BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans

May combine two claims.

The US trial elicited robust S1-binding IgG concentrations and neutralizing titres against wild-type Wuhan-Hu-1 SARS-CoV-2.

“Robust concentrations of S1-binding immunoglobulin G (IgG) and neutralizing titres against a SARS-CoV-2 strain with the wild-type (Wuhan-Hu-1) S sequence were elicited.”

• cites [2] Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020). sourcePartly supported

  The Immunogenicity section (page unavailable) reports boosted antigen-binding IgG and neutralizing responses in the US trial; Figure 4 identifies the IgG measure as S1-binding. The methods identify the neutralization-test strain as USA_WA1/2020, but our copy does not establish that it had the wild-type Wuhan-Hu-1 S sequence. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Both BNT162b1 and BNT162b2 are pharmacologically optimized N1-methylpseudouridine nucleoside-modified mRNAs given intramuscularly in a prime-boost regimen.

“Both of the candidates are pharmacologically optimized 15,16 , N 1 -methylpseudouridine nucleoside-modified mRNAs 17 that are administered intramuscularly in a prime-boost regimen 21”

• cites [15] Holtkamp, S. et al. Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells. Blood 108, 4009–4017 (2006). sourceSupported
• cites [16] Orlandini von Niessen, A. G. et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3′ UTRs identified by cellular library screening. Mol. Ther. 27, 824–836 (2019). sourceNot checked — no full text of the source
• cites [17] Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008). sourcePartly supported

  The Results and Materials and Methods describe pseudouridine-modified mRNA, and the Results report improved translation. They do not identify or test N1-methylpseudouridine, the specific modification attributed to this source by citation 17. The vaccine identities and prime-boost regimen are attached to other citations in the sentence. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [21] Taylor, D. N. et al. Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response. Vaccine 30, 5761–5769 (2012). sourceNot checked — no full text of the source

May combine two claims.

BNT162b2 demonstrated 95% efficacy against COVID-19 in a phase-II/III trial, and real-world data confirm it is highly effective at preventing COVID-19, hospitalization and death from SARS-CoV-2 infection.

“The vaccine showed 95% efficacy for protection against COVID-19 in a phase-II/III trial 1 and emerging real-world data confirm that BNT162b2 is highly effective in preventing COVID-19 and hospitalization and death associated with SARS-CoV-2 infection [3][4][5] .”

• cites [1] Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020). sourceSupported
• cites [3][4][5]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Seven days after a 30-μg booster, sera from younger (18-55 years) and older (65-85 years) adults had 50% neutralizing GMTs 3.8-fold and 1.6-fold the GMT of COVID-19 convalescent samples, respectively.

“Geometric mean 50% neutralizing titres (GMTs) of sera drawn from younger (18-55 years) and older (65-85 years) adults seven days after the booster dose of 30 μg BNT162b2 were 3.8-fold and 1.6-fold, respectively, the GMT of samples from individuals who had recovered from COVID-19.”

• cites [2] Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020). sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

mRNA production and lipid nanoparticle formulation are fast and highly scalable, making the technology suitable for rapid vaccine development and supply during pandemics.

“mRNA production and lipid nanoparticle formulation are fast and highly scalable, which renders this technology suitable for the rapid development and supply of vaccines during pandemic scenarios 11,12 .”

• cites [11] Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines – a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018). sourcePartly supported

  The Good manufacturing practice production section says mRNA can be produced rapidly in a small facility and is suitable for rapid response to emerging infectious diseases; the Abstract describes its manufacturing as potentially scalable. The Progress in mRNA vaccine delivery section identifies lipid nanoparticles as commonly used delivery tools, but the copy does not establish that their formulation is fast and highly scalable. The GMP section also notes that some production components were available only at limited scale, so rapid pandemic-scale supply is not established. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [12] Maruggi, G., Zhang, C., Li, J., Ulmer, J. B. & Yu, D. mRNA as a transformative technology for vaccine development to control infectious diseases. Mol. Ther. 27, 757–772 (2019). sourceNot checked — no full text of the source

May combine two claims.

BNT162b2 uses lipid-nanoparticle-formulated mRNA technology that delivers the immunogen's genetic information to antigen-presenting cells and elicits potent immune responses.

