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Cited by 66SARS-CoV-2 and COVID-19 ResearchVaccine Coverage and HesitancyCOVID-19 Clinical Research Studies

An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial

Open access
Saraf, Amit, Gurjar, Rohan, Kaviraj, Swarnendu, Kulkarni, Aishwarya, Kumar, Durgesh, Kulkarni, Ruta, Virkar, Rashmi, Krishnan, Jayashri +28 more·2024·Nature Medicine
DOI 10.1038/s41591-024-02955-2PMC PMC11108772
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Abstract

Here we conducted a multicenter open-label, randomized phase 2 and 3 study to assess the safety and immunogenicity of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-specific (BA.1/B.1.1.529), monovalent, thermostable, self-amplifying mRNA vaccine, GEMCOVAC-OM, when administered intradermally as a booster in healthy adults who had received two doses of BBV152 or ChAdOx1 nCoV-19. GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3. In phase 2, the safety and immunogenicity of GEMCOVAC-OM was compared with our prototype mRNA vaccine GEMCOVAC-19 (D614G variant-specific) in 140 participants. At day 29 after vaccination, there was a significant rise in anti-spike (BA.1) IgG antibodies with GEMCOVAC-OM ( P < 0.0001) and GEMCOVAC-19 ( P < 0.0001). However, the IgG titers (primary endpoint) and seroconversion were higher with GEMCOVAC-OM ( P < 0.0001). In phase 3, GEMCOVAC-OM was compared with ChAdOx1 nCoV-19 in 3,140 participants (safety cohort), which included an immunogenicity cohort of 420 participants. At day 29, neutralizing antibody titers against the BA.1 variant of SARS-CoV-2 were significantly higher than baseline in the GEMCOVAC-OM arm ( P < 0.0001), but not in the ChAdOx1 nCoV-19 arm ( P = 0.1490). GEMCOVAC-OM was noninferior (primary endpoint) and superior to ChAdOx1 nCoV-19 in terms of neutralizing antibody titers and seroconversion rate (lower bound 95% confidence interval of least square geometric mean ratio >1 and difference in seroconversion >0% for superiority). At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM ( P < 0.0001). These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant. Clinical Trial Registry India identifier: CTRI/2022/10/046475 .

AI snapshot

Written from the paper’s full text.

TL;DR

GEMCOVAC-OM, an Omicron BA.1-specific, monovalent, thermostable self-amplifying mRNA booster, was safe and immunogenic in a phase 2/3 randomized trial. In phase 3, it was noninferior and superior to ChAdOx1 nCoV-19 for neutralizing antibody titers and seroconversion against BA.1 at day 29.

Key findings

  • In phase 2 (n = 140), anti-spike IgG GMT rose from 30,048 (95% CI 23,910–37,763) at baseline to 244,440 (95% CI 229,122–260,782) at day 29 with GEMCOVAC-OM (P < 0.0001); GMFR was 8.13 versus 2.12 for GEMCOVAC-19, and LSGMR was 3.40 (95% CI 2.79–4.13, P < 0.0001). Seroresponse was 92.9% with GEMCOVAC-OM versus 57.1% with GEMCOVAC-19.
  • In phase 3, neutralizing antibody GMT against BA.1 rose from 623.9 (95% CI 533.3–729.9) to 1,099.9 (95% CI 1,000.0–1,209.9) at day 29 with GEMCOVAC-OM (P < 0.0001), but not with ChAdOx1 nCoV-19 (775.3 to 754.9; P = 0.1490). LSGMR was 1.58 (95% CI 1.36–1.84), and seroconversion was 39.5% versus 19.5% (difference 19.93, 95% CI 10.57–28.43).
  • Safety: in phase 3, 602 participants (20.1%) in the GEMCOVAC-OM arm and 33 (24.8%) in the ChAdOx1 nCoV-19 arm reported at least one AE; most were mild. No vaccine-related serious AEs or deaths were reported.
  • Cellular responses at day 29 were higher with GEMCOVAC-OM than ChAdOx1 nCoV-19 for TNF+CD4+, IL-2+CD4+ and IL-2+CD8+ T cells (P < 0.0001 for the latter comparisons reported).

