Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models
Open accessAbstract
Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve control of the COVID-19 pandemic. We compare monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein in a transgenic mouse and a Wistar rat model. The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized female Wistar rats also contain neutralizing antibodies against the B.1.1.529 (Omicron BA.1 and BA.5) variants. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.
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Written from the paper’s full text.
TL;DR
A low-dose, unmodified bivalent mRNA vaccine encoding Beta and Delta SARS-CoV-2 spike proteins protected female K18-hACE2 transgenic mice from Beta- and Delta-induced lethality and reduced viral replication, despite containing half the mRNA dose of each monovalent vaccine. In female Wistar rats, bivalent vaccination also induced neutralizing antibodies against Omicron BA.1 and BA.5, with the Beta component appearing to drive broader neutralization.
Key findings
- In female K18-hACE2 mice, all vaccinated groups were protected from SARS-CoV-2-induced lethality after Beta or Delta challenge, whereas all Beta-challenged and 67% of Delta-challenged sham-vaccinated animals succumbed.
- The bivalent vaccine contained 0.25 µg mRNA of each variant (total 0.5 µg) but induced neutralizing antibody titres comparable to the 0.5 µg monovalent Beta and Delta vaccines; it also induced significantly higher nAb titres than ancestral CV2CoV and significantly higher sVNT inhibition against Omicron BA.1 than the monovalent vaccines.
- The bivalent vaccine significantly reduced viral replication in Beta- and Delta-challenged mice; no SARS-CoV-2 genomic RNA or subgenomic RNA was detected in all but one Beta-challenged, bivalent-vaccinated animal, and Delta replication in conchae was abolished in all vaccinated groups.
- Monovalent and bivalent mRNA vaccines induced lung CD8+ tissue-resident memory T cells, antigen-specific CD4+ and CD8+ responses, and IFNγ/granzyme B production; the bivalent formulation maintained these T cell response qualities at lower antigen doses. Sera from bivalent-vaccinated female Wistar rats neutralized Omicron BA.1 and BA.5, with CV2CoV.351 (Beta) contributing to broader nAb breadth.
Methods
- Female K18-hACE2 transgenic mice (8–10 weeks old) were vaccinated intramuscularly on Day 0 and Day 28 with 0.5 µg CV2CoV, CV2CoV.351, CV2CoV.617.2, bivalent CV2CoV.351 + CV2CoV.617.2 (0.25 µg each), or NaCl, then challenged on Day 56 with 10^4.4 TCID50 Beta or Delta; oral swabs were taken Day 4 and organs Day 10.
- Female Wistar rats (7–8 weeks old) were vaccinated on Day 0 and Day 21 with 8 µg monovalent vaccines or bivalent formulations containing 4 µg of each mRNA; neutralizing antibody titres against Delta and Omicron BA.1/BA.5 were tested at Day 42.
- Analyses included RT-qPCR for viral genomic and subgenomic RNA, RBD ELISA, virus neutralization tests, surrogate virus neutralization tests, flow cytometry for T cell responses, Kaplan–Meier survival analysis, one-way/two-way ANOVA with Dunn’s multiple comparison test, and Spearman correlation.
Limitations
- The paper states that the characteristic drop in vaccine effectiveness in humans with new variants was not observed in the mouse model, highlighting a potential limitation of the model’s predictive power; it also notes that further studies using lower doses are needed to understand optimal dose ranges and compositions.
- The paper states that the role, durability, and specificity of TRM CD8+ T cells in protection require further investigation using antibody-mediated depletion, and that TRM quantification has yielded variable results across studies.
- The text makes evident that only female animals were used, that Omicron was assessed by neutralization rather than challenge, and that the protective efficacy data come from small animal models rather than humans.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
44 of 46 cited sources checked · 22 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Omicron does not induce relevant cross-protective neutralizing antibody titres in SARS-CoV-2 naïve populations.
“Unfortunately, while Omicron appears to cause less severe disease than other variants4, it does not induce relevant cross-protective neutralizing antibody (nAb) titres in SARS-CoV-2 naïve populations, meaning they may be less protected against future infection compared with those previously exposed to other variants or vaccinated5.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [5] Rössler, A. Knabl, L. von Laer, D. & Kimpel, J. Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection. N Engl J Med. 386, 1764–1766 (2022). source
- Findingcitation
0.5 μg was the lowest tested dose of CV2CoV to induce detectable spike-specific IFNγ producing CD8+ cells.
“This dosage was based on previous findings from comparative preclinical evaluations of CVnCoV and the current optimized candidate vaccine CV2CoV13, whereby 0.5 µg was the lowest tested dose to fully protect against lethality and induce abundant neutralizing antibodies (Fig. S1a) and induce detectable spike-specific interferon γ (IFNγ) producing CD8+ cells (Fig. S1b).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [13] Hoffmann, D. et al. CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2. Nat. Commun. 12, 4048 (2021). source
The Results (page unavailable) say CV2CoV was tested at doses from 0.5 to 8 µg, establishing 0.5 µg as the lowest tested dose. They report antibody responses and protection at that dose, but do not report detectable spike-specific IFNγ-producing CD8+ cells; the Discussion mentions earlier CD8+ findings for CVnCoV, not CV2CoV. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
Several SARS-CoV-2 variants of concern, such as Beta and Omicron, evade humoral responses elicited by vaccines based on ancestral S-protein sequences.
“Several VOCs which have mutated, such as Beta1 and Omicron2, evade humoral responses elicited by vaccines based on ancestral S-protein sequences3.”
Quote in the paperSubstantial claim3 of 3 sources checked- cites [1] Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438–443 (2021). source
The Article (p. 5) reports preliminary evidence that 501Y.V2 (Beta) escapes neutralizing antibodies in convalescent plasma. It says assays using vaccine recipients’ plasma were still underway, so it does not establish escape from vaccine-elicited responses; the cited passages also do not address Omicron. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [2] McCallum, M. et al. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement. Science 375, 864–868 (2022). source
- cites [3] Planas, D. et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 602, 671–675 (2022). source
The ‘Sensitivity of Omicron to sera from vaccinees’ section reports that sera collected five months after two Pfizer doses showed almost no detectable neutralization of Omicron, supporting escape from vaccine-elicited antibodies. The paper compares those sera with an ancestral viral strain, but the passages do not establish that the vaccines were based on ancestral spike-protein sequences. Its reported vaccine-serum experiments concern Omicron, not Beta; Beta has a separate citation in the citing sentence. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
The accumulation of memory cells at mucosal sites is critical for the control of viral pneumonia.
“The accumulation of memory cells at mucosal sites is critical for the control of viral pneumonia and their presence has been reported to be associated with less severe COVID-19 symptoms32.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [32] Liao, M. et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med. 26, 842–844 (2020). source
The paper’s T-cell discussion reports that memory T-cell responses are necessary for resolving SARS-CoV infection in mice. Its results also find more expanded CD8+ T cells with tissue-resident features in bronchoalveolar samples from moderate than severe COVID-19 cases. These passages support a role for local T cells, but do not establish that accumulation of memory cells at mucosal sites is critical for controlling viral pneumonia generally. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
The mRNA CV2CoV vaccine does not include chemically modified nucleosides.
“does not include chemically modified nucleosides, as previously described10.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [10] Roth, N. et al. Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homologous and heterologous neutralising antibody responses. Vaccines 10, 1251 (2022). source
- Premisecitation
Rat-derived data translated very well to improved immunogenicity and protective efficacy in a non-human primate challenge model for SARS-CoV-2.
“The rat-derived data translated very well to improved immunogenicity and protective efficacy in a non-human primate challenge model for SARS-CoV-210,11 and our cross-neutralization results emphasize the broad antigen coverage induced by the bivalent vaccine.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [10] Roth, N. et al. Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homologous and heterologous neutralising antibody responses. Vaccines 10, 1251 (2022). source
- cites [11] Gebre, M. S. et al. Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine. Nature 601, 410–414 (2022). source
The Discussion (page not available in our copy) reports greater immune responses and improved protection against SARS-CoV-2 challenge with CV2CoV than with CVnCoV in macaques. The Main section describes earlier protection findings in ACE2-transgenic mice, not rats; our copy does not establish that rat-derived data translated to the primate results. (LLM, conf=0.87)
Experimental — accuracy not yet measured
- Premisecitation
Previous studies did not unveil variability between sexes.