“BNT162b2 is based on lipid-nanoparticle-formulated mRNA vaccine technology, which delivers precise genetic information of the immunogen to antigen-presenting cells and elicits potent immune responses 7 .”

• cites [7] Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571–1588 (2018). sourcePartly supported

  The Results describe lipid-nanoparticle-formulated mRNA producing protein after delivery in mice, and the Discussion reports strong immune responses in mice and rhesus macaques. The Results identify skin antigen-presenting cells as a rationale for the injection site, but do not establish delivery specifically to those cells. The paper studies the vaccine platform, not BNT162b2, so it does not verify the product-specific claim. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

As in the US phase-I/II trial, prime-boost vaccination with 10-30 μg BNT162b2 elicited serum GMTs that after an initial decline remained stable for the entire nine-week post-booster follow-up, at or above the GMTs of COVID-19 convalescent individuals.

“As reported for the phase-I/II trial in the USA 2 , prime-boost vaccination with 10 to 30 μg of BNT162b2 elicited GMTs of sera that-after an initial decline-remained stable for the entire follow-up of nine weeks after the booster dose, in the range of or higher than GMTs in individuals who had recovered from COVID-19.”

• cites [2] Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020). sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

SARS-CoV-2 spike-derived CD8+ T cell epitopes after natural infection, including the immunodominant HLA-A*0201-restricted peptide YLQPRTFLL also identified here, have been published, but this is to our knowledge the first report of epitopes recognized by vaccine-induced T cells.

“Although SARS-CoV-2 S-derived CD8 + T cell epitopes after natural infection have previously been published (including the immunodominant HLA-A*0201-restricted peptide YLQPRTFLL that is also identified in this Article) 37,38 , to our knowledge this is the first report of epitopes recognized by vaccine-induced T cells.”

• cites [37] Xie, X. et al. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat. Med. 27, 620–621 (2021). sourceCould not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [38] O’Toole, Á. et al. Tracking the international spread of SARS-CoV-2 lineages B.1.1.7 and B.1.351/501Y–V2, https://virological.org/t/tracking-the-international-spread-of-sars-cov-2-lineages-b-1–1-7-and-b-1–351–501y-v2/592 (2021). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

To allow comparison with previously reported data on BioNTech-Pfizer RNA COVID-19 vaccines, sera for neutralizing titers were analyzed as previously described.

“To enable the comparison of vaccine-induced serum neutralizing titres to those previously reported for BioNTech-Pfizer RNA vaccines for COVID-19, sera were analysed as previously described 2,13,14 .”

• cites [2] Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020). sourceSupported
• cites [13] Mulligan, M. J. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586, 589–593 (2020). sourceSupported
• cites [14] Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020). sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

To allow comparison with previously reported data on BioNTech-Pfizer RNA COVID-19 vaccines, sera for S1- and RBD-binding IgG were analyzed as previously described.

“To enable the comparison of vaccine-induced S1-and RBD-binding IgG responses to previously reported data on the BioNTech-Pfizer RNA vaccines for COVID-19, sera were analysed as previously described 2,13,14 .”

• cites [2] Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020). sourceSupported
• cites [13] Mulligan, M. J. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586, 589–593 (2020). sourcePartly supported

  The Methods describe how vaccine-induced RBD-binding IgG was measured in sera, and Figure 4 reports those responses. Our copy does not describe an S1-binding IgG assay, so this source supports the RBD part of the cited method but not the S1 part. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [14] Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020). sourcePartly supported

  The RBD-binding IgG assay section describes how the paper analysed participant sera for RBD-binding IgG, supporting the citation as a previously described method. The passages found do not describe an S1-binding IgG assay, so this source alone does not support that part of the sentence. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Among convalescent serum donors, geometric mean neutralizing titers were 90 for symptomatic infections (n=35), 156 for asymptomatic infections (n=3), and 618 for hospitalized individuals (n=1).

“GMTs in subgroups of the donors were as follows: symptomatic infections, 90 (n = 35); asymptomatic infections, 156 (n = 3); hospitalized, 618 (n = 1).”

