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.
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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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- Findingown data
In SARS-CoV-2 recovered individuals, antibody responses were significantly boosted after the first vaccine dose.
“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).”
Quote in the paperSubstantial claim - Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
- Findingown data
At baseline, SARS-CoV-2 naïve individuals had undetectable levels of IgG antibodies specific for full-length spike protein and the spike RBD.
“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).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve individuals, two vaccine doses are required for optimal neutralizing titers against the B.1.351 variant.
“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).”
Quote in the paperSubstantial claim - Also stated in: § Antibody responses to SARS-CoV-2 mRNA vaccination · plain
- Findingown data
In SARS-CoV-2 recovered individuals, robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells.
“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.”
Quote in the paperSubstantial claim - Also stated in: § Relationships between antibody and memory B cell responses to SARS-CoV-2 mRNA vaccination · boosted
- Findingown data
In SARS-CoV-2 naïve individuals, the memory B cell response declined slightly with age.
“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).”
Quote in the paperNot a substantial claim - Also stated in: § Demographic and clinical factors associate with B cell responses to SARS-CoV-2 mRNA vaccination · boosted
- Findingown data
In SARS-CoV-2 naïve individuals, memory B cells specific for full-length spike protein and the spike RBD were efficiently primed by mRNA vaccination and detectable in all subjects after the second vaccine dose.
“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).”
Quote in the paperSubstantial claim - Also stated in: § Memory B Cell responses to SARS-CoV-2 mRNA vaccination · plain
- Findingown data
In SARS-CoV-2 recovered individuals, there was no additional increase in antibody levels after the second vaccine dose.
“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.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In SARS-CoV-2 recovered individuals, SHM levels in pre-existing spike-binding clones that were shared between baseline and at least one other timepoint did not increase after vaccination.
“SHM levels in the overlapping clones did not increase after vaccination (Fig. 2F).”
Quote in the paperSubstantial claim - Findingown data
Pre-existing memory B cells in SARS-CoV-2 recovered subjects correlated strongly with post-vaccination antibody levels in our cohort.
“Indeed, pre-existing memory B cells in SARS-CoV-2 recovered subjects correlated strongly with post-vaccination antibody levels in our cohort”
Quote in the paperSubstantial claim- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Findingown data
In SARS-CoV-2 naïve vaccinees, there was no trend toward an increase in memory B cell response with systemic side effects.
“Such a trend was not observed for the memory B cell response (Fig. 3E).”
Quote in the paperNot a substantial claim - Findingown data
Anti-RBD IgG levels were similar in SARS-CoV-2 naïve and recovered individuals at 1 week post-boost.
“Notably, the levels of anti-RBD IgG were similar in the SARS-CoV-2 naïve and SARS-CoV-2 recovered individuals at 1 week post-boost (timepoint 4) (Fig. 1B).”
Quote in the paperSubstantial claim - Findingown data
All SARS-CoV-2 recovered individuals had detectable levels of anti-spike and anti-RBD IgG at baseline.
“In contrast, all SARS-CoV-2 recovered individuals had detectable levels of anti-spike and anti-RBD IgG at baseline, and these antibody responses were significantly increased after the first dose of vaccine (Fig. 1B).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 recovered individuals, pre-vaccine baseline antibody levels did not correlate with baseline memory B cell frequencies.
“Similarly, pre-vaccine baseline antibody levels did not correlate with baseline memory B cell frequencies in SARS-CoV-2 recovered individuals (figure S5A).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve individuals, antibodies and memory B cells clustered separately.
“Hierarchical clustering of the different readouts of antigen-specific humoral immunity also revealed that antibodies and memory B cells clustered separately (Fig. 4A).”
Quote in the paperSubstantial claim - Findingown data
SARS-CoV-2 naïve individuals had minimal spike-specific memory B cells at baseline.
“Consistent with the antibody data, SARS-CoV-2 naïve individuals had minimal spike-specific memory B cells at baseline, whereas SARS-CoV-2 recovered individuals had a significant population of spike-specific memory B cells ranging from ~0.15-0.8% of total memory B cells (Fig. 2A-B).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve individuals, the fraction of the overall spike-specific memory B cell response focused on RBD increased over time, becoming equivalent to that observed in SARS-CoV-2 recovered individuals after the second vaccine dose.
