Cited by 655SARS-CoV-2 and COVID-19 ResearchImmune responses and vaccinationsT-cell and B-cell Immunology

The DOI matches its Crossref record; 57 of the 59 references it cites were found in a registry or an index, and 2 are not checked yet; none of the 14 sources its claims cite is checked for support yet.

Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination

Open access

Published version of a preprint

Abstract

Key differences in both antibody and memory B cell responses to mRNA vaccination were identified on the basis of prior SARS-CoV-2 exposure.

Checked 2026-10-06 · 2 references not checked yet

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a longitudinal cohort of 44 mRNA-vaccinated adults (33 SARS-CoV-2 naïve, 11 recovered), naïve individuals required two doses for optimal antibody and memory B cell responses, including neutralization of B.1.351, whereas recovered individuals were boosted after the first dose with no further increase after the second. Pre-existing memory B cells correlated with recall antibody responses in recovered individuals, and memory B cell induction declined with age.

Key findings

  • SARS-CoV-2 naïve individuals had undetectable baseline anti-spike and anti-RBD IgG; primary vaccination increased antibodies and the booster further enhanced them. After primary immunization, ~50% developed detectable D614G neutralizing antibodies and only 4/25 developed B.1.351 neutralization above limit of detection; post-boost, all participants neutralized D614G and 26/27 neutralized B.1.351.
  • SARS-CoV-2 recovered individuals had detectable baseline anti-spike and anti-RBD IgG, which increased after the first dose but showed no additional increase after the second. Neutralizing titers against D614G and B.1.351 also peaked after the first dose with no further increase post-boost, and anti-RBD IgG levels were similar between naïve and recovered individuals at 1 week post-boost.
  • Memory B cells specific for spike and RBD were minimally detectable at baseline in naïve individuals, increased after primary vaccination, and were further boosted after the second dose, approaching levels in non-vaccinated recovered donors. Recovered individuals had baseline spike-specific memory B cells ranging from ~0.15–0.8% of total memory B cells, expanded after the first dose, and showed no additional boosting after the second.
  • Post-boost antigen-specific memory B cells showed a clear negative correlation with age, though all age groups increased over baseline. Baseline memory B cell frequency strongly correlated with post-primary antibody levels for spike and RBD in recovered individuals, while post-boost antibodies and memory B cells did not correlate in naïve individuals.

Methods

  • Longitudinal cohort of 44 healthy adults (33 SARS-CoV-2 naïve, 11 recovered; prior infection 65–275 days before vaccination) receiving Pfizer BNT162b2 or Moderna mRNA-1273, with samples at baseline, 2 weeks post-primary, day of second dose, and 1 week post-boost.
  • Assays included ELISA for anti-spike and anti-RBD IgG/IgM, VSV pseudovirus neutralization against D614G and B.1.351, flow cytometric antigen-probe detection of spike-, RBD-, and influenza HA-specific memory B cells, and BCR sequencing of sorted spike+ memory B cells from 5 recovered donors.
  • Statistical analyses used Wilcoxon tests with Holm correction, Spearman rank correlations, hierarchical clustering, principal component analysis, and multivariable linear regression controlling for sex and age.

Limitations

  • Stated: the study was small and designed for deep immunological analysis, so it could not directly address protection or true vaccine efficacy; larger clinical studies are needed to examine one versus two doses in recovered individuals. The cohort consisted of individuals not hospitalized during SARS-CoV-2 infection, and identifying recovered individuals by self-report or laboratory tests may be practically challenging.
  • Stated: the timeframe was short, durability and long-term immunological memory remain unknown, and SHM analyses were limited to a small number of individuals and the first few weeks after vaccination. The cohort was not extensively enriched in those over 50 years old and does not directly address elderly vaccinees.
  • Evident: the small sample size limits subgroup analyses, the healthy/no chronic-condition cohort limits generalizability, and some comparisons used unpaired tests because of missing data or samples for some participants.

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Integrity signals

Registry

Crossref · 10.1126/sciimmunol.abi6950

Cites

57 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 14 cited sources checked · 0 supported · 0 flagged

Show all 61 claims

  • It may state two separate claims as one. 13
  • The quote only partly states this claim. 1
  • Probably not a substantial claim. 18
27 of 27
  • The paper relies on this without support.

    The prior SARS-CoV-2 infection status of recovered individuals is accurately known.

    “Of this cohort, 11 individuals had a prior SARS-CoV-2 infection, ranging from 65 to 275 days prior to vaccination.”
    “Moreover, there may be practical challenges to identifying SARS-CoV-2 recovered individuals based on self-reported infection or laboratory confirmed tests such as RT-PCR or serology.”
  • The authors state this as an assumption.