• cites [2] Walsh, E. E. et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N. Engl. J. Med. 383, 2439–2450 (2020). sourceSupported
• cites [13] Mulligan, M. J. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586, 589–593 (2020). sourcePartly supported

  The Methods section describes 38 convalescent serum donors, including 35 who had symptomatic infections and one who had been hospitalized; the remaining three were asymptomatic. The Immunogenicity section reports a neutralizing GMT of 94 for the panel as a whole, but our copy does not report subgroup GMTs of 90, 156, or 618. Page numbers are not available for these passages. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [14] Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020). sourceSupported

Classified as probably not a substantial claim.

Formation of pMHC complexes was validated in a bead-based flow cytometry assay.

“pMHC complexes were refolded with the easYmer technology (easYmer kit, ImmuneAware Aps), and complex formation was validated in a bead-based flow cytometry assay according to the manufacturer's instructions 49,50 .”

• cites [49] Hadrup, S. R. et al. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat. Methods 6, 520–526 (2009). sourceNot checked — no full text of the source
• cites [50] Katoh, K., Rozewicki, J. & Yamada, K. D. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief. Bioinform. 20, 1160–1166 (2019). sourceCould not verify

  The cited paper’s “MSA of large data” section discusses MAFFT sequence-alignment methods, not pMHC complex formation. Searches for bead-based flow cytometry and easYmer refolding found no passage addressing the claimed validation; no page numbers are available in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Two pseudovirus variants carried either eight or ten mutations found in the S protein of the B.1.351 lineage.

“Two variants had either eight (D80A/D215G/Δ242-244/ K417N/E484K/N501Y/D614G/A701V) or ten mutations (L18F/D80A/ D215G/R246I/Δ242-244/K417N/E484K/N501Y/D614G/A701V) found in S of the B.1.351lineage (also referred to as 20C/501Y.V2) 40 .”

• cites [40] Xie, X. et al. An infectious cDNA clone of SARS-CoV-2. Cell Host Microbe 27, 841–848 (2020). sourceCould not verify

  The Discussion describes an infectious SARS-CoV-2 clone and proposes using it to study future spike mutations; the Methods describe three silent marker mutations. Searches for B.1.351, pseudovirus variants, and the listed spike mutations found no passage in our copy addressing the claimed eight- or ten-mutation variants. The indexed passages provide no page numbers. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

May combine two claims.

Fatigue and headache were the most common systemic adverse events, and only two participants reported mild fever.

“The most common systemic adverse events were fatigue and headache, and only two participants reported mild fever (Extended Data Fig. 2b, Extended Data Table 3b).”

May combine two claims.

After the booster on day 29, neutralizing GMTs rose substantially to 169, 195 or 312 in the 10-, 20- and 30-μg groups, respectively, but only minimally to 25 in the 1-μg group.

“After the booster dose (day 29), GMTs increased substantially to 169, 195 or 312 in participants immunized with 10 μg, 20 μg or 30 μg BNT162b2, respectively, but increased only minimally in participants immunized with 1 μg BNT162b2 (GMT of 25).”

May combine two claims.

On day 85, GMTs ranged from 120 to 181 and were 1.3-1.9 times the GMT of 94 in COVID-19 convalescent individuals.

“At Article day 85, GMTs ranged from 120 to 181, and were 1.3-to 1.9-fold those of individuals who had recovered from COVID-19 (GMT of 94).”

May combine two claims.

By day 22, S1-binding IgG geometric mean concentrations had risen in every dose cohort, ranging from 49 to 1,161 U ml−1.

“On day 22, geometric mean concentrations (GMCs) of S1-binding IgG had increased in all dose cohorts and were in the range of 49 to 1,161 U ml -1 (Extended Data Fig. 4a).”

May combine two claims.

Transient chills were more frequent after the booster, dose-dependent and occasionally severe.

“Transient chills were more common after the boost, were dose-dependent and were occasionally severe.”

May combine two claims.

Local reactions, mainly injection-site pain, were mild to moderate (grades 1-2) and similar in frequency and severity after priming and booster doses.

“Local reactions (predominantly pain at the injection site) were mild-to-moderate (grades 1 and 2) and of similar frequency and severity after the priming and booster doses (Extended Data Fig. 2a, Extended Data Table 3a).”

May combine two claims.

Reactions began within 24 hours of immunization, peaked the next day, mostly resolved within 2-3 days, and either needed no treatment or were managed with simple measures such as paracetamol.