Methods

  • Multicenter, open-label, randomized phase 2 seamlessly followed by phase 3 in healthy adults ≥18 years who had received two doses of BBV152 or ChAdOx1 nCoV-19 at least 4 months before screening. Phase 2 randomized 140 participants 1:1 to GEMCOVAC-OM or GEMCOVAC-19; phase 3 had a safety cohort of 3,140 (3,000 GEMCOVAC-OM; 140 ChAdOx1 nCoV-19) and an immunogenicity cohort of 420 (280 GEMCOVAC-OM; 140 ChAdOx1 nCoV-19).
  • GEMCOVAC-OM 10 µg in 0.1 ml was given intradermally via the Tropis needle-free injection system; ChAdOx1 nCoV-19 was given intramuscularly; GEMCOVAC-19 10 µg in 0.5 ml was given intramuscularly. Immunogenicity was assessed by PRNT50, anti-spike IgG ELISA, cPass, intracellular cytokine staining and B cell flow cytometry; safety was assessed through solicited AEs to day 7 and unsolicited AEs through day 180.
  • Primary phase 3 endpoint was noninferiority of neutralizing antibody GMT by PRNT50 and seroconversion difference at day 29, analyzed in the full analysis set using ANCOVA with baseline titers as covariates and the Miettinen–Nurminen method; noninferiority margins were >0.67 for LSGMR and >−10% for seroconversion difference, with superiority criteria >1 and >0%.

Limitations

  • The paper states that participants were predominantly male; the comparator in phase 3 was ChAdOx1 nCoV-19 (Wuhan strain) rather than an Omicron-specific mRNA vaccine because those were not approved or available in India; blinding was not possible due to different delivery mechanisms; accurate past COVID-19 infection data could not be obtained; and an efficacy study was not possible, so an immunobridging approach was used.
  • The paper also states that the sex-disaggregated analysis was not powered and that no formal sample size calculation was performed for phase 2.
  • Evident from the text: the phase 3 immunogenicity cohort was a subset of the safety cohort, and the open-label design may introduce bias in safety assessment, as the authors note.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41591-024-02955-2

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

28 of 35 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The BA.1 Omicron variant evaded immunity acquired from vaccines designed against the ancestral strain.

    “The BA.1 (B.1.1.529) Omicron variant, first identified in Botswana, became dominant worldwide quickly and was seen to evade immunity acquired from vaccines that were designed against the ancestral strain4.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Planas, D. et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 602, 671–675 (2022). source

      The paper identifies the tested isolate as BA.1 (Isolation and characterization of an Omicron variant) and reports that it escaped vaccine-elicited antibodies to a large extent (opening summary; Sensitivity of Omicron to sera from vaccinees). The evidence concerns antibody neutralization, particularly five months after two vaccine doses; it does not establish escape from vaccine-acquired immunity as a whole, and the paper reports a neutralizing response after a booster. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    The BA.1 Omicron variant became dominant worldwide quickly.

    “The BA.1 (B.1.1.529) Omicron variant, first identified in Botswana, became dominant worldwide quickly and was seen to evade immunity acquired from vaccines that were designed against the ancestral strain4.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Planas, D. et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 602, 671–675 (2022). source

      The paper’s opening passage says Omicron had spread to many countries and was expected to rapidly become dominant worldwide; it does not say that worldwide dominance had already occurred. The Discussion likewise describes rapid spread in different countries. The copy identifies the studied strain as BA.1, but the claim turns a prediction into an accomplished event. Page numbers were not provided. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    Self-amplifying mRNA vaccines can lower the dose for administration.

    “First, GEMCOVAC-OM is a self-amplifying mRNA (samRNA) vaccine, which can lower the dose for administration6.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [6] Comes, J. D. G., Pijlman, G. P. & Hick, T. A. H. Rise of the RNA machines—self-amplification in mRNA vaccine design. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2023.05.007 (2023). source
  • Premisecitation

    GEMCOVAC-OM is a self-amplifying mRNA (samRNA) vaccine.