“In SARS-CoV-2 naïve subjects, the fraction of the overall spike-specific memory B cell response that was focused on RBD increased over time, becoming equivalent to that observed in SARS-CoV-2 recovered individuals after the second vaccine dose (Fig. 2D).”
Quote in the paperSubstantial claim - Findingown data
SARS-CoV-2 recovered individuals had a significant population of spike-specific memory B cells at baseline, ranging from ~0.15-0.8% of total memory B cells.
“whereas SARS-CoV-2 recovered individuals had a significant population of spike-specific memory B cells ranging from ~0.15-0.8% of total memory B cells (Fig. 2A-B).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve individuals, the frequency of IgG+ memory B cells increased to >50% following the second dose.
“The frequency of IgG+ memory B cells increased to >50% following the second dose of vaccine in these subjects (Fig. 2C), consistent with a qualitative improvement in memory B cells after the boost.”
Quote in the paperSubstantial claim - Findingown data
All subjects, regardless of age, had significant humoral and memory B cell responses to vaccination.
“Although all subjects, regardless of age, had significant humoral and memory B cell responses to vaccination, these data highlight a need to further understand the age-related changes in responses to mRNA vaccination (33).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, antibody and memory B cell measurements had distinct contributions to the first 2 principal components.
“Antibody and memory B cell measurements had distinct contributions to the first 2 principal components, with total binding antibodies and neutralizing titers primarily contributing to dimension 1 (Dim1) and memory cells primarily contributing to dimension 2 (Dim2) (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data
There was no relationship between post-vaccination serum antibody levels and memory B cells in SARS-CoV-2 naïve subjects.
“Specifically, we found no relationship between post-vaccination serum antibody levels and memory B cells in SARS-CoV-2 naïve subjects”
Quote in the paperSubstantial claim- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Findingown data
In SARS-CoV-2 naïve vaccinees, multivariate analysis revealed a positive association of systemic side effects with anti-spike and anti-RBD antibody levels 7 days after booster immunization.
“This multivariate analysis similarly revealed a positive association of systemic side effects with anti-spike and anti-RBD antibody levels 7 days after the booster immunization (Fig. 3F).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees with systemic side effects following the second dose, there was a trend toward an increase in antibody responses at the post-boost timepoint.
“In SARS-CoV-2 naïve vaccinees with systemic side-effects following the second dose, there was a trend toward an increase in antibody responses at the post-boost timepoint (Fig. 3E).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, primary immunization significantly increased spike-specific and RBD-specific memory B cells over baseline.
“After primary immunization, SARS-CoV-2 naïve individuals had a significant increase in spike-specific and RBD-specific memory B cells over baseline (Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve individuals, pre-boost anti-RBD antibodies were more predictive of neutralization titers against D614G and B.1.351 than anti-spike antibodies.
“Pre-boost anti-RBD antibodies were more predictive of neutralization titers against D614G and B.1.351 (Fig. 1E) than anti-spike antibodies.”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees, there was a trend toward a negative relationship between age and pre-boost RBD-specific IgG.
“While there was no association between age and anti-spike IgG after the first immunization (i.e., pre-boost), there was a trend toward a negative relationship between age and pre-boost RBD-specific IgG (Fig. 3C).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees, all age groups displayed an increase in the frequency of SARS-CoV-2 specific memory B cells compared to pre-vaccine baseline.
“Although this relationship represented weaker induction of memory B cells with older age, all age groups still displayed an increase in the frequency of SARS-CoV-2 specific memory B cells compared to pre-vaccine baseline (Fig. 3C-D).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees, there was no change in the frequency of total memory B cells by sex or age.
“There was also no change in the frequency of total memory B cells by sex or age, indicating the antigen-specific nature of this effect (figure S4).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees, there was a clear negative correlation between the post-boost frequency of antigen-specific memory B cells and age.
“However, there was a clear negative correlation between the post-boost frequency of antigen-specific memory B cells and age (Fig. 3D).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 recovered donors, baseline levels of SARS-CoV-2-specific antibody correlated with the level of anti-spike, but not anti-RBD, antibody achieved after primary vaccine.