“Reactions had their onset within 24 h of immunization, peaked on the day after immunization and mostly resolved within 2 or 3 days, and either did not require treatment or could be managed with simple measures (such as paracetamol).”

May combine two claims.

Every tested BNT162b2-immune serum neutralized all pseudoviruses, and no pseudovirus escaped neutralization.

“All of the BNT162b2-immune sera that we tested neutralized all the pseudoviruses, and no pseudovirus escaped neutralization.”

May combine two claims.

Most participants mounted strong IFNγ+ or IL-2+ CD8+ and CD4+ Th1 cell responses that remained detectable for the entire nine-week observation period after the booster.

“Most participants had a strong response of IFNγ + or IL-2 + CD8 + and CD4 + T helper type 1 cells, which was detectable throughout the full observation period of nine weeks following the boost.”

May combine two claims.

No related serious adverse events, grade-4 reactions or withdrawals due to related adverse events occurred.

“We observed no related serious adverse events, no grade-4 reactions and no withdrawals owing to related adverse events.”

May combine two claims.

At one week after the booster, epitope-specific CD8+ T cells with an early-differentiated effector-memory phenotype made up 0.02-2.92% of circulating CD8+ T cells and remained detectable at 0.01-0.28% eight weeks later.

“One week after the boost, epitope-specific CD8 + T cells of the early-differentiated effector-memory phenotype comprised 0.02-2.92% of total circulating CD8 + T cells and were detectable (0.01-0.28%) eight weeks later.”

May combine two claims.

A mild drop in blood lymphocyte counts and an increase in C-reactive protein occurred; both were transient, dose-dependent and within or close to normal laboratory levels.

“We observed a mild drop in blood lymphocyte counts and an increase in C-reactive protein, which are known pharmacodynamic markers of mRNA vaccines [19][20][21][22][23] ; both of these were transient, dose-dependent and within, or close to, laboratory-normal levels (Extended Data Fig. 3).”

• cites [19][20][21][22][23]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Muscle and joint pain were also more common after the booster and their severity was dose-dependent.

“Muscle pain and joint pain were also more common after the boost and showed dose-dependent severity.”

May combine two claims.

The other three participants had de novo responses against spike pool 1 and low numbers of pre-existing spike-pool-2-reactive CD4+ T cells.

“The remaining three participants had de novo responses against S pool 1 and low numbers of pre-existing S-pool-2-reactive CD4 + T cells.”

May combine two claims.

Six of those seven participants also had a de novo response to spike pool 1, whose strength did not differ from responses in individuals without pre-existing spike-pool-2 responses.

“Six out of these seven participants had a concurrent de novo response to S pool 1, which did not differ in strength from those responses that we observed in individuals without pre-existing responses to S pool 2 (Extended Data Fig. 5e).”

May combine two claims.

The fraction of vaccine-induced IFNγ- and IL-2-producing T cells rose strongly by day 29, fell until day 43 and then stabilized toward day 85.

“The fraction of IFNγ and IL-2 cytokine-producing T cells induced by the vaccine strongly increased by day 29, declined until day 43 and stabilized towards day 85 (Fig. 3b, Extended Data Fig. 7e).”

May combine two claims.

In 34 of 37 participants (91.9%), most vaccine-induced spike-specific CD8+ T cell responses were strong, with magnitudes comparable to individual memory responses against CMV, EBV and influenza.

“The majority of vaccine-induced S-specific CD8 + T cell responses that we detected in 34 of 37 participants (91.9%) were strong, with magnitudes comparable to individual memory responses against CMV, EBV and influenza virus (Fig. 2a, b, Extended Data Fig. 5a-c).”

May combine two claims.

On day 85, epitope-specific CD8+ T cells were unchanged in participants 1 and 2, while in participant 3 they differentiated toward CD45RA re-expressing cells co-expressing CD27 and CD28.

“On day 85, epitope-specific CD8 + T cells were unchanged in participants 1 and 2 and differentiated towards CD45RA re-expressing cells with CD27 and CD28 co-expression in participant 3”

May combine two claims.

In the B.1.1.298 lineage, which has not shown sustained human-to-human transmission, only one of the eight CD8+ T cell epitopes had a single-point mutation, which may or may not affect MHC binding.