    “First, GEMCOVAC-OM is a self-amplifying mRNA (samRNA) vaccine, which can lower the dose for administration6.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] Comes, J. D. G., Pijlman, G. P. & Hick, T. A. H. Rise of the RNA machines—self-amplification in mRNA vaccine design. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2023.05.007 (2023). source

      The mRNA vaccine landscape section says self-amplifying RNA vaccines can induce protection at a markedly lower initial dose than conventional mRNA vaccines. The Safety considerations section describes an approved human replicon vaccine in India, but our copy does not name GEMCOVAC-OM or establish that it is a self-amplifying mRNA vaccine (searched: GEMCOVAC-OM, GEMCOVAC). (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    Thermostability is a critical factor in ensuring equitable access to effective mRNA vaccines in LMICs.

    “Thermostability is another critical factor in ensuring equitable access to effective mRNA vaccines in LMICs42.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [42] Lancet Commission on COVID-19 Vaccines and Therapeutics Task Force Members. Urgent needs of low-income and middle-income countries for COVID-19 vaccines and therapeutics. Lancet 397, 562–564 (2021). source
  • May combine two claims. 51
  • Classified as probably not a substantial claim. 42
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    mRNA vaccines are produced synthetically in a cell-free environment allowing scalable, cost-effective and rapid production.

    “Furthermore, mRNA vaccines are produced synthetically in a cell-free environment allowing a scalable, cost-effective and rapid production3.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Gote, V. et al. A comprehensive review of mRNA vaccines. Int. J. Mol. Sci. 24, 2700 (2023). source

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

    Premisecitation

    Live virus neutralization assays are considered the gold standard for assessing immune responses.

    “Live virus neutralization assays are considered to be the gold standard for assessing immune responses25.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [25] Bewley, K. R. et al. Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays. Nat. Protoc. 16, 3114–3140 (2021). source

      The Development of the protocol section calls the live-virus plaque reduction neutralization test (PRNT) the gold standard for assessing humoral correlates of protection for many viral diseases. The citing sentence broadens this to live-virus neutralization assays generally and to immune responses beyond the humoral response. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Neutralizing antibody response is considered a surrogate for efficacy against severe disease and has been used in immunobridging studies.

    “Neutralizing antibody response is considered to be a surrogate for efficacy against severe disease24 and has been used in immunobridging studies, especially for variant-updated COVID-19 vaccines20.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [24] 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
    • cites [20] Chalkias, S. et al. A bivalent Omicron-containing booster vaccine against Covid-19. N. Engl. J. Med. 387, 1279–1291 (2022). source

  • May combine two claims.

    Premisecitation

    Studies have shown that the intrinsic severity of the Omicron variant is similar to that of its predecessors and cross-reactive protection from vaccination and/or infection plays an important role in reducing the severity of Omicron-associated COVID-19.

    “Studies have shown that the intrinsic severity of the Omicron variant is similar to that of its predecessors and cross-reactive protection from vaccination and/or infection plays an important role in reducing the severity of Omicron-associated COVID-19 (ref. 27).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Wong, J. Y. et al. Intrinsic and effective severity of COVID-19 cases infected with the ancestral strain and Omicron BA.2 variant in Hong Kong. J. Infect. Dis. 228, 1231–1239 (2023). 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

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

    Interpretationcitation

    The absence of myocarditis signs or symptoms is expected given the incidence of 1-5 cases per 100,000 in the general population.

    “None of the participants reported any signs or symptoms of myocarditis that would warrant further investigation, which is expected given the incidence of 1–5 cases per 100,000 in the general population12.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Bozkurt, B. Shedding light on mechanisms of myocarditis with COVID-19 mRNA vaccines. Circulation 147, 877–880 (2023). source

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

    Interpretationcitation

    These findings are in line with real-world evidence on COVID-19 mRNA vaccines (BNT162b2, mRNA-1273) which describe higher reactogenicity in females compared with males.