“Previous studies did not unveil variability between sexes10 and manipulation of female animals reduces the biosafety risks in BSL3 during challenge infection.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [10] Roth, N. et al. Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homologous and heterologous neutralising antibody responses. Vaccines 10, 1251 (2022). source
Materials and Methods §2.3 says the study used female and male rats, but does not compare outcomes by sex. Results §3.2 reports no body-weight difference between vaccine groups, not between sexes. Searches for sex differences and male-versus-female antibody responses found no passage establishing the claimed absence of sex variability; page numbers were not available in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
- Findingown data
Sera from bivalent mRNA vaccine immunized female Wistar rats contain neutralizing antibodies against the Omicron BA.1 and BA.5 variants.
“Sera from bivalent mRNA vaccine immunized female Wistar rats also contain neutralizing antibodies against the B.1.1.529 (Omicron BA.1 and BA.5) variants.”
Quote in the paperSubstantial claim - Findingown data
nAb titres induced by the monovalent mRNA vaccines were only statistically significantly higher than CV2CoV when they were assessed using the VOC they were designed against.
“Irrespective of the VOC used for the assessment of nAbs, the bivalent mRNA vaccine induced statistically significantly higher nAb titres compared to those elicited by CV2CoV; whereas nAb titres induced by the monovalent mRNA vaccines were only statistically significantly higher than CV2CoV when they were assessed using the VOC they were designed against (Fig. 2a, b).”
Quote in the paperSubstantial claim - Findingown data
nAb titres were significantly higher for the bivalent vaccine compared with the monovalent vaccines in the sVNT assay against Omicron BA.1.
“In addition, nAbs titres were significantly higher for the bivalent vaccine compared with the monovalent vaccines (Fig. 2c).”
Quote in the paperSubstantial claim - Findingown data
Including the Beta S-protein sequence in the bivalent vaccine appeared to improve the neutralizing capacity of sera against Omicron BA.1 compared with vaccines without Beta S-protein, although statistical significance was not achieved.
“Including the Beta S-protein sequence in the bivalent vaccine appeared to improve the neutralizing capacity of sera against Omicron BA.1, compared with vaccines without Beta S-protein, although statistical significance was not achieved (Fig. 2d).”
Quote in the paperNot a substantial claim - Findingown data
The bivalent mRNA vaccine induces enrichment of lung-resident memory CD8+ T cells.
“The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality.”
Quote in the paperSubstantial claim - Findingown data
2 μg and 8 μg doses of CV2CoV.351 vaccination induced higher nAbs against Omicron BA.1 than CV2CoV.617.
“We observed that 2 µg and 8 µg doses of CV2CoV.351 vaccination induced higher nAbs against Omicron BA.1 than CV2CoV.617, suggesting that the increased capacity of the bivalent vaccine to neutralize Omicron BA.1 was dominated by CV2CoV.351 (Fig. 2e).”
Quote in the paperSubstantial claim - Findingown data
SARS-CoV-2 genomic RNA or subgenomic RNA was not detected in oral swabs collected on Day 4, or in lung, cerebellum and cerebrum samples taken on Day 10, in all but one of the Beta-challenged, bivalent-vaccinated animals.
“We were unable to detect SARS-CoV-2 genomic RNA (Fig. 1c–e and Fig. S3c, d) or subgenomic RNA (sgRNA) (Tables S2 and S3) in oral swabs collected on Day 4, or in lung, cerebellum and cerebrum samples taken on Day 10 in all but one of the Beta-challenged, bivalent-vaccinated animals, indicating that productive infection was prevented.”
Quote in the paperSubstantial claim - Findingown data
Compared with CV2CoV, the monovalent CV2CoV.351 and the bivalent vaccine induced significantly higher nAb titres in a surrogate VNT inhibition assay against Omicron BA.1.
“Compared with CV2CoV, the monovalent CV2CoV.351 and the bivalent vaccine induced significantly higher nAb titres in a surrogate VNT inhibition (sVNT) assay against Omicron BA.1 (Fig. 2c).”
Quote in the paperSubstantial claim - Findingown data
67% of Delta-challenged sham-vaccinated animals succumbed to infection.
“Following challenge with Beta and Delta variants (104.4 TCID50) on Day 56, all vaccinated mice were protected from SARS-CoV-2-induced lethality and virus spread, while all Beta-challenged and 67% of Delta-challenged sham-vaccinated animals succumbed to infection (Fig. 1a, b and Fig. S3a, b).”
Quote in the paperSubstantial claim - Findingown data
All Beta-challenged sham-vaccinated animals succumbed to infection.
“Following challenge with Beta and Delta variants (104.4 TCID50) on Day 56, all vaccinated mice were protected from SARS-CoV-2-induced lethality and virus spread, while all Beta-challenged and 67% of Delta-challenged sham-vaccinated animals succumbed to infection (Fig. 1a, b and Fig. S3a, b).”
Quote in the paperSubstantial claim - Findingown data
The suppression of viral replication in the upper respiratory tract induced by the monovalent vaccines differed depending on the challenge virus.
“The suppression of viral replication in the upper respiratory tract (URT) induced by the monovalent vaccines differed depending on the challenge virus.”
Quote in the paperNot a substantial claim - Findingown data
The bivalent mRNA vaccine protects transgenic female mice from SARS-CoV-2 lethality.
“The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality.”
Quote in the paperSubstantial claim - Findingown data
No significant difference in nAb titres between CV2CoV.351 and CV2CoV.617.2 at 2 μg and 8 μg against Delta was observed.
“No significant difference in nAb titres between CV2CoV.351 and CV2CoV.617.2 at 2 µg and 8 µg against Delta were observed (Fig. S5), and the increased breadth of nAbs with CV2CoV.351 only declined at lower concentrations (Fig. S6).”
Quote in the paperNot a substantial claim - Findingown data
The bivalent mRNA vaccine induced similarly high nAb titres as the Beta and Delta monovalent vaccines with their respective homologous challenges.
“The bivalent mRNA vaccine induced similarly high nAb titres as the Beta and Delta monovalent vaccines with their respective homologous challenges (Fig. 2a, b), despite the bivalent vaccine containing half the mRNA amount of each monovalent vaccine (0.25 µg vs. 0.5 µg).”
Quote in the paperSubstantial claim - Findingown data
The bivalent vaccine reduced viral load in the conchae equivalent to that observed with the matched monovalent vaccine after Beta challenge.
“While the bivalent vaccine reduced viral load in the conchae, equivalent to that observed with the matched monovalent vaccine after Beta challenge (Fig. 1d), replication of the Delta variant in the conchae was abolished (no detectable sgRNA) in all vaccinated groups (Table S3).”
Quote in the paperSubstantial claim - Findingown data
The blended low-dose bivalent mRNA vaccine induces comparable neutralizing antibody titres to the respective monovalent vaccines.
“The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality.”
Quote in the paperSubstantial claim - Findingown data
Replication of the Delta variant in the conchae was abolished in all vaccinated groups.
“While the bivalent vaccine reduced viral load in the conchae, equivalent to that observed with the matched monovalent vaccine after Beta challenge (Fig. 1d), replication of the Delta variant in the conchae was abolished (no detectable sgRNA) in all vaccinated groups (Table S3).”
Quote in the paperSubstantial claim - Findingown data
Both the monovalent and bivalent mRNA vaccines triggered T cell responses dominated by increased numbers and ratios of lung CD45iv- CD8+ T cells.
“We observed that both the monovalent and bivalent mRNA vaccines triggered T cell responses dominated by increased numbers and ratios of lung CD45iv- CD8+ T cells (Fig. 3a and Fig. S8a, b).”