“In the B.1.1.298lineage, which has not demonstrated sustained human-to-human transmission, only one of the eight CD8 + T cell epitopes showed a single-point mutation (which may or may not affect its binding to the respective MHC molecule).”

May combine two claims.

The de novo CD8+ T cell responses targeted both spike pools in 22 participants, spike pool 1 in 10 and spike pool 2 in 2.

“These were directed against both (22 participants) or one of the S pools (S pool 1 in 10 participants and S pool 2 in 2 participants)”

May combine two claims.

T cell response magnitude varied among individuals and, above 1 μg, was independent of dose level.

“The magnitude of the T cell responses varied between individuals and, above a dose level of 1 μg, was independent of dose level.”

May combine two claims.

All evaluable BNT162b2 recipients mounted de novo spike-specific CD4+ T cell responses, and almost 90% mounted de novo CD8+ T cell responses.

“All evaluable participants vaccinated with BNT162b2 mounted de novo S-specific CD4 + T cell responses, and almost 90% of participants mounted de novo CD8 + T cell responses.”

May combine two claims.

Several epitopes were identified for each participant, representing eight distinct epitope-MHC pairs recognized by de novo-induced CD8+ T cells and distributed across the full length of spike.

“We identified several epitopes for each participant, representing eight different epitope-MHC pairs that were recognized by de novo-induced CD8 + T cells and were spread across the full length of S (Fig. 4a, b).”

Probably not a substantial claim: may not pass S3 (load-bearing).

One participant had a strong pre-existing spike-pool-2-specific IFNγ+ CD4+ T cell response.

“We detected a strong pre-existing S-pool-2-specific IFNγ + CD4 + T cell response in one participant (Extended Data Fig. 7b).”

May combine two claims.

The magnitude of spike-specific CD4+ T cell responses correlated positively with S1-binding IgG and with the strength of spike-specific CD8+ T cell responses.

“The magnitude of S-specific CD4 + T cell responses correlated positively with S1-binding IgG (Extended Data Fig. 6a) and, consistent with the concept of intramolecular help 30 , also with the strength of S-specific CD8 + T cell responses (Extended Data Fig. 6b).”

• cites [30] Sette, A. et al. Selective CD4+ T cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities. Immunity 28, 847–858 (2008). sourceNot checked — no full text of the source

May combine two claims.

In agreement with ELISpot results, seven participants had pre-existing spike-pool-2-specific CD8+ T cell responses, and vaccination did not further amplify them in six.

“Confirming ELISpot findings, seven participants displayed pre-existing S-pool-2-specific CD8 + T cell responses, which were not further amplified by vaccination in six participants.”

May combine two claims.

In 30-μg BNT162b2 recipients, both CD4+ and CD8+ T cell responses contracted after day 29 and by day 85 were higher than or similar to recall antigen memory responses.

“Both the CD4 + and the CD8 + T cell responses contracted after day 29 in participants vaccinated with 30 μg BNT162b2, and were higher than or in the range of recall antigen memory responses on day 85 (Fig. 2c, Extended Data Fig. 5f).”

May combine two claims.

A high proportion of boosted CD8+ T cells were early-differentiated central effector and memory cells; the population contracted and further differentiated toward an early-differentiated memory phenotype co-expressing CD27 and CD28.

“A high proportion of boosted CD8 + T cells were early-differentiated central effector and memory cells; the T cell population contracted and further differentiated towards an early-differentiated memory phenotype with co-expression of CD27 and CD28.”

May combine two claims.

Epitope-specific CD8+ T cell responses ranged from 0.02% to 2.92% of peripheral CD8+ T cells, with the largest expansions for HLA-A*0201-YLQPRTFLL, HLA-A*2402-QYIKWPWYI and HLA-B*3501-QPTESIVRF, and contracted to 0.01-0.28% by day 85.

“The magnitude of epitope-specific CD8 + T cell responses ranged from 0.02 to 2.92% of peripheral CD8 + T cells, with the most notable expansion for HLA-A*0201-YLQPRTFLL, HLA-A*2402-QYIKWPWYI and HLA-B*3501-QPTESIVRF, and contracted to 0.01 to 0.28% by day 85.”

May combine two claims.

A considerable fraction of vaccine-induced spike-specific CD4+ T cells secreted IFNγ, IL-2 or both, while IL-4-secreting T cells were barely detected.