“Interestingly, the baseline levels of SARS-CoV-2-specific antibody correlated with the level of anti-spike, but not anti-RBD antibody achieved after primary vaccine in SARS-CoV-2 recovered donors (figure S5B).”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees, there was no association between age and anti-spike IgG after the first immunization.
“While there was no association between age and anti-spike IgG after the first immunization (i.e., pre-boost), there was a trend toward a negative relationship between age and pre-boost RBD-specific IgG (Fig. 3C).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, spike- and RBD-specific antibody levels appeared to plateau between the first and second doses before increasing again following booster vaccination.
“however, the spike- and RBD-specific antibody levels appeared to plateau between the first and second doses of vaccine before increasing again following booster vaccination.”
Quote in the paperSubstantial claim - Findingown data
Analysis of bulk B cell populations revealed no change in the frequency of naïve, non-naïve, or memory B cells across the vaccination timecourse or between SARS-CoV-2 naïve and recovered individuals.
“Analysis of bulk B cell populations revealed no change in the frequency of naïve, non-naïve, or memory B cells across the timecourse of vaccination, or between SARS-CoV-2 naïve and recovered individuals (figure S2B), highlighting the stability of the overall B cell compartment.”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, primary immunization induced detectable neutralizing antibodies against D614G in approximately 50% of participants.
“SARS-CoV-2 naïve individuals had a moderate response to primary immunization with ~50% of participants developing detectable levels of neutralizing antibodies against D614G two weeks post-primary (Fig. 1C-D).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, both anti-spike and anti-RBD antibodies correlated more strongly with neutralizing titers against D614G and B.1.351 after the second dose than before.
“Both anti-spike and anti-RBD antibodies correlated more strongly with neutralizing titers against D614G and B.1.351 after the second dose (Fig. 1E), indicating a marked improvement in the quality of the antibody response.”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2 naïve vaccinees, antibody for both spike and RBD had a negative but statistically insignificant correlation with age after the second vaccine dose.
“Antibody for both spike and RBD had a similarly negative, but statistically insignificant, correlation with age after the second vaccine dose (Fig. 3C).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 recovered individuals, ~60-70% of spike-specific memory B cells detected prior to vaccination were IgG+.
“Conversely, in SARS-CoV-2 recovered individuals, ~60-70% of spike-specific memory B cells detected prior to vaccination were IgG+ (Fig. 2C).”
Quote in the paperSubstantial claim - Findingown data
We find associations of vaccine-induced immune responses with age and side effects.
“We also find associations of vacccine-induced immune responses with age and side effects”
Quote in the paperNot a substantial claim- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Findingown data
In SARS-CoV-2 recovered individuals, baseline frequency of antigen-specific memory B cells strongly correlated with post-primary vaccination antibody levels for both spike and RBD.
“However, 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.”
Quote in the paperSubstantial claim - Findingown data
Our analysis of antibodies and cellular memory reveals distinct responses to SARS-CoV-2 mRNA vaccines based on prior history of infection.
“our analysis of antibodies and cellular memory reveals distinct responses to SARS-CoV-2 mRNA vaccines based on prior history of infection.”
Quote in the paperSubstantial claim- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Findingown data
In SARS-CoV-2 naïve vaccinees, there were no associations between sex and antibody or memory B cell responses.
“In our cohort of SARS-CoV-2 naïve vaccinees, there were no associations between sex and antibody or memory B cell responses (Fig. 3A, 3B).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, post-boost samples clustered away from earlier timepoints.
“As expected, post-boost (timepoint 4) samples clustered away from the earlier timepoints, with some sub-grouping of patients based on the relative magnitude of antibody and memory B cell responses (Fig. 4A).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 recovered individuals, the first vaccine dose resolved baseline differences in neutralization between D614G and B.1.351.
“Interestingly, the first dose of vaccine also appeared to resolve baseline differences in neutralization between D614G and B.1.351 in this group (Fig. 1D).”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2 naïve individuals, the second vaccine dose significantly boosted spike-specific and RBD-specific memory B cells, approaching levels observed in non-vaccinated SARS-CoV-2 recovered donors.
“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).”
Quote in the paperSubstantial claim - Interpretationown data
COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses.
“whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses.”