Quote in the paperSubstantial claim - Findingown data
The bivalent mRNA vaccine induces antigen-specific CD4+ and CD8+ responses.
“The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality.”
Quote in the paperSubstantial claim - Findingown data
The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice.
“The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice.”
Quote in the paperSubstantial claim - Findingown data
Irrespective of the VOC used for assessment of nAbs, the bivalent mRNA vaccine induced statistically significantly higher nAb titres compared to those elicited by CV2CoV.
“Irrespective of the VOC used for the assessment of nAbs, the bivalent mRNA vaccine induced statistically significantly higher nAb titres compared to those elicited by CV2CoV; whereas nAb titres induced by the monovalent mRNA vaccines were only statistically significantly higher than CV2CoV when they were assessed using the VOC they were designed against (Fig. 2a, b).”
Quote in the paperSubstantial claim - Findingown data
Sera from Wistar rats vaccinated with CV2CoV or CV2CoV.617.2 monovalent vaccines, or vaccines combining CV2CoV617.2 with either CV2CoV or CV2CoV.351, had high levels of nAb titres against Delta.
“Within additional experiments in a different animal model, serum from Wistar rats vaccinated with CV2CoV or CV2CoV.617.2 mRNA vaccines (monovalent; 8 µg), or vaccines combining CV2CoV617.2 with either CV2CoV or CV2CoV.351 (bivalent; 4 µg of each) on Day 0 and Day 21 (Fig. S4) had high levels of nAb titres against Delta (Fig. 2d).”
Quote in the paperNot a substantial claim - Findingown data
The same pattern of higher nAb titres against Omicron BA.5 was observed in sera from CV2CoV.351 vaccinated animals.
“The same pattern was observed for nAb titres against Omicron BA.5 in sera from CV2CoV.351 vaccinated animals (Fig. 2f).”
Quote in the paperSubstantial claim - Findingown data
The increased breadth of nAbs with CV2CoV.351 only declined at lower concentrations.
“No significant difference in nAb titres between CV2CoV.351 and CV2CoV.617.2 at 2 µg and 8 µg against Delta were observed (Fig. S5), and the increased breadth of nAbs with CV2CoV.351 only declined at lower concentrations (Fig. S6).”
Quote in the paperNot a substantial claim - Findingown data
Following Beta and Delta challenge, all vaccinated mice were protected from SARS-CoV-2-induced lethality and virus spread.
“Following challenge with Beta and Delta variants (104.4 TCID50) on Day 56, all vaccinated mice were protected from SARS-CoV-2-induced lethality and virus spread, while all Beta-challenged and 67% of Delta-challenged sham-vaccinated animals succumbed to infection (Fig. 1a, b and Fig. S3a, b).”
Quote in the paperSubstantial claim - Findingown data
Lower concentrations of unmodified mono- or bivalent mRNA vaccines induced lung parenchymal tissue resident T cells.
“While TRM cells are induced by high concentration mRNA vaccines31; we report that lower concentrations of unmodified mono- or bivalent mRNA vaccines induced lung parenchymal tissue resident T cells.”
Quote in the paperSubstantial claim - Findingown data
The increase in lung CD8+ T cells was accompanied by higher numbers of TRM cells and markers associated with TRM such as CXCR3 and PD-1.
“This increase was accompanied by higher numbers of TRM (CD45iv-CD3+γδTCR-CD8+CD44highCD62L-CD103+CD69+ T cells) and markers associated with TRM such as CXCR3 (for homing) and PD-1 (for regulation of activation of TRM) (Fig. 3c–d and Fig. S8b).”
Quote in the paperSubstantial claim - Findingown data
The frequency of TRM+, CXCR3+ and PD-1+ CD8+ T cells was significantly upregulated in CD45iv- tissue CD8+ T cells compared to CD45iv+ lung vascular CD8+ T cells.
“The frequency of TRM+, CXCR3+ and PD-1+ CD8+ T cells was significantly upregulated in CD45iv- tissue CD8+ T cells compared to CD45iv+ lung vascular CD8+ T cells (Fig. 3e–g).”
Quote in the paperSubstantial claim - Findingnone given
Intramuscular application of unmodified mono- and bivalent mRNA vaccines induced S-peptide specific and TRM CD8+ T cell responses at mucosal sites.
“In addition, intramuscular application of unmodified mono- and bivalent mRNA vaccines induced S-peptide specific and TRM CD8+ T cell responses at mucosal sites.”
Quote in the paperNot a substantial claim - Findingown data
The frequency of CD45iv-CD8+ TRM cells correlated with S-peptide specific GrzB+ lung CD8+ T cells.
“Our analysis did not allow detection of S-peptide specific TRM cells, however, the frequency of CD45iv-CD8+ TRM cells correlated with S-peptide specific GrzB+ lung CD8+ T cells (Fig. 3j).”
Quote in the paperNot a substantial claim - Findingown data
The characteristic drop in vaccine effectiveness in humans with new variants was not observed in the mouse model.
“The characteristic drop in vaccine effectiveness in humans with new variants was not observed in the mouse model, highlighting a potential limitation of the predictive power of the model; however, both models used in our study provide complementary insights regarding the mechanism of action of the bivalent vaccine.”
Quote in the paperSubstantial claim - Findingnone given
The presence of CV2CoV.351 has a favourable impact on the observed nAb breadth.
“In particular, the presence of CV2CoV.351 has a favourable impact on the observed nAb breadth.”
Quote in the paperSubstantial claim - Findingown data
Lung CD8+ T cells from vaccinated animals responded to S-peptide by upregulation of IFNγ and granzyme (GrzB).
“Lung CD8+ T cells from vaccinated animals responded to S-peptide by upregulation of IFNγ and granzyme (GrzB) (Fig. 3h, i).”
Quote in the paperSubstantial claim - Findingown data
The overall increase of CD4+ T cells and CD4+ TRM cells appeared lower than for CD8+ T cells.
“The pattern followed the observations for CD8 + T cells, however the overall increase of CD4+ T cells and CD4+ TRM cells appeared lower than for CD8+ T cells (Fig. S8a–e).”
Quote in the paperNot a substantial claim - Findingown data
A low-dose, bivalent blended, unmodified mRNA vaccine is highly efficacious in pre-clinical mouse and rat models.
“Our study demonstrates that a low-dose, bivalent blended, unmodified mRNA vaccine is highly efficacious in pre-clinical mouse and rat models.”
Quote in the paperSubstantial claim - Interpretationown data
Low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.
“These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.”
Quote in the paperSubstantial claim - Interpretationown data
Productive infection was prevented in the Beta-challenged, bivalent-vaccinated animals.
“We were unable to detect SARS-CoV-2 genomic RNA (Fig. 1c–e and Fig. S3c, d) or subgenomic RNA (sgRNA) (Tables S2 and S3) in oral swabs collected on Day 4, or in lung, cerebellum and cerebrum samples taken on Day 10 in all but one of the Beta-challenged, bivalent-vaccinated animals, indicating that productive infection was prevented.”
Quote in the paperSubstantial claim - Interpretationown data
The presence of CV2CoV.351 in the bivalent formulation appears to be crucial for the observed broader nAb breadth.
“The presence of CV2CoV.351 in the bivalent formulation appears to be crucial for the observed broader nAb breadth.”
Quote in the paperSubstantial claim - Interpretationreasoning
The bivalent formulation, containing half the amount of each mRNA compared with the monovalent vaccines, resulted in broader antigen coverage.
“Thus, the bivalent formulation, containing half the amount of each mRNA compared with the monovalent vaccines, resulted in broader antigen coverage.”
Quote in the paperSubstantial claim - Interpretationown data
The increased capacity of the bivalent vaccine to neutralize Omicron BA.1 was dominated by CV2CoV.351.
“We observed that 2 µg and 8 µg doses of CV2CoV.351 vaccination induced higher nAbs against Omicron BA.1 than CV2CoV.617, suggesting that the increased capacity of the bivalent vaccine to neutralize Omicron BA.1 was dominated by CV2CoV.351 (Fig. 2e).”
