20 1% BSA for 45 min at RT. anti-human Ig secondarysuggested: NoneTo analyze RBD-specific IgG antibody subclasses, HRP-conjugated anti-human IgG1, IgG2, IgG3 and IgG4 (Southern Biotech) were used at a 1:3000 dilutions. anti-human IgG1suggested: NoneIgG4suggested: NoneTo quantitate the level of each viral antigen-specific antibody class or subclasses optical density … SciScore for 10.1101/2021.05.07.21256821: (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 not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources After washing, plates were incubated with horseradish peroxidase (HRP)-conjugated anti-human Ig secondary antibodies diluted in PBS containing 0.05% Tween 20 1% BSA for 45 min at RT. anti-human Ig secondarysuggested: NoneTo analyze RBD-specific IgG antibody subclasses, HRP-conjugated anti-human IgG1, IgG2, IgG3 and IgG4 (Southern Biotech) were used at a 1:3000 dilutions. anti-human IgG1suggested: NoneIgG4suggested: NoneTo quantitate the level of each viral antigen-specific antibody class or subclasses optical density (OD) values were measured and the area under the curve (AUC) derived from optical density measurements of four serial dilutions was determined using Prism 8 (GraphPad). antigen-specificsuggested: NoneSoftware and Algorithms Sentences Resources To quantitate the level of each viral antigen-specific antibody class or subclasses optical density (OD) values were measured and the area under the curve (AUC) derived from optical density measurements of four serial dilutions was determined using Prism 8 (GraphPad). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Data analysis and visualization: GraphPad Prism (version 8.0) was used to conduct statistical analyses. GraphPad Prismsuggested: (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 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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