- Also stated in: § DISCUSSION · hedged
“These data suggest that only a single vaccine dose in individuals confirmed to have previously been infected with SARS-CoV-2 may be enough to induce antibody and memory B cell responses.”
Quote in the paperSubstantial claim- Rests on an assumption: The prior SARS-CoV-2 infection status of recovered individuals is accurately known.
- Also stated in: § DISCUSSION · hedged
- Interpretationown data
Pre-existing memory B cells play a key role in mounting recall antibody responses to SARS-CoV-2 antigens 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 · hedged
“consistent with the notion that these pre-vaccination memory B cells are major contributors to the SARS-CoV-2 antibody recall response.”
Quote in the paperSubstantial claim - Also stated in: § Relationships between antibody and memory B cell responses to SARS-CoV-2 mRNA vaccination · hedged
- Interpretationown data
If circulating antibodies wane over time, durable memory B cells are likely to provide a rapid source of protective antibody upon SARS-CoV-2 re-exposure.
“if circulating antibodies wane over time, our data suggest that durable memory B cells are likely to provide a rapid source of protective antibody upon SARS-CoV-2 re-exposure.”
Quote in the paperSubstantial claim- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Study design and conductreasoning
The study size, designed for deep immunological analysis, could not directly address protection or true vaccine efficacy.
“However, with a study of this size designed for deep immunological analysis, it was not possible to directly address protection or true vaccine efficacy.”
Quote in the paperSubstantial claim - Study design and conductown data
The cohort consisted of individuals who were not hospitalized during their SARS-CoV-2 infections.
“Our cohort also consisted of individuals who were not hospitalized during their SARS-CoV-2 infections, and it may be necessary to address this question of one versus two doses of vaccine in individuals who experienced more severe COVID-19.”
Quote in the paperNot a substantial claim - Interpretationown data
A two-dose mRNA vaccine schedule is needed in SARS-CoV-2 naïve individuals to achieve optimal levels of humoral immunity, including neutralizing antibodies against the B.1.351 variant.
“Together, these data are consistent with the need for a two dose mRNA vaccine schedule in SARS-CoV-2 naïve individuals to achieve optimal levels of humoral immunity, including neutralizing antibodies against the B.1.351 variant.”
Quote in the paperSubstantial claim - Study design and conductcitation
The estimated specificity of the SARS-CoV-2-specific antibody ELISA is 98.9% (95% CI, 98.0 to 99.5%).
“The estimated sensitivity of the test is 100% [95% confidence interval (CI), 89.1 to 100.0%], and the specificity is 98.9% (95% CI, 98.0 to 99.5%) (45).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] D. D. Flannery, S. Gouma, M. B. Dhudasia, S. Mukhopadhyay, M. R. Pfeifer, E. C. Woodford, J. S. Gerber, C. P. Arevalo, M. J. Bolton, M. E. Weirick, E. C. Goodwin, E. M. Anderson, A. R. Greenplate, J. Kim, N. Han, A. Pattekar, J. Dougherty, O. Kuthuru, D. Mathew, A. E. Baxter, L. A. Vella, J. Weaver, A. Verma, R. Leite, J. S. Morris, D. J. Rader, M. A. Elovitz, E. J. Wherry, K. M. Puopolo, S. E. Hensley, SARS-CoV-2 seroprevalence among parturient women in Philadelphia. Sci. Immunol. 5, eabd5709 (2020). 10.1126/sciimmunol.abd5709 32727884 PMC7594018 source
Not checked in the free run.
- Interpretationown data
Age is a key variable in mRNA vaccine-induced immunity.
“However, the magnitude of the memory B cell response following the second dose was lower with increased age, confirming age as a key variable in mRNA vaccine-induced immunity.”
Quote in the paperSubstantial claim - Interpretationown data
Pre-vaccination memory B cells are major contributors to the SARS-CoV-2 antibody recall response in recovered individuals.
“consistent with the notion that these pre-vaccination memory B cells are major contributors to the SARS-CoV-2 antibody recall response.”
Quote in the paperSubstantial claim - Interpretationown data
Pre-existing spike-specific memory clones in SARS-CoV-2 recovered individuals did not increase their level of SHM in response to either dose of vaccine.