Quote in the paperSubstantial claim - Interpretationown data
The blended bivalent vaccine provided protection against viral replication in the upper respiratory tract with half of the dose of each construct found in the monovalent vaccines.
“Thus, although all vaccines induced protection against SARS-CoV-2 lethality, the blended bivalent vaccine provided protection against viral replication in URT with half of the dose of each construct found in the monovalent vaccines.”
Quote in the paperSubstantial claim - Interpretationown data
The CV2CoV.351/CV2CoV.617.2 bivalent vaccine provides similar protection against Beta and Delta as that observed with the corresponding monovalent vaccines.
“We conclude that the CV2CoV.351/CV2CoV.617.2 bivalent vaccine provides similar protection against Beta and Delta as that observed with the corresponding monovalent vaccines.”
Quote in the paperSubstantial claim - Interpretationreasoning
Both models used in the study provide complementary insights regarding the mechanism of action of the bivalent vaccine.
“The characteristic drop in vaccine effectiveness in humans with new variants was not observed in the mouse model, highlighting a potential limitation of the predictive power of the model; however, both models used in our study provide complementary insights regarding the mechanism of action of the bivalent vaccine.”
Quote in the paperSubstantial claim - Interpretationown data
Cross-neutralization results emphasize the broad antigen coverage induced by the bivalent vaccine.
“The rat-derived data translated very well to improved immunogenicity and protective efficacy in a non-human primate challenge model for SARS-CoV-210,11 and our cross-neutralization results emphasize the broad antigen coverage induced by the bivalent vaccine.”
Quote in the paperSubstantial claim - Interpretationown data
The mRNA vaccines used in this study induced lung SARS-CoV-2 specific TRM T cell responses dominated by CD8+ cytotoxic T cells.
“Thus, the mRNA vaccines used in this study induced lung SARS-CoV-2 specific TRM T cell responses dominated by CD8+ cytotoxic T cells.”
Quote in the paperSubstantial claim - Study design and conductown data
The analysis did not allow detection of S-peptide specific TRM cells.
“Our analysis did not allow detection of S-peptide specific TRM cells, however, the frequency of CD45iv-CD8+ TRM cells correlated with S-peptide specific GrzB+ lung CD8+ T cells (Fig. 3j).”
Quote in the paperNot a substantial claim - Interpretationown data
An unmodified, blended bivalent mRNA vaccine is fully protective in transgenic mice.
“Our study demonstrated that an unmodified, blended bivalent mRNA vaccine is fully protective in transgenic mice and, collectively with additional rat studies, we have elucidated the induced humoral and cellular immune responses.”
Quote in the paperSubstantial claim - Interpretationown data
Blending antigens in lower amounts (bivalent vaccine) maintained the quality, i.e., tissue residency and activation patterns, of T cell immune responses triggered by monovalent vaccines.
“Importantly, blending antigens in lower amounts (bivalent vaccine) maintained the quality, i.e., tissue residency and activation patterns of T cell immune responses triggered by monovalent vaccines.”
Quote in the paperSubstantial claim - Interpretationown data
The bivalent vaccine increases the breadth of nAbs against newly emerging VOCs such as the current Omicron variants.
“Furthermore, the bivalent vaccine increases the breadth of nAbs against newly emerging VOCs such as the current Omicron variants.”
Quote in the paperSubstantial claim
- May combine two claims. 14
- Classified as probably not a substantial claim. 20
May combine two claims.
PremisecitationK18-hACE2 transgenic mice have a human ACE2 receptor which is the major cell entry receptor for SARS-CoV-2.
“These transgenic mice have a human ACE2 receptor which is the major cell entry receptor for SARS-CoV-216,17.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [16] Scialo, F. et al. ACE2: the major cell entry receptor for SARS-CoV-2. Lung 198, 867–877 (2020). source
The Introduction states that ACE2 is used by SARS-CoV-2 to enter human cells, supporting the receptor portion of the claim. Our copy does not establish that K18-hACE2 transgenic mice carry human ACE2; searches for that mouse model and for transgenic mice expressing human ACE2 did not find it. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [17] Winkler, E. S. et al. SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nat. Immunol. 21, 1327–1335 (2020). source
Classified as probably not a substantial claim.
PremisecitationNeutralizing antibodies correlate with protection against COVID-19.
“Antibodies are critical for defence against viruses and nAbs have been shown to correlate with protection against COVID-1918,19 to inform immunization schedules20.”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [18] Plotkin, S. A. Correlates of protection induced by vaccination. Clin. Vaccin. Immunol. 17, 1055–1065 (2010). source
- cites [19] Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205–1211 (2021). source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrototypes of multivalent nanoparticle vaccines induce broad reactivity against different sarbecoviruses.
“For example, prototypes of multivalent nanoparticle vaccines have been reported to induce broad reactivity against different sarbecoviruses7.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [7] Walls, A. C. et al. Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines. Cell 184, 5432–5447.e5416 (2021). source
May combine two claims.
Findingcitation0.5 μg was the lowest tested dose of CV2CoV to fully protect against lethality and induce abundant neutralizing antibodies.
“This dosage was based on previous findings from comparative preclinical evaluations of CVnCoV and the current optimized candidate vaccine CV2CoV13, whereby 0.5 µg was the lowest tested dose to fully protect against lethality and induce abundant neutralizing antibodies (Fig. S1a) and induce detectable spike-specific interferon γ (IFNγ) producing CD8+ cells (Fig. S1b).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [13] Hoffmann, D. et al. CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2. Nat. Commun. 12, 4048 (2021). source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationProtection induced by CV2CoV is superior to CVnCoV in a non-human primate SARS-CoV-2 challenge model.
“Protection induced by CV2CoV was reported to be superior to CVnCoV in a non-human primate SARS-CoV-2 challenge model11.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [11] Gebre, M. S. et al. Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine. Nature 601, 410–414 (2022). source
May combine two claims.
Findingown dataLowering the CV2CoV dose to 0.1 μg mRNA reduced levels of neutralizing antibodies and protected only 50% of challenged mice.
“Lowering the CV2CoV dose to 0.1 µg mRNA reduced levels of neutralizing antibodies and protected only 50% of challenged mice (Fig. S1a, c), which is in line with previous studies using modified mRNA for immunization14.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [14] Israelow, B. et al. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Sci. Immunol. 6, eabl4509 (2021). source
Classified as probably not a substantial claim.
PremisecitationmRNA vaccines induce robust protection against SARS-CoV-2.
“mRNA vaccines are promising candidates for future vaccine approaches, based on their demonstrated ability to induce robust protection against SARS-CoV-28.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [8] Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 596, 109–113 (2021). source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCV2CoV induces high neutralizing antibodies in rats and non-human primates, with titers comparable to those seen with Comirnaty.
“CV2CoV has now entered clinical testing (NCT05260437) and has been shown to induce high neutralizing antibodies in rats10 and non-human primates11, with titers comparable to those seen with Comirnaty, a licensed mRNA COVID-19 vaccine.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [10] Roth, N. et al. Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homologous and heterologous neutralising antibody responses. Vaccines 10, 1251 (2022). source
Results §3.3 reports high neutralising-antibody titres in CV2CoV-vaccinated rats. The Discussion §4 mentions non-human-primate findings from a prior study, but this paper does not report a comparison of CV2CoV titres with Comirnaty; its direct comparator is CVnCoV. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [11] Gebre, M. S. et al. Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine. Nature 601, 410–414 (2022). source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improve homologous and heterologous neutralising antibody responses in rats and non-human primates, compared with CVnCoV and other modified mRNA vaccines.