    “These findings are in line with the real-world evidence on COVID-19 mRNA vaccines (BNT162b2, mRNA-1273) which describe higher reactogenicity in females compared with males38,39.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [38] Chapin-Bardales, J. et al. Reactogenicity within 2 weeks after mRNA COVID-19 vaccines: findings from the CDC v-safe surveillance system. Vaccine 39, 7066–7073 (2021). source
    • cites [39] Menni, C. et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect. Dis. 21, 939–949 (2021). source

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

    Premisecitation

    Marchevsky et al. found a small, statistically significant difference in anti-spike IgG titers, with higher titers in female participants, and twice as many systemic reactions reported by women.

    “These findings contrast with sex-disaggregated data published by Marchevsky et al.37 where a small, statistically significant difference was found in the anti-spike IgG titers, with higher titers in female participants and there were twice as many systemic reactions reported by women.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [37] Marchevsky, N. G. et al. An exploratory analysis of the response to ChAdOx1 nCoV-19 (AZD1222) vaccine in males and females. eBioMedicine 81, 104128 (2022). source

      The Results > Immunogenicity section reports a small, statistically significant increase in anti-spike IgG titres in females. The Results > Reactogenicity section reports nearly twice the adjusted odds of reporting any systemic reaction after the first dose (OR 1.95), not twice as many reactions; it found no significant sex difference in systemic reactions after the second dose. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Omicron variants, although more infective, are associated with lower rates of hospitalization and death compared with previous SARS-CoV-2 strains.

    “Omicron variants, although more infective, are associated with lower rates of hospitalization and death compared with previous SARS-CoV-2 strains.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Wong, J. Y. et al. Intrinsic and effective severity of COVID-19 cases infected with the ancestral strain and Omicron BA.2 variant in Hong Kong. J. Infect. Dis. 228, 1231–1239 (2023). source

      The Results (page unavailable) report lower case-hospitalization risk in Omicron-predominant wave 5 than in earlier waves for adults aged 45 and older. But they report higher fatality risk among hospitalized older adults in wave 5, while the Discussion finds Omicron BA.2 and the ancestral strain had similar intrinsic severity. The paper attributes lower effective severity to vaccination and does not establish the claim that Omicron variants are more infective. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    A specific subset of CD8+ T cells capable of intrinsic IL-2 expression exhibit stem-like characteristics, display a memory phenotype, can withstand exhaustion and effectively regulate chronic viral infections.

    “Kahan et al.33 have demonstrated that a specific subset of CD8+ T cells, capable of intrinsic IL-2 expression, exhibit stem-like characteristics, display a memory phenotype, can withstand exhaustion and effectively regulate chronic viral infections33.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [33] Kahan, S. M. et al. Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection. Sci. Immunol. 7, eabl6322 (2022). source

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

    Premisecitation

    A subset of individuals (approximately 21%) exhibited a more than 50% decrease in T cell reactivity to the Omicron spike.

    “However, a subset of individuals (approximately 21%) exhibited a more than 50% decrease in T cell reactivity to the Omicron spike28.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [28] Naranbhai, V. et al. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals. Cell https://doi.org/10.1016/j.cell.2022.03.022 (2022). source

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

    Premisecitation

    TH1 and TH2 cell responses support B cell activation and differentiation for antigen-specific antibody production and long-term memory development through germinal cell responses.

    “TH1 and TH2 cell responses support B cell activation and differentiation for antigen-specific antibody production and long-term memory development through germinal cell responses34,35.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [34] Graham, B. S. Rapid COVID-19 vaccine development. Science 368, 945–946 (2020). source
    • cites [35] Akkaya, M., Kwak, K. & Pierce, S. K. B cell memory: building two walls of protection against pathogens. Nat. Rev. Immunol. 20, 229–238 (2020). source

      The Phase 1 section on antigen-driven differentiation of naive B cells says that T-helper-cell interactions support pathogen-specific antibody production and germinal-centre B-cell differentiation into long-lived plasma cells and memory B cells. It identifies T follicular helper (TFH) cells as providing crucial help in germinal centres, however, not TH1 and TH2 responses specifically. The named cell subsets are therefore not supported by this source. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    IFNγ co-operates with other TH1 cell cytokines and acts synergistically to enhance their ability to eliminate pathogens.