“These data suggested that pre-existing spike-specific memory clones in SARS-CoV-2 recovered individuals did not increase their level of SHM in response to either dose of vaccine.”
Quote in the paperSubstantial claim- 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.
- Interpretationown data
Short-term serological responses and memory B cell responses may be distinct immunological features of response to mRNA vaccination.
“indicating that short-term serological responses and memory B cell responses may be distinct immunological features of response to mRNA vaccination.”
Quote in the paperSubstantial claim - Study design and conductcitation
The estimated sensitivity of the SARS-CoV-2-specific antibody ELISA is 100% (95% CI, 89.1 to 100.0%).
“The estimated sensitivity of the test is 100% [95% confidence interval (CI), 89.1 to 100.0%], and the specificity is 98.9% (95% CI, 98.0 to 99.5%) (45).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] D. D. Flannery, S. Gouma, M. B. Dhudasia, S. Mukhopadhyay, M. R. Pfeifer, E. C. Woodford, J. S. Gerber, C. P. Arevalo, M. J. Bolton, M. E. Weirick, E. C. Goodwin, E. M. Anderson, A. R. Greenplate, J. Kim, N. Han, A. Pattekar, J. Dougherty, O. Kuthuru, D. Mathew, A. E. Baxter, L. A. Vella, J. Weaver, A. Verma, R. Leite, J. S. Morris, D. J. Rader, M. A. Elovitz, E. J. Wherry, K. M. Puopolo, S. E. Hensley, SARS-CoV-2 seroprevalence among parturient women in Philadelphia. Sci. Immunol. 5, eabd5709 (2020). 10.1126/sciimmunol.abd5709 32727884 PMC7594018 source
Not checked in the free run.
- Interpretationown data
A 2-dose regimen is important for effective antibody responses, especially against the B.1.351 variant, in SARS-CoV-2 naïve individuals.
“Together, these data supported the importance of a 2 dose-regimen for effective antibody responses, especially against the B.1.351 variant, in SARS-CoV-2 naïve individuals.”
Quote in the paperSubstantial claim - Interpretationown data
The second dose of mRNA vaccine improved the quality of the antibody response in SARS-CoV-2 naïve individuals.
“indicating a marked improvement in the quality of the antibody response.”
Quote in the paperSubstantial claim - Interpretationown data
There is an immunological connection between memory B cells and antibody recall responses.
“underscoring the immunological connection between memory B cells and antibody recall responses (35).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] M. McHeyzer-Williams, S. Okitsu, N. Wang, L. McHeyzer-Williams, Molecular programming of B cell memory. Nat. Rev. Immunol. 12, 24– 34 (2011). 10.1038/nri3128 22158414 PMC3947622 source
Not checked in the free run.
- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Interpretationown data
Antibody and memory B cell induction may be independent features of the immune response to mRNA vaccination.
“indicating that antibody and memory B cell induction may be independent features of the immune response to mRNA vaccination.”
Quote in the paperSubstantial claim- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- Interpretationown data
The addition of memory B cells in this analysis, both in terms of frequency and phenotype, provides complementary data that strengthens current serology-based evidence for a single-dose vaccine schedule in COVID-19 recovered individuals.
“The addition of memory B cells in this analysis, both in terms of frequency and phenotype, provides complemenary data that strengthens current serology-based evidence (20, 21, 23, 24, 28, 29) for a single-dose vaccine schedule in COVID-19 recovered individuals.”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [20] F. Krammer, K. Srivastava, P. Team, V. Simon, H. Alshammary, A. Amoako, M. Awawda, K. Beach, C. M. Bermúdez-González, D. Bialak, J. M. Carreño, R. Chernet, L. Eaker, E. Ferreri, D. Floda, C. Gleason, J. Hamburger, K. Jiang, G. D. Kleiner, J. Jurczyszak, W. Matthews, L. Mendez, I. Mulder, A. Nabeel, K. Raskin, A. Russo, M. Salimbangon, A. Saksena, G. Shin, L. Singh, D. Sominsky, medRxiv, in press, doi:. 10.1101/2021.01.29.21250653
Not checked in the free run.
- cites [21] S. Saadat, Zahra, R. Tehrani, J. Logue, M. Newman, M. B. Frieman, A. D. Harris, M. M. Sajadi, medRxiv, in press, doi:. 10.1101/2021.01.30.21250843
Not checked in the free run.