“The optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV have previously been shown to improve homologous and heterologous neutralising antibody responses in rats and non-human primates, compared with CVnCoV and other modified mRNA vaccines10,11.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [10] Roth, N. et al. Optimised non-coding regions of mRNA SARS-CoV-2 vaccine CV2CoV improves homologous and heterologous neutralising antibody responses. Vaccines 10, 1251 (2022). source
The Abstract and Discussion (page numbers unavailable) report stronger homologous and variant cross-neutralising responses with CV2CoV than with CVnCoV in rats. The Discussion also reports consistent findings from a non-human-primate study. This paper does not establish that CV2CoV outperformed other modified mRNA vaccines. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [11] Gebre, M. S. et al. Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine. Nature 601, 410–414 (2022). source
The Vaccine immunogenicity section (page not available) reports higher neutralising antibody titres against the ancestral strain and several variants with CV2CoV than with CVnCoV in macaques. This paper does not report rat results, and it describes CV2CoV responses as comparable—not superior—to those induced by the modified mRNA vaccine BNT162b2. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTRM cells are induced by high concentration mRNA vaccines.
“While TRM cells are induced by high concentration mRNA vaccines31; we report that lower concentrations of unmodified mono- or bivalent mRNA vaccines induced lung parenchymal tissue resident T cells.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [31] Ying, B. et al. Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains. Sci. Transl. Med. 14, eabm3302 (2022). source
The Results section on immunogenicity in K18-hACE2 mice reports CD8+ and CD4+ T-cell responses in the spleen after a 5 μg mRNA vaccine dose. The Methods section describes testing splenocytes, not tissue-resident memory (TRM) cells. Searches for TRM cells and lung-resident T cells found no passage establishing that high-dose vaccination induced them. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe presence of memory cells at mucosal sites is associated with less severe COVID-19 symptoms.
“The accumulation of memory cells at mucosal sites is critical for the control of viral pneumonia and their presence has been reported to be associated with less severe COVID-19 symptoms32.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [32] Liao, M. et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med. 26, 842–844 (2020). source
In the main text (page unavailable), the paper reports more highly expanded CD8+ T cells with tissue-resident features in bronchoalveolar lavage fluid from moderate than from severe/critical COVID-19 cases. This supports an association between a local T-cell phenotype and disease severity, but the paper describes these cells as effectors with tissue-resident features, not as confirmed memory cells, and compares severity categories rather than symptom levels. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationQuantification of TRM cells has yielded variable results using different modified mRNA vaccine constructs in a mouse model, ranging from detection in the lungs to absence in the same tissue despite using much higher doses of 2-5 μg.
“Quantification of TRM cells has yielded variable results, as reported by others, using different modified mRNA vaccine constructs in a mouse model, ranging from their detection in the lungs14 to absence in the same tissue15 despite using it at much higher doses of 2–5 µg.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [14] Israelow, B. et al. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Sci. Immunol. 6, eabl4509 (2021). source
The Main Text reports that vaccinated mice did not develop high levels of lung-resident memory T cells, supporting the absence attributed to this source. But it specifies a 1 µg Pfizer-BioNTech mRNA vaccine dose, not the claimed 2–5 µg; the separate citation for detection in lungs is outside this verdict. (LLM, conf=0.90)
Experimental — accuracy not yet measured - cites [15] Li, C. et al. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine. Nat. Immunol. 23, 543–555 (2022). source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMultivalent influenza and cytomegalovirus mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines.
“Multivalent influenza21 and cytomegalovirus22 mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines18,23.”
Quote in the paperNot a substantial claim3 of 4 sources checked- cites [21] Chivukula, S. et al. Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza. NPJ Vaccines 6, 1–15 (2021). source
- cites [22] John, S. et al. Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. Vaccine 36, 1689–1699 (2018). source
- cites [18] Plotkin, S. A. Correlates of protection induced by vaccination. Clin. Vaccin. Immunol. 17, 1055–1065 (2010). source
- cites [23] Kent, S. J. et al. Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast? Nat. Rev. Immunol. 22, 387–397 (2022). source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInterest in vaccine-elicited T cell responses has increased due to immune escape by variants, such as Omicron.
“Interest in vaccine-elicited T cell responses has increased due to immune escape by variants, such as Omicron29.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [29] Tarke, A. et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell 185, 847–859.e811 (2022). source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationViral-vector and mRNA vaccines elicit long-lasting S-specific or nucleoprotein-specific CD4+ and CD8+ T cell responses, with broad cross-reactivity against VOCs.
“In addition to humoral responses, cellular immunity contributes to protection against COVID-19 and recent evidence suggests that viral-vector and mRNA vaccines elicit long-lasting S-specific or nucleoprotein-specific CD4+ and CD8+ T cell responses, with broad cross-reactivity against VOCs29,30.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [29] Tarke, A. et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell 185, 847–859.e811 (2022). source
The Results section reports spike-specific CD4+ and CD8+ T-cell responses after mRNA and adenoviral-vector vaccination that largely cross-recognized variants. It also documents memory responses about six months after vaccination, but that later cohort received mRNA vaccines. The paper does not show vaccine-elicited nucleoprotein-specific responses or establish similarly lasting responses for the viral-vector vaccine. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [30] Hajnik, R. L. et al. Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models. Sci. Transl. Med. 14, eabq1945 (2022). source
The Results report that combined mRNA-S+N vaccination elicited S- and N-specific CD4+ and CD8+ T-cell responses in mice at week 5. The Discussion reports cross-recognition of Omicron by S-specific T cells after infection or vaccination, but does not establish broad cross-reactivity of the vaccine-induced responses; it explicitly says their durability remains to be assessed. The paper also does not demonstrate long-lasting T-cell responses from viral-vector vaccines. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCD8+ T cells contribute to virological control of SARS-CoV-2 infection when antibody titres are sub-optimal in non-human primates.
“CD8+ T cells have been shown to contribute to virological control of SARS-CoV-2 infection when antibodies titres were sub-optimal in non-human primates33,34.”
Quote in the paperNot a substantial claim2 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationModified bivalent mRNA SARS-CoV-2 vaccines elicited significantly higher nAb responses against recent SARS-CoV-2 variants and non-inferior titres against ancestral virus compared with monovalent vaccines in humans and preclinical animal models.
“In addition, modified bivalent mRNA SARS-CoV-2 vaccines elicited significantly higher nAb responses against recent SARS-CoV-2 variants and non-inferior titres against ancestral virus compared with monovalent vaccines in humans and preclinical animal models9,24.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [9] Scheaffer, S. M. et al. Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant. Nat. Med. https://doi.org/10.1038/s41591-022-02092-8 (2022). source
The Results sections on preclinical vaccination and boosting report stronger neutralization of Omicron variants by bivalent vaccines than by ancestral monovalent mRNA-1273 in mice. The study did not test humans; the Discussion only says its findings are consistent with human serum data from other studies. It also does not establish non-inferiority of ancestral-virus titres, and notes that some variant comparisons did not reach statistical significance. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [24] Chalkias, S. et al. A bivalent Omicron-containing booster vaccine against Covid-19. N. Engl. J. Med. 387, 1279–1291 (2022). source
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
Classified as probably not a substantial claim.
PremisecitationNeutralizing antibodies are one of the key parameters correlating with the observed protective efficacy of the first-generation SARS-CoV-2 mRNA vaccine CVnCoV and a licensed COVID-19 mRNA vaccine.
“Neutralizing antibodies in the sera of the participants will be assessed since they have been identified as one of the key parameters correlating with the observed protective efficacy of the first generation SARS-CoV-2 mRNA vaccine CVnCoV27, and a licensed COVID-19 mRNA vaccine28.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [27] Cromer, D. et al. Relating in vitro neutralization level and protection in the CVnCoV (CUREVAC) trial. Clin. Infect. Dis. 75, e878–e879 (2022). source
- cites [28] Gilbert, P. B. et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science 375, 43–50 (2022). source
May combine two claims.
PremisecitationDepletion of CD8+ T cells following immunization with mRNA vaccine, prior to SARS-CoV-2 challenge, led to different outcomes in a transgenic mouse model, possibly due to the vaccine dose used and variability in nAb concentrations.
