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Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination
Open accessPublished 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.
Overview
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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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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose.”
- Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
“these antibody responses were significantly increased after the first dose of vaccine (Fig. 1B).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At baseline, SARS-CoV-2 naïve individuals had undetectable levels of IgG antibodies specific for either full-length spike protein or the spike receptor binding domain (RBD) (Fig. 1B).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Antibody responses to SARS-CoV-2 mRNA vaccination
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant.”
- Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
“primary immunization was largely ineffective to induce functional antibodies against the B.1.351 variant with only 4/25 individuals developing neutralizing titers above limit of detection over the same time frame (Fig. 1C-D).”
- Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
“Neutralizing titers were significantly increased after the second dose in SARS-CoV-2 naïve individuals, with all participants achieving neutralization against D614G and 26/27 achieving detectable neutralization against B.1.351 at 7 days post-boost (Fig. 1C-D).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens.”
- Also stated in: § Relationships between antibody and memory B cell responses to SARS-CoV-2 mRNA vaccination · boosted
“the baseline frequency of antigen-specific memory B cells strongly correlated with post-primary vaccination antibody levels for both spike and RBD (Fig. 4D), consistent with the notion that these pre-vaccination memory B cells are major contributors to the SARS-CoV-2 antibody recall response.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Relationships between antibody and memory B cell responses to SARS-CoV-2 mRNA vaccination · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“though the memory B cell response declined slightly with age.”
- Also stated in: § Demographic and clinical factors associate with B cell responses to SARS-CoV-2 mRNA vaccination · boosted
“there was a clear negative correlation between the post-boost frequency of antigen-specific memory B cells and age (Fig. 3D).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Demographic and clinical factors associate with B cell responses to SARS-CoV-2 mRNA vaccination · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age.”
- Also stated in: § Memory B Cell responses to SARS-CoV-2 mRNA vaccination · plain
“These memory B cells were also significantly boosted after adminstration of the second vaccine dose, approaching the levels of memory B cells observed in non-vaccinated SARS-CoV-2 recovered donors (Fig. 2B).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Memory B Cell responses to SARS-CoV-2 mRNA vaccination · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, in SARS-CoV-2 recovered subjects, there was no additional increase in antibody levels following the second vaccine dose (Fig. 1B).”
- Also stated in: § Abstract · plain
“however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Antibody responses to SARS-CoV-2 mRNA vaccination
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SHM levels in the overlapping clones did not increase after vaccination (Fig. 2F).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Memory B Cell responses to SARS-CoV-2 mRNA vaccination
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In the paper
“Indeed, pre-existing memory B cells in SARS-CoV-2 recovered subjects correlated strongly with post-vaccination antibody levels in our cohort”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such a trend was not observed for the memory B cell response (Fig. 3E).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Demographic and clinical factors associate with B cell responses to SARS-CoV-2 mRNA vaccination
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- It may state two separate claims as one. 13
- The quote only partly states this claim. 1
- Probably not a substantial claim. 18
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure”
- Also stated in: § DISCUSSION · boosted
“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.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The mRNA vaccines BNT162b2 and mRNA-1273 are similar enough to be analyzed together as mRNA vaccines.
- Also stated in: § DISCUSSION · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Primary vaccination induced a significant increase in SARS-CoV-2-specific antibodies, that was further enhanced by the booster dose (Fig. 1B).”
- Also stated in: § Abstract · plain
“SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Antibody responses to SARS-CoV-2 mRNA vaccination
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose.”
- Also stated in: § Memory B Cell responses to SARS-CoV-2 mRNA vaccination · plain
“SARS-CoV-2 recovered individuals had a robust expansion of spike- and RBD-specific memory B cells following primary immunization, but had no additional boosting after the second vaccine dose (Fig. 2B).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Memory B Cell responses to SARS-CoV-2 mRNA vaccination · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SARS-CoV-2 experienced individuals had a robust increase in neutralizing antibodies following primary immunization, with no further increase in neutralization titers against D614G and B.1.351 after the second dose (Fig. 1C).”