“A considerable fraction of vaccine-induced, S-specific CD4 + T cells secreted IFNγ, IL-2 or both, whereas we barely detected T cells secreting the T helper 2 cell cytokine IL-4 (Fig. 3a, Extended Data Fig. 7a-c).”

May combine two claims.

At baseline, CD8+ T cell responses against the S1 subunit were not detected, but several individuals had pre-existing immune responses against the S2 subunit.

“Although CD8 + T cell responses against the S1 subunit were not detected at baseline, several individuals had pre-existing immune responses against the S2 subunit”

May combine two claims.

At doses of 10 μg or higher, the magnitude of CD4+ T cell responses was not dose-dependent and varied among individuals.

“At dose levels of 10 μg or higher, the magnitude of CD4 + T cell responses was not dose-dependent and varied between individuals.”

May combine two claims.

Neutralizing-antibody GMTs against the two B.1.351-lineage spike pseudoviruses were reduced, but no escape from neutralization occurred.

“Although neutralizing-antibody GMTs against the two pseudoviruses representing B.1.351-lineageS proteins were neutralized at reduced GMTs, no escape from neutralization was noted.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, any local reaction was reported in 42 of 48 participants (88%).

“Any local reaction, n (%) 7 (58) 12 (100) 12 (100) 1 1 (92) 42 (88)”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, a grade 3 or higher systemic reaction was reported in 0% of the 1-μg dose cohort.

“Any grade ≥3 systemic reaction, n (%) 0 (0) 1 ( 8) 2 ( 17) 3 ( 25”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, a grade 3 or higher systemic reaction was reported in 17% of the 20-μg dose cohort.

“Any grade ≥3 systemic reaction, n (%) 0 (0) 1 ( 8) 2 ( 17) 3 ( 25”

Classified as probably not a substantial claim.

Sera were obtained from 38 individuals who had been infected with SARS-CoV-2 or recovered from COVID-19, aged 18-83 years, at least 14 days after PCR-confirmed diagnosis and while asymptomatic.

“Sera from individuals (n = 38) who had been infected with SARS-CoV-2 or recovered from COVID-19 were drawn from donors 18-83 years of age at least 14 days after PCR-confirmed diagnosis and at a time at which the participants were asymptomatic.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

PBMC donors had asymptomatic or mild infections (n=16) or had been hospitalized (n=2).

“PBMC donors had asymptomatic or mild infections (n = 16, clinical score 1 and 2) or had been hospitalized (n = 2, clinical score 4 and 5).”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the second dose, any systemic reaction was reported in 31 of 46 participants (67%).

“Any systemic reaction, n (%) 4 (36) 7 (64) 10 (83) 10 (83) 31 (67)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the first dose, any local reaction was reported in 40 of 48 participants (83%) across all dose cohorts.

“Any local reaction, n (%) 6 (50) 12 (100) 12 (100) 1 0 (83) 40 (83)”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, a grade 3 or higher systemic reaction was reported in 25% of the 30-μg dose cohort.

“Any grade ≥3 systemic reaction, n (%) 0 (0) 1 ( 8) 2 ( 17) 3 ( 25”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, no participant (0 of 48) had a grade 3 or higher local reaction.

“Any grade ≥3 local reaction, n (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the first dose, no participant (0 of 48) had a grade 3 or higher local reaction.

“Any grade ≥3 local reaction, n (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)”

Probably not a substantial claim: may not pass S3 (load-bearing).

One participant in the 1-μg dose cohort had non-treatment-related gastroenteritis on days 6-8.

“One participant in the 1-μg dose cohort (outlier on day 8 in a and highest dataset in b) presented with a non-treatment-related gastroenteritis on days 6-8.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, any systemic reaction was reported in 44 of 48 participants (92%).

“Any systemic reaction, n (%) 9 (75) 12 (100) 1 1 (92) 12 (100) 4 4 (92)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the second dose, any local reaction was reported in 35 of 46 participants (76%).

“Any local reaction, n (%) 4 (36) 10 (91) 10 (83) 11 (92) 35 (76)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the second dose, a grade 3 or higher systemic reaction was reported in 5 of 46 participants (12%).