    “It is worth noting that IFNγ co-operates with other TH1 cell cytokines and acts synergistically to enhance their ability to eliminate pathogens31,32.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [31] Bogdan, C., Moll, H., Solbach, W. & Röllinghoff, M. Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes. Eur. J. Immunol. 20, 1131–1135 (1990). source

      Section 3.2 reports a synergistic anti-parasitic effect of IFN-γ and TNF-α: together they reduced L. major parasites in murine macrophages when either cytokine alone was ineffective at the tested doses. The Concluding remarks suggest this synergy may matter for protection against other intracellular parasites, but the paper does not establish synergy with TH1 cytokines generally or elimination of pathogens generally. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [32] Liew, F. Y., Li, Y. & Millott, S. Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. J. Immunol. 145, 4306–4310 (1990). source

  • May combine two claims.

    Premisecitation

    samRNA vaccines can induce potent immune responses at lower doses due to their ability to amplify antigen production within the body, potentially reducing the risk of adverse reactions.

    “samRNA vaccines can induce potent immune responses at lower doses due to their ability to amplify antigen production within the body, potentially reducing the risk of adverse reactions6,44.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [6] Comes, J. D. G., Pijlman, G. P. & Hick, T. A. H. Rise of the RNA machines—self-amplification in mRNA vaccine design. Trends Biotechnol. https://doi.org/10.1016/j.tibtech.2023.05.007 (2023). source
    • cites [44] 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). source

      The “Self-amplifying mRNA vaccines” section says intracellular RNA replication enables substantial antigen production from very small doses and reports potent immune responses at low doses. It does not say this reduces adverse reactions; instead, it warns that SAM vaccines’ inflammatory profile or reactogenicity may be difficult to modulate. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3.

    “GEMCOVAC-OM was well tolerated with no related serious adverse events in both phase 2 and phase 3.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Three participants from the GEMCOVAC-OM arm reported serious AEs of omphalitis, spontaneous abortion and pulmonary tuberculosis, while one participant who received ChAdOx1 nCoV-19 suffered a ligament rupture.

    “Three participants from the GEMCOVAC-OM arm reported serious AEs of omphalitis, spontaneous abortion and pulmonary tuberculosis, while one participant who received ChAdOx1 nCoV-19 suffered a ligament rupture.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ChAdOx1 nCoV-19 showed a significant positive correlation between TNF-expressing CD4+ and CD8+ T cells (P < 0.05) as well as IL-2+CD4+ and IL-2+CD8+ T cells (P < 0.0001).

    “ChAdOx1 nCoV-19 also showed a significant positive correlation between TNF-expressing CD4+ and CD8+ T cells (P < 0.05) as well as IL-2+CD4+ and IL-2+CD8+ T cells (P < 0.0001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At day 90, Omicron B.1.1.529-specific B cells in the GEMCOVAC-OM study group were similar to baseline level but significantly higher than ChAdOx1 nCoV-19 (P = 0.0157).

    “However, at day 90, Omicron B.1.1.529-specific B cells in the GEMCOVAC-OM study group were similar to baseline level but significantly higher than ChAdOx1 nCoV-19 (P = 0.0157).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    At day 29, seroconversion (secondary endpoint) was significantly higher with GEMCOVAC-OM than ChAdOx1 nCoV-19 (P < 0.0001).

    “At day 29, anti-spike IgG antibodies and seroconversion (secondary endpoints) were significantly higher with GEMCOVAC-OM (P < 0.0001).”
    • Also stated in: § Humoral Immunogenicity · plain
      “Seroresponse in terms of anti-spike IgG antibodies were higher with GEMCOVAC-OM (93.0%) compared with ChAdOx1 nCoV-19 (76.7%) with a difference of 16.30 (95% CI 9.02–24.64, P < 0.0001; Supplementary Table 6).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In phase 3, there was a statistically significant increase in IFNγ+CD4+ T cells from participants vaccinated with ChAdOx1 nCoV-19 (P < 0.0001) and in IL-2+CD4+ T cells from recipients of GEMCOVAC-OM (P < 0.0001) from baseline to day 29.