- Also stated in: § DISCUSSION · plain
“neutralizing titers against both D614G and the B.1.351 South African variant reached a peak after the first dose in recovered subjects.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Antibody responses to SARS-CoV-2 mRNA vaccination
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § DISCUSSION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the frequency of IgG+ memory B cells increased slightly to ~75% following the first dose of vaccine, further increases were not observed after the second immunization (Fig. 2C-D).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Memory B Cell responses to SARS-CoV-2 mRNA vaccination
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“In examining correlates of vaccine-induced immune responses, we also uncovered a trend suggesting that vaccine-induced side effects may be related to post-vaccination serum antibodies, but not memory B cells.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“The frequency of these antigen-unrelated memory B cells remained stable throughout the mRNA vaccination timecourse (Fig. 2B), confirming the specificity of this memory B cell assay.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Memory B Cell responses to SARS-CoV-2 mRNA vaccination
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In the paper
“On day 15 after primary immunization, ~25-30% of spike-specific memory B cells were IgG+ and ~40-50% were IgM+ in SARS-CoV-2 naïve individuals (Fig. 2C).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Memory B Cell responses to SARS-CoV-2 mRNA vaccination
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In the paper
“Of the self-reported naïve subjects, one individual was found to have positive SARS-CoV-2 specific antibodies and memory B cells at baseline and was retroactively classified as SARS-CoV-2 recovered.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Recruitment and Clinical Sample Collection
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In the paper
“All timepoints for individual subjects were run in the same experiment to minimize batch effects.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Flow Cytometry and Cell Sorting
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None of the sources cited for this claim have been checked yet.
In the paper
“Timepoints were chosen a priori to capture the peak antigen-specific response for primary (41) and secondary responses (42, 43) in SARS-CoV-2 naïve individuals.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Recruitment and Clinical Sample Collection
What the sources say
- Not checked yetcites [41] J. D. Miller, R. G. van der Most, R. S. Akondy, J. T. Glidewell, S. Albott, D. Masopust, K. Murali-Krishna, P. L. Mahar, S. Edupuganti, S. Lalor, S. Germon, C. Del Rio, M. J. J. Mulligan, S. I. Staprans, J. D. Altman, M. B. Feinberg, R. Ahmed, Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity 28, 710– 722 (2008). 10.1016/j.immuni.2008.02.020 18468462 source
- Not checked yetcites [42] D. V. Dolfi, K. D. Mansfield, R. K. Kurupati, S. Kannan, S. A. Doyle, H. C. J. Ertl, K. E. Schmader, E. J. Wherry, Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans. PLOS ONE 8, e77164 (2013). 10.1371/journal.pone.0077164 24155927 PMC3796569 source
- Not checked yetcites [43] R. S. Herati, M. A. Reuter, D. V. Dolfi, K. D. Mansfield, H. Aung, O. Z. Badwan, R. K. Kurupati, S. Kannan, H. Ertl, K. E. Schmader, M. R. Betts, D. H. Canaday, E. J. Wherry, Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. J. Immunol. 193, 3528– 3537 (2014). 10.4049/jimmunol.1302503 25172499 PMC4170011 source
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In the paper
“Two biological replicates were run on all samples.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > B Cell Receptor (BCR) Sequencing
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In the paper
“Conversely, a single dose of vaccine was able to achieve highly effective antibody responses in SARS-CoV-2 recovered individuals with no further improvement post-boost.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > RESULTS > Antibody responses to SARS-CoV-2 mRNA vaccination
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In the paper
“All participants were otherwise healthy and based on self-reported health screening did not report any history of chronic health conditions.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Recruitment and Clinical Sample Collection
Strength:plain· not yet calibratedn = 44Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Self-reported health screening accurately identifies participants without chronic health conditions.