- cites [23] M. I. Samanovic, A. R. Cornelius, J. P. Wilson, T. Karmacharya, S. L. Gray-Gaillard, J. R. Allen, S. W. Hyman, G. Moritz, M. Ali, S. B. Koralov, M. J. Mulligan, R. S. Herati, Poor antigen-specific responses to the second BNT162b2 mRNA vaccine dose in SARS-CoV-2-experienced individuals. medRxiv 2021.02.07.21251311 (2021). 10.1101/2021.02.07.21251311 33594383 PMC7885942
Not checked in the free run.
- cites [24] L. Stamatatos, J. Czartoski, Y.-H. Wan, L. J. Homad, V. Rubin, H. Glantz, M. Neradilek, E. Seydoux, M. F. Jennewein, A. J. MacCamy, J. Feng, G. Mize, S. C. De Rosa, A. Finzi, M. P. Lemos, K. W. Cohen, Z. Moodie, M. J. McElrath, A. T. McGuire, A single mRNA immunization boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. medRxiv 2021.02.05.21251182, in press (2021). 10.1101/2021.02.05.21251182 33766944 PMC8139425
Not checked in the free run.
- cites [28] 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 1 2. medRxiv, 4 (2021).
Not checked in the free run.
- cites [29] K. Abu Jabal, H. Ben-Amram, K. Beiruti, Y. Batheesh, C. Sussan, S. Zarka, M. Edelstein, Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers, Israel, December 2020 to January 2021. Euro Surveill. 26, 2100096 (2021). 10.2807/1560-7917.ES.2021.26.6.2100096 33573712 PMC7879501 source
Not checked in the free run.
- Rests on an assumption: Pfizer BNT162b2 and Moderna mRNA-1273 vaccines can be grouped together as mRNA vaccination for the analyses.
- May combine two claims. 13
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 18
May combine two claims.
Findingown datamRNA vaccines induced robust serological and cellular priming.
“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.”
Quote in the paperSubstantial claim- 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
May combine two claims.
Findingown dataIn SARS-CoV-2 naïve individuals, primary vaccination induced a significant increase in SARS-CoV-2-specific antibodies, and the booster dose further enhanced this increase.
“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.”
Quote in the paperSubstantial claim- Also stated in: § Abstract · plain
May combine two claims.
Findingown dataIn SARS-CoV-2 recovered individuals, antigen-specific memory B cells were significantly boosted after the first dose, with no additional increase after the second dose.
“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).”
Quote in the paperSubstantial claim- Also stated in: § Memory B Cell responses to SARS-CoV-2 mRNA vaccination · plain
May combine two claims.
Findingown dataIn SARS-CoV-2 recovered individuals, neutralizing titers were significantly increased after the first dose, with no further increase after the second dose.
“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.”
Quote in the paperSubstantial claim- Also stated in: § DISCUSSION · plain
May combine two claims.
Findingown dataIn SARS-CoV-2 recovered individuals, the frequency of IgG+ memory B cells increased slightly to ~75% following the first dose, with no further increases after the second immunization.
“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).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataVaccine-induced side effects may be related to post-vaccination serum antibodies, but not memory B cells.
“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.”
Quote in the paperNot a substantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataInfluenza HA-specific memory B cells remained stable throughout the mRNA vaccination timecourse in both SARS-CoV-2 naïve and recovered individuals, confirming the specificity of the memory B cell assay.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn SARS-CoV-2 naïve individuals, ~25-30% of spike-specific memory B cells were IgG+ and ~40-50% were IgM+ on day 15 after primary immunization.
“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).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataOne self-reported naïve subject 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.
“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.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningAll timepoints for individual subjects were run in the same experiment to minimize batch effects.
“All timepoints for individual subjects were run in the same experiment to minimize batch effects.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductcitationTimepoints were chosen a priori to capture the peak antigen-specific response for primary and secondary responses in SARS-CoV-2 naïve individuals.
“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.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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
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- cites [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 in the free run.
- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenTwo biological replicates were run on all samples for BCR sequencing.
“Two biological replicates were run on all samples.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataA single dose of vaccine achieved highly effective antibody responses in SARS-CoV-2 recovered individuals with no further improvement post-boost.