    “There was a statistically significant increase in IFNγ+CD4+ T cells from participants vaccinated with ChAdOx1 nCoV-19 (P < 0.0001) and in IL-2+CD4+ T cells from recipients of GEMCOVAC-OM (P < 0.0001) from baseline to day 29.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the GEMCOVAC-OM group, there were no significant differences in neutralizing antibodies at day 29 and anti-spike IgG antibodies at days 29 and 90 between female and male participants.

    “Similarly, in the GEMCOVAC-OM group, there were no significant difference in the neutralizing antibodies at day 29 and anti-spike IgG antibodies at days 29 and 90 between female and male participants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At day 90, TNF+CD4+ T cells (P = 0.0055) and IL-2+CD8+ T cells (P = 0.0271) were higher with GEMCOVAC-OM compared with GEMCOVAC-19.

    “At day 90, TNF+CD4+ T cells (P = 0.0055) and IL-2+CD8+ T cells (P = 0.0271) were higher with GEMCOVAC-OM compared with GEMCOVAC-19.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In phase 2, GEMCOVAC-19 and GEMCOVAC-OM showed a significant increase in IFNγ+CD8+ T cells (P = 0.0004 and P = 0.0009 respectively) and IL-2+CD8+ T cells (P = 0.0002 and P = 0.0001, respectively) from baseline to day 29.

    “In terms of CD8+ T cells, GEMCOVAC-19 and GEMCOVAC-OM showed a significant increase in IFNγ+CD8+ T cells (P = 0.0004 and P = 0.0009 respectively) and IL-2+CD8+ T cells (P = 0.0002 and P = 0.0001, respectively) from baseline to day 29.”
    Quote in the paperSubstantial claim

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

    Findingown data

    In both vaccine arms, women had numerically higher neutralizing and anti-spike IgG antibody titers at baseline compared with men.

    “In both the vaccine arms, women had numerically higher neutralizing and anti-spike IgG antibody titers at baseline compared with men.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In phase 2, no unsolicited events or serious AEs were reported till the end of the study.

    “No unsolicited events or serious AEs were reported till the end of the study.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    GEMCOVAC-OM displayed a significant increase in B.1.1.529 spike-specific B cells compared with baseline (P = 0.0013) and ChAdOx1 nCoV-19 at day 29 (P < 0.0001).

    “GEMCOVAC-OM displayed a significant increase in B.1.1.529 spike-specific B cells compared with baseline (P = 0.0013) and ChAdOx1 nCoV-19 at day 29 (P < 0.0001; Fig. 3g).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    GEMCOVAC-OM showed significantly higher Omicron B.1.1.529-reactive TNF+CD4+ (P < 0.001), IL-2+CD4+ (P < 0.0001) and IL-2+CD8+ (P < 0.0001) T cells compared with ChAdOx1 nCoV-19.

    “GEMCOVAC-OM showed significantly higher Omicron B.1.1.529-reactive TNF+CD4+ (P < 0.001), IL-2+CD4+ (P < 0.0001) and IL-2+CD8+ (P < 0.0001) T cells compared with ChAdOx1 nCoV-19 (Fig. 3a–f).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Significant positive correlations between IL-2-expressing CD4+ and CD8+ T cells (P < 0.0001) as well as IFNγ+CD8+ and IL-2+CD8+ T cells (P < 0.05) were observed with GEMCOVAC-OM.

    “Significant positive correlations between IL-2-expressing CD4+ and CD8+ T cells (P < 0.0001) as well as IFNγ+CD8+ and IL-2+CD8+ T cells (P < 0.05) were also observed with GEMCOVAC-OM.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At day 90, GEMCOVAC-19 and GEMCOVAC-OM had significantly higher IFNγ+CD4+ T cells (P = 0.001 and P = 0.0465, respectively) and IFNγ+CD8+ T cells (P = 0.0002 and P = 0.0027, respectively) compared with baseline.

    “Additionally, at day 90, GEMCOVAC-19 and GEMCOVAC-OM had significantly higher IFNγ+CD4+ T cells (P = 0.001 and P = 0.0465, respectively) and IFNγ+CD8+ T cells (P = 0.0002 and P = 0.0027, respectively) compared with baseline.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In phase 3, GMFR in neutralizing antibodies for GEMCOVAC-OM and ChAdOx1 nCoV-19 were 1.76 and 0.97, respectively.