“Depletion of CD8+ T cells following immunization with mRNA vaccine, prior to SARS-CoV-2 challenge, led to different outcomes in a transgenic mouse model, possibly due to the vaccine dose used and variability in nAb concentrations14,35.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [14] Israelow, B. et al. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Sci. Immunol. 6, eabl4509 (2021). source
The Main Text (Fig. 4 discussion; page unavailable) describes CD8+ T-cell depletion before SARS-CoV-2 challenge in mRNA-vaccinated K18-hACE2 transgenic mice. It reports similar disease protection and viral RNA levels in depleted and control mice, not a different outcome caused by depletion. The paper specifies a 1 µg vaccine dose but does not attribute differing outcomes to dose or variability in neutralizing-antibody concentrations. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [35] de Alwis, R. et al. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Mol. Ther. 29, 1970–1983 (2021). source
The Results section (page unavailable) reports that CD8+ T-cell depletion before SARS-CoV-2 challenge caused breakthrough infection in vaccinated hACE2 transgenic mice, and specifies a reduced 1 μg vaccine dose. The paper does not attribute differing outcomes between studies to vaccine dose or variability in neutralizing-antibody concentrations; that proposed explanation is not supported by this source. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRepeated immunization extends neutralization to non-homologous variants, possibly through affinity maturation of memory B cell populations.
“Recent studies have revealed that repeated immunization extends neutralization to non-homologous variants, possibly through affinity maturation of memory B cell populations12,25.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [12] Dejnirattisai, W. et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell 185, 467–484.e415 (2022). source
The Results section, “Increased neutralization of Omicron by third-dose booster vaccination” (page unavailable), reports higher Omicron-neutralization titers after a third vaccine dose, supporting the claim that repeated immunization improves neutralization of a non-homologous variant. The paper does not attribute that improvement to affinity maturation of memory B cells; that proposed mechanism is unsupported by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [25] Gruell, H. et al. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat. Med. 28, 477–480 (2022). source
The Main section reports that a BNT162b2 booster substantially increased serum neutralization against Omicron and speculates that ongoing affinity maturation may explain the response. It does not identify memory B cell populations as the mechanism or establish the effect across multiple non-homologous variants; the measured booster response here is to Omicron. No page number is provided in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCellular immunity contributes to protection against COVID-19.
“In addition to humoral responses, cellular immunity contributes to protection against COVID-19 and recent evidence suggests that viral-vector and mRNA vaccines elicit long-lasting S-specific or nucleoprotein-specific CD4+ and CD8+ T cell responses, with broad cross-reactivity against VOCs29,30.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [29] Tarke, A. et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell 185, 847–859.e811 (2022). source
The Introduction (page unavailable) says several lines of evidence point to potential roles for T cells in reducing COVID-19 severity and contributing to protection. That supports the direction of the claim, but the citing sentence states the contribution as established, whereas the source qualifies it as potential. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [30] Hajnik, R. L. et al. Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models. Sci. Transl. Med. 14, eabq1945 (2022). source
May combine two claims.
Findingown dataAnti-RBD total immunoglobulin levels were high in all vaccinated mice, with no notable differences between groups.
“In our study, anti-RBD total immunoglobulin levels were high in all vaccinated mice, with no notable differences between groups (Fig. S3e, f).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataS-peptide specific IFNy+ CD4+ T cells were detectable, but did not correlate with the frequency of CD4+ TRM cells.
“S-peptide specific IFNy+ CD4+ T cells were detectable, but did not correlate with the frequency of CD4+ TRM cells (Fig. S8f, g).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe limit of detection of the RT-qPCR assay was 1 genome copy/μl RNA.
“The limit of detection was calculated to be 1 genome copy/µl RNA.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningDose-sparing, multivalent vaccines combining mRNA encoding the S-protein from variants with unrelated lineages may induce heterologous protection and increase the breadth of immune responses.
“Results suggest that dose-sparing, multivalent vaccines, combining mRNA encoding the S-protein from variants with unrelated lineages may induce heterologous protection and thus increase the breadth of immune responses.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable). May combine two claims.
InterpretationreasoningPreservation of the epitope repertoire may be critical for defence against current and future variants and may bring substantial benefits by contributing to protection against severe disease.
“Preservation of the epitope repertoire may be critical for defence against current and future variants and may bring substantial benefits by contributing to protection against severe disease.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.
Interpretationnone givenGiven their exceptional flexibility for antigen formulation, mRNA vaccine platforms offer advantages regarding adaptability to circulating and emerging variants, and opportunities for designing pan-sarbecovirus vaccines.
“Given their exceptional flexibility for antigen formulation, mRNA vaccine platforms offer advantages regarding adaptability to circulating and emerging variants, and opportunities for designing pan-sarbecovirus vaccines.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataBlending mRNA coding for the spike protein of different variants, including the Beta spike protein, elicited antibodies with substantial breadth and the potential to neutralize newly emerging variants such as BA.5.
“In line with these findings, our study demonstrated that blending mRNA coding for the spike protein of different variants, including the Beta spike protein, elicited antibodies with substantial breadth and the potential to neutralize newly emerging variants such as BA.5.”
Quote in the paperSubstantial claim
The paper relies on this without support.
New escape variants of SARS-CoV-2 will emerge in the future.
“The evolution of further VOCs is unpredictable; however, it is likely that new escape variants will emerge.”
Cites
Khoury, D. S., Cromer, D., Reynaldi, A., Schlub, T. E., Wheatley, A. K., Juno, J. A., Subbarao, K., Kent, S. J., Triccas, J. A., & Davenport, M. P. (2021) · Nature Medicine · doi:10.1038/s41591-021-01377-8 · Cited by 3,742 · see citing works
Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., Cheng, L., Li, J., Wang, X., Wang, F., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0901-9 · Cited by 2,614 · see citing works
Detection of a SARS-CoV-2 variant of concern in South Africa
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., et al. (2021) · Nature · doi:10.1038/s41586-021-03402-9 · Cited by 2,510 · see citing works
Correlates of protection induced by vaccination
Plotkin, S. A. (2010) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00131-10 · Cited by 1,745 · see citing works
Considerable escape of SARS-CoV-2 Omicron to antibody neutralization