“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.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataAll participants were otherwise healthy and based on self-reported health screening did not report any history of chronic health conditions.
“All participants were otherwise healthy and based on self-reported health screening did not report any history of chronic health conditions.”
Quote in the paperNot a substantial claim- Rests on an assumption: Self-reported health screening accurately identifies participants without chronic health conditions.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPrevious work has found that antibodies and memory B cells correlate for some vaccines or antigens, but do not correlate for many others.
“Previous work has found that antibodies and memory B cells correlate for some vaccines or antigens, but do not correlate for many others (34).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThere are many scenarios where circulating antibodies may not achieve sterilizing immunity and additional immune responses from memory cells will be necessary.
“there are many scenarios where circulating antibodies may not achieve sterilizing immunity and additional immune responses from memory cells will be necessary (36).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll tests were performed two-sided with a nominal significance threshold of p < 0.05.
“All tests were performed two-sided with a nominal significance threshold of p < 0.05.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenIn all cases of multiple comparisons, adjustment was performed using Holm correction.
“In all cases of multiple comparisons, adjustment was performed using Holm correction.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataFRNT50 titers for each sample were measured in at least two technical replicates and reported as the geometric mean of the technical replicates.
“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.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenStandardized SPHERO rainbow beads were used to track and adjust photomultiplier tubes over time.
“Standardized SPHERO rainbow beads (Spherotech) were used to track and adjust photomultiplier tubes over time.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataFor comparisons between timepoints, unpaired tests were used due to missing data/samples for some participants.
“For comparisons between timepoints, unpaired tests were used due to missing data/samples for some participants.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningWithin 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.
“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.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenAntigen-specific gates were set based on healthy donors stained without antigen probes and were kept the same for all experimental runs.
“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.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe study was approved by the University of Pennsylvania Institutional Review Board (IRB# 844642).
“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).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAfter sequences were collapsed into clones, non-productive sequences and clones with 1 copy number sequences were excluded from all downstream analysis.
“After sequences were collapsed into clones, non-productive sequences and clones with 1 copy number sequences were excluded from all downstream analysis.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenUltraComp eBeads were used for compensation.
“UltraComp eBeads (Thermo Fisher) were used for compensation.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningThe 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.
“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.”
Quote in the paperSubstantial claim
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?
Prior infection or BNT162b2 vaccination efficiently primes memory B cell responses, so that a second exposure boosts those memory B cell responses.
“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]
mRNA vaccines induce robust germinal center responses in humans, resulting in memory B cells specific for full-length spike and RBD.
“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]
mRNA vaccines induced robust circulating antibody responses to SARS-CoV-2 spike protein and spike RBD, with distinct early response patterns in naïve and recovered individuals.
“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]
Vaccination increased plasma RBD antibody levels in convalescent individuals, with IgG titres increasing by nearly 30-fold compared with unvaccinated individuals.
“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]
Convalescent individuals who received mRNA vaccines showed an average increase of 8.6-fold in the number of circulating RBD-specific memory B cells.
“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]
Vaccination boosts the neutralizing response by 1.5 orders of magnitude by inducing additional plasma cell differentiation from the memory B cell compartment.
“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]
The neutralization data reported here are in line with previous reports.
“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]
A single vaccination led to a rapid and strong recall response in COVID-19-recovered participants, without detectable boosting after the second dose.
“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]
Recent studies have consistently reported lower neutralizing antibody titers against B.1.351 after vaccination but not against B.1.1.7.
“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]
Prior work reports that vaccination generates memory B cells and antibodies that neutralize SARS-CoV-2, including variants like B.1.351.
“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
Humoral responses only consistently reach maximal levels after the second vaccine dose.
“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
Two weeks after the first vaccine dose, neutralizing antibody titers remain low in many individuals.
“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
Vaccination with a single dose of mRNA vaccine is sufficient to boost neutralising antibody responses in previously infected individuals, and a second dose has minimal additional effect.
“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]
Vaccination of convalescent individuals led to 2-10-fold higher neutralisation titres than naive individuals after primary vaccination.
“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]
Vaccination of convalescent individuals improved cross-reactivity to variants.
“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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- 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.
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