    Pre-existing spike-binding memory B cell clones present before vaccination in recovered individuals arose during the initial SARS-CoV-2 infection.

    “These clones, which were present before the first vaccine dose, presumably arose during the initial infection with SARS-CoV-2.”
  • The paper relies on this without support.

    The mRNA vaccines BNT162b2 and mRNA-1273 are similar enough to be analyzed together as mRNA vaccines.

    “who received SARS-CoV-2 mRNA vaccines (Pfizer BNT162b2 or Moderna mRNA-1273) at the University of Pennsylvania Health System”
    “Here, we demonstrated that mRNA vaccines to SARS-CoV-2 induced robust antibody and memory B cell responses to full-length spike and the RBD.”
  • The paper relies on this without support.

    The measured antibody and memory B cell responses are relevant to vaccine efficacy or protection.

    “These results are encouraging for both short- and long-term vaccine efficacy and add to our understanding of SARS-CoV-2 mRNA vaccine-induced immune responses in several ways.”
    “The data presented document key differences in immune responses associated with vaccine efficacy in SARS-CoV-2 naïve versus SARS-CoV-2 recovered individuals.”
  • The paper relies on this without support.

    Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.

    “All subjects received either Pfizer (BNT162b2) or Moderna (mRNA-1273) mRNA vaccines.”
  • The paper relies on this without support.

    Self-reported health screening accurately identifies participants without chronic health conditions.

    “All participants were otherwise healthy and based on self-reported health screening did not report any history of chronic health conditions.”
  • The paper relies on this without support.

    Memory B cells are important for durability of immune memory and potential recall responses to infection or future booster vaccination.

    “which are important for durability of immune memory and potential recall responses to infection or future booster .”
  • The paper relies on this without support.

    High circulating titers of neutralizing antibodies are common surrogates of protective immunity.

    “Although high circulating titers of neutralizing antibodies are common surrogates of protective immunity”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting counts for B.1.351 neutralization after the first dose

    Major

    The Results state that 4 of 25 SARS-CoV-2 naïve individuals developed detectable B.1.351 neutralization after the first dose, whereas the Discussion states that only 2 of 25 did.

1 of 1

Citations

Cites

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Research works printed but not linked: 1

  1. R. Levi, E. Azzolini, C. Pozzi, L. Ubaldi, M. Lagioia, A. Mantovani, M. Rescigno, A cautionary note on recall vaccination in ex-COVID-19 subjects. medRxiv 10.1101/2021.02.01.21250923 (2021). · DOI

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Metadata

Authors
Goel, R. R., Apostolidis, S. A., Painter, M. M., Mathew, D., Pattekar, A., Kuthuru, O., Gouma, S., Hicks, P., Meng, W., Rosenfeld, A. M., Dysinger, S., Lundgreen, K. A., Kuri-Cervantes, L., Adamski, S., Hicks, A., Korte, S., Oldridge, D. A., Baxter, A. E., Giles, J. R., Weirick, M. E., McAllister, C. M., Dougherty, J., Long, S., D’Andrea, K., Hamilton, J. T., Betts, M. R., Luning Prak, E. T., Bates, P., Hensley, S. E., Greenplate, A. R., & Wherry, E. J.
Affiliations
  • University of Pennsylvania (US)
  • Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Corresponding author
  • Goel, Rishi R.
  • Apostolidis, Sokratis A.
  • Painter, Mark M.
  • Mathew, Divij
  • Wherry, E. John
Venue
Science Immunology
Published
2021-04-02
Volume
6
Issue
58
ISSN
2470-9468 (ISSN-L)
OpenAlex
W3155262144
Cited by
655
References
54
Citations by year
2026: 31 · 2025: 55 · 2024: 73 · 2023: 112 · 2022: 230 · 2021: 153
FWCI
44.92
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Immunology (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (AI105343, AI082630, AI108545, AI155577, AI149680, AI152236, HL143613, T32 AI055400, P30-AI0450080, T32 CA009140, T32 AR076951-01, U19AI082630)
  • University of Pennsvlvania (21st Century Scholar Fund, COVID Research Fund)
  • Cancer Research Institute (Mark Foundation Fellowship)
  • Chen Family Research Fund
  • Parker Institute for Cancer Immunotherapy
  • Paul G. Allen Frontiers Group
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
SARS-CoV-2, COVID-19 pandemic, mRNA vaccines, memory B cells, antibody response, neutralizing antibodies, prior SARS-CoV-2 infection, recovered patients, B.1.351 variant, spike protein receptor-binding domain, booster vaccination, age-related immune decline, cell-mediated immunity

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