In the paper
“Previous work has found that antibodies and memory B cells correlate for some vaccines or antigens, but do not correlate for many others (34).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > DISCUSSION
What the sources say
- Not checked yetcites [34] I. J. Amanna, N. E. Carlson, M. K. Slifka, Duration of humoral immunity to common viral and vaccine antigens. N. Engl. J. Med. 357, 1903– 1915 (2007). 10.1056/NEJMoa066092 17989383 source
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In the paper
“there are many scenarios where circulating antibodies may not achieve sterilizing immunity and additional immune responses from memory cells will be necessary (36).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > DISCUSSION
What the sources say
- Not checked yetcites [36] M. M. Rosado, M. Scarsella, E. Pandolfi, S. Cascioli, E. Giorda, P. Chionne, E. Madonne, F. Gesualdo, M. Romano, C. M. Ausiello, M. Rapicetta, A. R. Zanetti, A. Tozzi, R. Carsetti, Switched memory B cells maintain specific memory independently of serum antibodies: The hepatitis B example. Eur. J. Immunol. 41, 1800– 1808 (2011). 10.1002/eji.201041187 21469123 source
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In the paper
“All tests were performed two-sided with a nominal significance threshold of p < 0.05.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Data Visualization and Statistics
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In the paper
“In all cases of multiple comparisons, adjustment was performed using Holm correction.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Data Visualization and Statistics
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In the paper
“FRNT50 titers for each sample were measured in at least two technical replicates and were reported for each sample as the geometric mean of the technical replicates.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > SARS-CoV-2 Neutralization Assay
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In the paper
“Standardized SPHERO rainbow beads (Spherotech) were used to track and adjust photomultiplier tubes over time.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Flow Cytometry and Cell Sorting
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In the paper
“For comparisons between timepoints, unpaired tests were used due to missing data/samples for some participants.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Data Visualization and Statistics
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In the paper
“Within each lineage, sequences with fewer than ten copies across all samples in a donor were excluded to reduce the effect of sequencing error and improve fidelity.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > B Cell Receptor (BCR) Sequence Analysis
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In the paper
“Antigen-specific gates were set based on healthy donors stained without antigen probes (similar to an FMO control) and were kept the same for all experimental runs.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Flow Cytometry and Cell Sorting
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In the paper
“44 individuals (33 SARS-CoV-2 naïve, 11 SARS-CoV-2 recovered) were consented and enrolled in the study with approval from the University of Pennsylvania Institutional Review Board (IRB# 844642).”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Recruitment and Clinical Sample Collection
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In the paper
“After sequences were collapsed into clones, non-productive sequences and clones with 1 copy number sequences were excluded from all downstream analysis.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > B Cell Receptor (BCR) Sequence Analysis
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In the paper
“UltraComp eBeads (Thermo Fisher) were used for compensation.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > Flow Cytometry and Cell Sorting
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In the paper
“The primer binding region (IMGT nucleotide positions 1-80) was replaced with Ns and sequences beginning after IMGT position 90 were removed to avoid incorrect V-gene calls and skewed SHM analysis.”
§ Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination > MATERIALS AND METHODS > B Cell Receptor (BCR) Sequence Analysis
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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”
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?
In the citing paper
“a study comparing individuals who are SARS-CoV-2 naive and individuals who have recovered from SARS-CoV-2 identified that either prior infection or vaccination with BNT162b2 was able to efficiently prime memory B cell responses, such that the second exposure (first vaccine dose after previous infection or second vaccine dose in individuals who are SARS-CoV-2 naïve) resulted in boosting of memory B”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [86]
In the citing paper
“mRNA vaccines induce robust germinal center responses in humans (14, 15), which result in memory B cells that are specific for both the full-length SARS-CoV-2 spike protein and the spike receptor-binding domain (RBD) (16–18).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [16]
In the citing paper
“As reported previously by our group and others, mRNA vaccines induced robust circulating antibody responses to the SARS-CoV-2 spike protein and spike RBD with distinct patterns of early response in SARS-CoV-2–naïve and –recovered individuals (Fig. 1B) (16, 34–36).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [16]
In the citing paper
“Consistent with previous reports5–8, vaccination increased the plasma RBD antibody levels, with IgG titres increasing by nearly 30-fold compared with unvaccinated individuals (Fig. 1a, right).”
From Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection (2021) · cites this paper as [5]
In the citing paper
“By contrast, and consistent with previous reports5,8,20, individuals who recovered from COVID-19 and received mRNA vaccines showed an average increase of 8.6-fold in the number of circulating RBD-specific memory B cells (Fig. 2a).”
From Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection (2021) · cites this paper as [5]
In the citing paper
“Vaccination boosts the neutralizing response by 1.5 orders of magnitude by inducing additional plasma cell differentiation from the memory B cell compartment5,7,35.”
From Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection (2021) · cites this paper as [5]
In the citing paper
“The neutralization data reported here are in line with previous reports (42, 47–49).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [42]
In the citing paper
“In line with previous studies (42), a single vaccination led to a rapid and strong recall response in COVID-19–recovered participants, without detectable boosting after the second dose.”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [42]
In the citing paper
“Concerning neutralization of VOCs, recent studies have consistently reported lower neutralizing antibody titers against B.1.351 after vaccination but not against B.1.1.7 (39, 42, 48–59).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [42]
In the citing paper
“Recent studies have documented strong memory B cell and antibody responses post-vaccination that neutralize SARS-CoV-2, including variants of concern (VOCs) such as B.1.351 (Beta) (Goel et al., 2021; Krammer et al., 2021; Sahin et al., 2020; Widge et al., 2021).”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Goel et al., 2021
In the citing paper
“This observation may be noteworthy given the gradual development of antigen-specific CD8+ T cells observed here and the previous observations for humoral responses (Goel et al., 2021; Jackson et al., 2020), which only consistently reach maximal levels after the second vaccine dose.”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Goel et al., 2021
In the citing paper
“These data point to the early induction of antigen-specific CD4+ T cells as a possible contributor to the protection observed in clinical trials as early as two weeks after the first vaccine dose (Baden et al., 2021; Polack et al., 2020), when neutralizing antibody titers are still low in many individuals (Goel et al., 2021).”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Goel et al., 2021
In the citing paper
“These studies have found that vaccination with a single dose of mRNA vaccine is sufficient to boost responses in previously infected individuals (and indeed a second dose has minimal effect).28, 29”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [29]
In the citing paper
“Aggregating these studies, we found that vaccination of convalescent individuals led to 2–10-fold higher neutralisation titres than that seen in naive individuals after primary vaccination (figure 3 ; appendix p 19)26, 27, 28, 29, 30, 31”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [29]
In the citing paper
“and improved cross-reactivity to variants.27, 28, 29, 30”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [29]
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
MajorThe 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.
“only 4/25 individuals developing neutralizing titers above limit of detection over the same time frame”
“only 2/25 had neutralizing antibodies to the B.1.351 variant after the first dose of vaccine”
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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
- ORCID
- Goel, Rishi R.
- Apostolidis, Sokratis A.
- Painter, Mark M.
- Mathew, Divij
- Pattekar, Ajinkya
- Kuthuru, Oliva
- Gouma, Sigrid
- Hicks, Philip
- Meng, Wenzhao
- Rosenfeld, Aaron M.
- Dysinger, Sarah
- Lundgreen, Kendall A.
- Kuri-Cervantes, Leticia
- Adamski, Sharon
- Hicks, Amanda
- Korte, Scott
- Oldridge, Derek A.
- Baxter, Amy E.
- Giles, Josephine R.
- Weirick, Madison E.
- McAllister, Christopher M.
- Dougherty, Jeanette
- Long, Sherea
- D’Andrea, Kurt
- Hamilton, Jacob T.
- Betts, Michael R.
- Luning Prak, Eline T.
- Bates, Paul
- Hensley, Scott E.
- Greenplate, Allison R.
- Wherry, E. John
- Venue
- Science Immunology
- Published
- 2021-04-02
- Volume
- 6
- Issue
- 58
- ISSN
- 2470-9468 (ISSN-L)
- PMC
- PMC8158969
- 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
- hybrid
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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