“Any grade ≥3 systemic reaction, n (%) 0 (0) 1 (9) 1 (8) 3 (25) 5 (12)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the first dose, a grade 3 or higher systemic reaction was reported in 1 of 48 participants (2%).

“Any grade ≥3 systemic reaction, n (%) 0 (0) 0 (0) 1 (8) 0 (0) 1 (2)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the second dose, no participant (0 of 46) had a grade 3 or higher local reaction.

“Any grade ≥3 local reaction, n (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)”

Probably not a substantial claim: may not pass S3 (load-bearing).

After the first dose, any systemic reaction was reported in 39 of 48 participants (81%).

“Any systemic reaction, n (%) 9 (75) 12 (100) 9 (75) 9 (75) 39 (81)”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the combined interval, a grade 3 or higher systemic reaction was reported in 8% of the 10-μg dose cohort.

“Any grade ≥3 systemic reaction, n (%) 0 (0) 1 ( 8) 2 ( 17) 3 ( 25”

Classified as probably not a substantial claim.

PBMC samples were collected from 18 individuals who had been infected with SARS-CoV-2 or recovered from COVID-19, aged 22-79 years, 30-62 days after PCR-confirmed diagnosis and while asymptomatic.

“PBMC samples from individuals (n = 18) who had been infected with SARS-CoV-2 or recovered from COVID-19 were collected from donors 22-79 years of age 30-62 days after PCR-confirmed diagnosis, when donors were asymptomatic.”

May combine two claims.

Observational data show that BNT162b2 reduces laboratory-confirmed infection and viral load in infected individuals.

“The observational data also demonstrate that BNT162b2 reduces laboratory-confirmed infection, as well as viral load in individuals who are infected [3][4][5][6] .”

• cites [3][4][5][6]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

mRNA vaccines are molecularly well-defined and can be synthesized efficiently from DNA templates by in vitro transcription.

“mRNA vaccines are molecularly well-defined and synthesized efficiently from DNA templates by in vitro transcription [8][9][10] .”

• cites [8][9][10]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

BNT162b2 induces an adaptive humoral and poly-specific cellular immune response targeting epitopes conserved across a broad range of variants, at well-tolerated doses.

“In summary, BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at”

• Also stated in: § BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans · plain

  “BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at well-tolerated doses.”

May combine two claims.

This favourable phenotype can respond rapidly to infection but has limited IFNγ production capacity, making it less likely to be detected in functional T cell assays with PBMCs.

“This favourable phenotype has the potential to respond rapidly to infection, but has a limited capacity to produce IFNγ, and thus is less likely to be detected in functional T cell assays with PBMCs.”

May combine two claims.

The clinical study's limitations include small sample size, lack of representation of populations of interest, and limited blood sample availability for deeper T cell analysis.

“The limitations of our clinical study include the small sample size, the lack of representation of populations of interest and limited availability of blood samples for a more in-depth T cell analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The trial was conducted in Germany according to the Declaration of Helsinki and Good Clinical Practice Guidelines, with approval from an independent ethics committee and the competent regulatory authority.

“The trial was carried out in Germany in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines and with approval by an independent ethics committee (Ethik-Kommission of the Landesärztekammer Baden-Württemberg, Stuttgart, Germany) and the competent regulatory authority (Paul-Ehrlich Institute, Langen, Germany).”

Probably not a substantial claim: may not pass S3 (load-bearing).

All participants with available data were included in the immunogenicity analyses.

“All participants with data available were included in the immunogenicity analyses.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The sample size for the reported part of the study was not determined by statistical hypothesis testing.

“The sample size for the reported part of the study was not based on statistical hypothesis testing.”

May combine two claims.

The reporter virus produced plaque morphologies similar to wild-type virus and growth curves indistinguishable from wild-type virus.

“The reporter virus generates similar plaque morphologies and indistinguishable growth curves from wild-type virus.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The experiments were not randomized, and investigators were not blinded to allocation during experiments or outcome assessment.

“The experiments were not randomized, and investigators were not blinded to allocation during experiments and outcome assessment.”

May combine two claims.

BNT162b2 induces a broad immune response comprising SARS-CoV-2 spike-specific neutralizing antibodies and poly-specific CD4+ and CD8+ T cells.