Planas, D., Saunders, N., Maes, P., Guivel-Benhassine, F., Planchais, C., Buchrieser, J., Bolland, W.-H., Porrot, F., Staropoli, I., Lemoine, F., et al. (2022) · Nature · doi:10.1038/s41586-021-04389-z · Cited by 1,514 · see citing works
Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
Gilbert, P. B., Montefiori, D. C., McDermott, A. B., Fong, Y., Benkeser, D., Deng, W., Zhou, H., Houchens, C. R., Martins, K., Jayashankar, L., et al. (2022) · Science · doi:10.1126/science.abm3425 · Cited by 1,137 · see citing works
Correlates of Protection Against SARS-CoV-2 in Rhesus Macaques
McMahan, K., Yu, J., Mercado, N. B., Loos, C., Tostanoski, L. H., Chandrashekar, A., Liu, J., Peter, L., Atyeo, C., Zhu, A., et al. (2021) · Nature · doi:10.1038/s41586-020-03041-6 · Cited by 1,068 · see citing works
Wolter, N., Jassat, W., Walaza, S., Welch, R., Moultrie, H., Groome, M., Amoako, D. G., Everatt, J., Bhiman, J. N., Scheepers, C., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00017-4 · Cited by 1,041 · see citing works
SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
Dejnirattisai, W., Huo, J., Zhou, D., Zahradník, J., Supasa, P., Liu, C., Duyvesteyn, H. M. E., Ginn, H. M., Mentzer, A. J., Tuekprakhon, A., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.046 · Cited by 930 · see citing works
Winkler, E. S., Bailey, A. L., Kafai, N. M., Nair, S., McCune, B. T., Yu, J., Fox, J. M., Chen, R. E., Earnest, J. T., Keeler, S. P., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0778-2 · Cited by 901 · see citing works
Tarke, A., Coelho, C. H., Zhang, Z., Dan, J. M., Yu, E. D., Methot, N., Bloom, N. I., Goodwin, B., Phillips, E., Mallal, S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.015 · Cited by 858 · see citing works
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses
Turner, J. S., O’Halloran, J. A., Kalaidina, E., Kim, W., Schmitz, A. J., Zhou, J. Q., Lei, T., Thapa, M., Chen, R. E., Case, J. B., et al. (2021) · Nature · doi:10.1038/s41586-021-03738-2 · Cited by 831 · see citing works
Homologous and Heterologous Covid-19 Booster Vaccinations
Atmar, R. L., Lyke, K. E., Deming, M. E., Jackson, L. A., Branche, A. R., Sahly, H. M. E., Rostad, C. A., Martin, J. M., Johnston, C., Rupp, R. E., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2116414 · Cited by 629 · see citing works
A Bivalent Omicron-Containing Booster Vaccine against Covid-19
Chalkias, S., Harper, C., Vrbicky, K., Walsh, S. R., Essink, B., Brosz, A., McGhee, N., Tomassini, J. E., Chen, X., Chang, Y., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2208343 · Cited by 627 · see citing works
Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement
McCallum, M., Czudnochowski, N., Rosen, L. E., Zepeda, S. K., Bowen, J. E., Walls, A. C., Hauser, K., Joshi, A., Stewart, C., Dillen, J. R., et al. (2022) · Science · doi:10.1126/science.abn8652 · Cited by 535 · see citing works
Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine
Li, C., Lee, A., Grigoryan, L., Arunachalam, P. S., Scott, M. K. D., Trisal, M., Wimmers, F., Sanyal, M., Weidenbacher, P. A., Feng, Y., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01163-9 · Cited by 505 · see citing works
ACE2: The Major Cell Entry Receptor for SARS-CoV-2
Scialo, F., Daniele, A., Amato, F., Pastore, L., Matera, M. G., Cazzola, M., Castaldo, G., & Bianco, A. (2020) · Lung · doi:10.1007/s00408-020-00408-4 · Cited by 481 · see citing works
Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and Monoclonal Antibodies
Wilhelm, A., Widera, M., Grikscheit, K., Toptan, T., Schenk, B., Pallas, C., Metzler, M., Kohmer, N., Hoehl, S., Helfritz, F. A., et al. (2021) · doi:10.1101/2021.12.07.21267432 · Cited by 440 · see citing works
Self-citationGruell, H., Vanshylla, K., Tober-Lau, P., Hillus, D., Schommers, P., Lehmann, C., Kurth, F., Sander, L. E., & Klein, F. (2022) · Nature Medicine · doi:10.1038/s41591-021-01676-0 · Cited by 410 · see citing works
John, S., Yuzhakov, O., Woods, A., Deterling, J., Hassett, K., Shaw, C. A., & Ciaramella, G. (2018) · Vaccine · doi:10.1016/j.vaccine.2018.01.029 · Cited by 229 · see citing works
de Alwis, R., Gan, E. S., Chen, S., Leong, Y. S., Tan, H. C., Zhang, S. L., Yau, C., Low, J. G. H., Kalimuddin, S., Matsuda, D., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.04.001 · Cited by 191 · see citing works
Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Israelow, B., Mao, T., Klein, J., Song, E., Menasche, B., Omer, S. B., & Iwasaki, A. (2021) · Science Immunology · doi:10.1126/sciimmunol.abl4509 · Cited by 189 · see citing works
Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Israelow, B., Mao, T., Klein, J., Song, E., Menasche, B., Omer, S. B., & Iwasaki, A. (2021) · doi:10.1101/2021.05.19.444825 · Cited by 189 · see citing works
Walls, A. C., Miranda, M. C., Schäfer, A., Pham, M. N., Greaney, A., Arunachalam, P. S., Navarro, M.-J., Tortorici, M. A., Rogers, K., O’Connor, M. A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.015 · Cited by 185 · see citing works
Scheaffer, S. M., Lee, D., Whitener, B., Ying, B., Wu, K., Liang, C.-Y., Jani, H., Martin, P., Amato, N. J., Avena, L. E., et al. (2023) · Nature Medicine · doi:10.1038/s41591-022-02092-8 · Cited by 169 · see citing works
Kent, S. J., Khoury, D. S., Reynaldi, A., Juno, J. A., Wheatley, A. K., Stadler, E., John Wherry, E., Triccas, J., Sasson, S. C., Cromer, D., et al. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00716-1 · Cited by 139 · see citing works
CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques
Liu, J., Yu, J., McMahan, K., Jacob-Dolan, C., He, X., Giffin, V., Wu, C., Sciacca, M., Powers, O., Nampanya, F., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abq7647 · Cited by 132 · see citing works
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2022) · Nature · doi:10.1038/s41586-021-04231-6 · Cited by 127 · see citing works
Self-citationHajnik, R. L., Plante, J. A., Liang, Y., Alameh, M.-G., Tang, J., Bonam, S. R., Zhong, C., Adam, A., Scharton, D., Rafael, G. H., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abq1945 · Cited by 122 · see citing works
Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Chivukula, S., Plitnik, T., Tibbitts, T., Karve, S., Dias, A., Zhang, D., Goldman, R., Gopani, H., Khanmohammed, A., Sarode, A., et al. (2021) · npj Vaccines · doi:10.1038/s41541-021-00420-6 · Cited by 117 · see citing works
Kapłonek, P., Fischinger, S., Cizmeci, D., Bartsch, Y. C., Kang, J., Burke, J. S., Shin, S. A., Dayal, D., Martin, P., Mann, C. J., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.01.001 · Cited by 111 · see citing works
Neutralization Profile after Recovery from SARS-CoV-2 Omicron Infection
Rössler, A., Knabl, L., von Laer, D., & Kimpel, J. (2022) · New England Journal of Medicine · doi:10.1056/nejmc2201607 · Cited by 95 · see citing works
Multi‐species ELISA for the detection of antibodies against SARS‐CoV‐2 in animals
Wernike, K., Aebischer, A., Michelitsch, A., Hoffmann, D., Freuling, C. M., Balkema‐Buschmann, A., Graaf, A., Müller, T., Osterrieder, N., Rissmann, M., et al. (2020) · Transboundary and Emerging Diseases · doi:10.1111/tbed.13926 · Cited by 89 · see citing works
Self-citationProtective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
Ying, B., Whitener, B., VanBlargan, L. A., Hassan, A. O., Shrihari, S., Liang, C.-Y., Karl, C. E., Mackin, S., Chen, R. E., Kafai, N. M., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abm3302 · Cited by 85 · see citing works
The Future of SARS-CoV-2 Vaccination — Lessons from Influenza
Monto, A. S. (2021) · New England Journal of Medicine · doi:10.1056/nejmp2113403 · Cited by 51 · see citing works
CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2
Hoffmann, D., Corleis, B., Rauch, S., Roth, N., Mühe, J., Halwe, N. J., Ulrich, L., Fricke, C., Schön, J., Kraft, A., et al. (2021) · doi:10.1101/2021.03.22.435960 · Cited by 48 · cited 2× · see citing works
“Samples (mouse swabs/organs) that tested positive for viral genomic RNA were evaluated using an assay specifically detecting sgRNA of the ORF7a as previously described by Hoffmann et al.(13).”
MethodSelf-citationRelating In Vitro Neutralization Level and Protection in the CVnCoV (CUREVAC) Trial
Cromer, D., Reynaldi, A., Steain, M., Triccas, J. A., Davenport, M. P., & Khoury, D. S. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciac075 · Cited by 23 · see citing works
Roth, N., Schön, J., Hoffmann, D., Thran, M., Thess, A., Mueller, S. O., Petsch, B., & Rauch, S. (2022) · Vaccines · doi:10.3390/vaccines10081251 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
9 of the 47 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Frameworks for transformational breakthroughs in RNA-based medicines
Androsavich, J. R. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00943-2 · Cited by 93 · see citing works
Ying, B., Darling, T. L., Desai, P., Liang, C.-Y., Dmitriev, I. P., Soudani, N., Bricker, T. L., Kashentseva, E. A., Harastani, H., Raju, S., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01743-x · Cited by 49 · see citing works
Huang, L., Zhao, F., He, M., Fang, Y., Ma, X., Lu, S., Li, E., Xiao, H. Q., Zhu, H., Wang, X., et al. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.01.002 · Cited by 23 · see citing works
Animal models for COVID-19 and tuberculosis
Corleis, B., Bastian, M., Hoffmann, D., Beer, M., & Dorhoi, A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1223260 · Cited by 19 · see citing works
Self-citationYing, B., Darling, T. L., Desai, P., Liang, C.-Y., Dmitriev, I. P., Soudani, N., Bricker, T. L., Kashentseva, E. A., Harastani, H., Schmidt, A. G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.04.539332 · Cited by 13 · see citing works
Singh, O. N., Berry, U., Joshi, G., Asuru, T. R., Chandrasekar, K., Narayanan, S., Srivastava, P., Tiwari, M., Chattopadhyay, S., Mehdi, F., et al. (2025) · iScience · doi:10.1016/j.isci.2025.113498 · Cited by 12 · see citing works
“15,28,29 Despite the development of several vaccines against SARS-CoV-2, there is limited access to vaccines globally and there is scope for improving the efficacy and duration of protection offered by the vaccines.”
Multivalent mRNA Vaccine Elicits Broad Protection against SARS-CoV-2 Variants of Concern
Kumari, M., Liang, K.-H., Su, S.-C., et al. (2024) · Vaccines · doi:10.3390/vaccines12070714 · Cited by 9 · see citing works
“Moreover, Corleis et al. recently demonstrated that multivalent mRNA vaccines can confer broad protection against Omicron sublineages at relatively low doses [9].”
BackgroundBivalent mRNA vaccine effectiveness against SARS-CoV-2 variants of concern
Kumari, M., Su, S.-C., Liang, K.-H., Lin, H.-T., Lu, Y.-F., Chen, K.-C., Wy, C., & Wu, H. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00936-0 · Cited by 9 · see citing works
“However, it is important to note that repeated boosting with vaccines against homologous variants may not be effective at preserving the epitope repertoire [30].”
BackgroundHannawi, S., Wu, X., Villalobos, R. E., Burhan, E., Borra, M. D. L., Gupta, R. K., Aquitania, G. P., Ang, B. W., Zabat, G. M. A., Roa, C. C., et al. (2024) · Med · doi:10.1016/j.medj.2024.06.013 · Cited by 8 · see citing works
Roier, S., Adamo, R., Rosini, R., Pezzicoli, A., Scarselli, M., Petsch, B., Jasny, E., & Rauch, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1668937 · Cited by 8 · see citing works
Self-citationAbdoli, A., Jamshidi, H., Taqavian, M., Baghal, M. L., & Jalili, H. (2024) · Scientific Reports · doi:10.1038/s41598-023-50822-w · Cited by 6 · see citing works
“The studies indicate that boosting with bivalent vaccines are feasible approach for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants 28,29 .”
BackgroundClever, S., Limpinsel, L., zu Natrup, C. M., Schünemann, L.-M., Beythien, G., Rosiak, M., Hülskötter, K., Gregor, K. M., Tuchel, T., Kalodimou, G., et al. (2024) · Viruses · doi:10.3390/v16030417 · Cited by 5 · see citing works
SARS‐CoV‐2 variants of concern elicit divergent early immune responses in hACE2 transgenic mice
Fricke, C., Pfaff, F., Ulrich, L., Halwe, N. J., Schön, J., Timm, L., Hoffmann, W., Rauch, S., Petsch, B., Hoffmann, D., et al. (2023) · European Journal of Immunology · doi:10.1002/eji.202250332 · Cited by 3 · see citing works
“Cells were isolated and stained following previously published protocols [88].”
MethodSelf-citationThe discovery and development of mRNA vaccines for the prevention of SARS-CoV-2 infection
Xue, V. W., Wong, S. C. C., Li, B., & Cho, W. C. S. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2218083 · Cited by 2 · see citing works
“But, the bivalent SARS-CoV-2 mRNA vaccines show an increased breadth of neutralization for preventing partial rather than all variants [72,73].”
BackgroundDu, P. F., Li, N., Tang, S., Zhou, Z., Liu, Z., Wang, T., Li, J., Zeng, S., & Chen, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34492 · Cited by 2 · see citing works
“P. Du et al. variants, while the Omicron booster significantly enhanced neutralizing activity against all variants [43].”
BackgroundResultHurst, J. R., Naghibosadat, M., Budowski, P., Li, J., Samaan, P., Budiman, F., Kurtesi, A., Qi, F., Menon, H., Krishnan, R. G., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0314061 · Cited by 1 · see citing works
Kochmann, J., Britzke, T., Halwe, N. J., et al. (2026) · European Journal of Immunology · doi:10.1002/eji.70196 · Cited by 1 · see citing works
“Cells were harvested from lungs as described in [ 48 ] and stained with Cell Trace Far Red (Thermo Fisher), prediluted 1:1000 in prewarmed PBS, for 20 min at 37 ◦ C.”
Self-citationmRNA vaccine-induced IgG mediates nasal SARS-CoV-2 clearance in mice
Fricke, C., Ulrich, L., Kochmann, J., Gergen, J., Kovacikova, K., Roth, N., Beer, J., Schnepf, D., Mettenleiter, T. C., Rauch, S., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102360 · Cited by 1 · see citing works
Self-citationHannawi, S., Villalobos, R. E., Burhan, E., Borra, M. D. L., Gupta, R. K., Aquitania, G. P., Ang, B. W., Zabat, G. M. A., Camilo C. Roa, Jr., Jesus, L. Z. D., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4689124
Additional file 2 of Bivalent mRNA vaccine effectiveness against SARS-CoV-2 variants of concern
Kumari, M., Su, S.-C., Liang, K.-H., Lin, H.-T., Lu, Y.-F., Chen, K.-C., Chen, W.-Y., & Wu, H.-C. (2024) · Figshare · doi:10.6084/m9.figshare.26600476
Additional file 1 of Bivalent mRNA vaccine effectiveness against SARS-CoV-2 variants of concern
Kumari, M., Su, S.-C., Liang, K.-H., Lin, H.-T., Lu, Y.-F., Chen, K.-C., Chen, W.-Y., & Wu, H.-C. (2024) · Figshare · doi:10.6084/m9.figshare.26600470
Guan, X., Cho, H., Qian, S., Liu, Q., & Du, L. (2026) · Vaccines · doi:10.3390/vaccines14010078
- Authors
- Corleis, B., Hoffmann, D., Rauch, S., Fricke, C., Roth, N., Gergen, J., Kovacikova, K., Schlottau, K., Halwe, N. J., Ulrich, L., Schön, J., Wernike, K., Widera, M., Ciesek, S., Mueller, S. O., Mettenleiter, T. C., Maione, D., Petsch, B., Beer, M., & Dorhoi, A.
- Affiliations
- Friedrich-Loeffler-Institut (DE)
- CureVac (Germany) (DE)
- Goethe University Frankfurt (DE)
- GlaxoSmithKline (Italy) (IT)
- Corresponding author
- Beer, Martin
- Dorhoi, Anca
- ORCID
- Venue
- Nature Communications
- Published
- 2023-02-13
- Volume
- 14
- Issue
- 1
- Pages
- 816-816
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9924835
- OpenAlex
- W4320483863
- Cited by
- 22
- References
- 47
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 13 · 2023: 5
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- OpenAgrar (submittedVersion, cc-by)
- Funders
- Bundesministerium für Bildung und Forschung (01KI20703, SARS-CoV-2)
- Bundesministerium für Ernährung und Landwirtschaft
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- bivalent mRNA vaccine, SARS-CoV-2 variants, spike protein, Beta variant, Delta variant, neutralizing antibodies, CD8+ T cells, CD4+ T cells, viral replication, transgenic mouse model, Wistar rat model, multivalent vaccine, COVID-19 vaccine coverage
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Animals, Antibodies, Viral, Female, Mice, Transgenic, Rats, Wistar, Vaccines, Combined, CD8-Positive T-Lymphocytes, Models, Animal, Mice, Rats, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.
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