“We show that BNT162b2 induces a broad immune response with SARS-CoV-2 S-specific neutralizing antibodies and poly-specific CD4 + and CD8 + T cells.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Progression within a dose-escalation cohort and dose escalation required review of data by a safety review committee.

“Progression in that cohort and dose escalation required data review by a safety review committee.”

Probably not a substantial claim: may not pass S3 (load-bearing).

All participants gave written informed consent.

“All participants provided written informed consent.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

One participant in the 10-μg dose cohort had concurrent moderate nasopharyngitis unrelated to the study drug when the booster dose was due, did not receive the booster dose, and remained in the study for follow-up.

“Another participant (10-μg dose cohort) presented with concurrent moderate nasopharyngitis unrelated to the study drug when the booster dose was due; this participant did not receive the booster dose but remained on the study for follow-up.”

Probably not a substantial claim: may not pass S3 (load-bearing).

One participant in the 1-μg dose cohort withdrew before the booster dose for reasons unrelated to the study drug and was unavailable for further follow-up.

“One participant (1-μg dose cohort) withdrew before the booster dose for reasons unrelated to the study drug and was not available for further follow-up.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Cell lines were tested for mycoplasma contamination after receipt and before expansion and cryopreservation.

“Cell lines were tested for mycoplasma contamination after receipt and before expansion and cryopreservation.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Sentinel dosing was carried out in every dose-escalation cohort.

“Sentinel dosing was performed in each dose-escalation cohort.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Adverse event grading followed US Food and Drug Administration recommendations.

“Grading of adverse events was performed according to US Food and Drug Administration recommendations 53 .”

• cites [53]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Twelve participants in each dose cohort received both the priming and booster doses, except that two participants missed the booster: one in the 1-μg cohort withdrew for a reason unrelated to the study drug, and one in the 10-μg cohort had concurrent nasopharyngitis not related to the study drug.

“Twelve participants per dose cohort received the priming and the booster doses, except for two participants who did not receive the booster dose owing to a study-drug-unrelated withdrawal by one participant (1-μg dose level), and concurrent nasopharyngitis not related to the study drug in another participant (10-μg dose level).”

Probably not a substantial claim: may not pass S3 (load-bearing).

One pseudovirus variant carried four mutations from the S protein of the B.1.1.298 lineage: Y453F, D614G, I692V, and M1229I.

“One variant had four mutations from S of the B.1.1.298lineage (also referred to as SARS-CoV-2/hu/DK/CL-5/1) (Y453F/D614G/I692V/ M1229I) 28 .”

• cites [28] Lassaunière, R. et al. Working paper on SARS-CoV-2 spike mutations arising in Danish mink, their 2 spread to humans and neutralization data, https://files.ssi.dk/Mink-cluster-5-short-report_AFO2 (2020).Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Probably not a substantial claim: may not pass S3 (load-bearing).

Participant PBMCs were tested without replicates in the flow cytometry analysis.

“Participant PBMCs were tested without replicates.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Each serum was tested in duplicate.

“Each serum was tested in duplicate”

Probably not a substantial claim: may not pass S3 (load-bearing).

Using the geometric mean accounts for the non-normal distribution of antibody concentrations and titers that span several orders of magnitude.

“Using the geometric mean accounts for non-normal distribution of antibody concentrations and titres that span several orders of magnitude.”

Probably not a substantial claim: may not pass S3 (load-bearing).

One participant in the 20-μg dose cohort who had a strong pre-existing CD4+ T cell response to S pool 2 was excluded.

“One participant from the 20-μg dose cohort with a strong pre-existing CD4 + T cell response to S pool 2 was excluded.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Participant PBMCs were tested without replicates in panels b-e.

“Participant PBMCs were tested without replicates (b-e).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

IFNγ ELISpot tests were run in duplicate and included a positive control.

“Tests were performed in duplicate and with a positive control (anti-CD3 monoclonal antibody CD3-2 (1:1,000; Mabtech)).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Spot count data from two participants in the 20-μg dose cohort could not be normalized and were not plotted.

“Spot count data from two participants from the 20-μg dose cohort could not be normalized and are not plotted.”

• Also stated in: § Statistical analysis · plain

  “Spot count data from two participants from the 20-μg dose cohort could not be normalized and are not plotted.”