    “GMFR in neutralizing antibodies for GEMCOVAC-OM and ChAdOx1 nCoV-19 were 1.76 and 0.97, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In phase 2, the geometric mean fold rise in anti-spike IgG antibodies was 8.13 for GEMCOVAC-OM and 2.12 for GEMCOVAC-19.

    “The geometric mean fold rise (GMFR, post-booster/prebooster vaccination) in anti-spike IgG antibodies for GEMCOVAC-OM and GEMCOVAC-19 was 8.13 and 2.12, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In phase 2, there were a total of 14 AEs, 5 in GEMCOVAC-OM and 9 in GEMCOVAC-19.

    “In phase 2, there were a total of 14 AEs of which 5 occurred in participants who received GEMCOVAC-OM and 9 in those who received GEMCOVAC-19 (Supplementary Table 4).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A significant positive correlation between anti-spike IgG (binding) antibody titers and neutralizing antibody titers was observed with GEMCOVAC-OM, but not with ChAdOx1 nCoV-19.

    “A significant positive correlation between anti-spike IgG (binding) antibody titers and neutralizing antibody titers was observed with GEMCOVAC-OM, but not with ChAdOx1 nCoV-19.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In phase 3, GEMCOVAC-OM showed an increase in IFNγ+CD8+ T cells from baseline to day 29 and a significantly higher expression of TNF+CD4+, IL-2+CD4+ and IL-2+CD8+ T cells at day 29 compared with ChAdOx1 nCoV-19.

    “Similarly, in phase 3, GEMCOVAC-OM showed an increase in IFNγ+CD8+ T cells from baseline to day 29 and a significantly higher expression of TNF+CD4+, IL-2+CD4+ and IL-2+CD8+ T cells at day 29 compared with ChAdOx1 nCoV-19.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most of the AEs were mild to moderate and resolved on their own.

    “Most of the AEs were mild to moderate and resolved on their own.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At day 90, GEMCOVAC-OM showed significantly higher TNF+CD4+, IL-2+CD4+ and IL-2+CD8+ T cells compared with ChAdOx1 nCoV-19 (phase 3).

    “Additionally, at day 90, GEMCOVAC-OM showed significantly higher TNF+CD4+ T cells and IL-2+CD8+ T cells compared with GEMCOVAC-19 (phase 2) and higher TNF+CD4+, IL-2+CD4+ and IL-2+CD8+ T cells compared with ChAdOx1 nCoV-19 (phase 3), indicating a durable T cell protection with BA.1-specific vaccine.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In both arms, the percentage neutralization was >90%, which is representative of high neutralization activity.

    “In both arms, the percentage neutralization was >90%, which is representative of high neutralization activity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No vaccine-related serious AEs or deaths were reported.

    “No vaccine-related serious AEs or deaths were reported.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At day 90, neutralizing antibodies further dropped in the ChAdOx1 nCoV-19 group while titers in the GEMCOVAC-OM group returned to levels close to baseline (GMFR 1.21).

    “Furthermore, at day 90, the neutralizing antibodies further dropped in the ChAdOx1 nCoV-19 group while the titers in the GEMCOVAC-OM group returned to levels close to the baseline (GMFR 1.21).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    GEMCOVAC-OM showed a 1.76-fold increase in neutralizing antibody titers against Omicron BA.1, while no significant change in neutralization titers was observed with ChAdOx1 nCoV-19 when administered as a booster.

    “Consequently, GEMCOVAC-OM showed a 1.76-fold increase in neutralizing antibody titers against Omicron BA.1, while no significant change in the neutralization titers was observed with ChAdOx1 nCoV-19, when administered as a booster.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no significant differences in neutralizing and anti-spike IgG titers between men and women receiving GEMCOVAC-OM, except at day 29, where neutralizing titers were significantly higher in women.

    “There were no significant differences in the neutralizing and anti-spike IgG titers between men and women receiving GEMCOVAC-OM, except at day 29, where neutralizing titers were significantly higher in women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    GEMCOVAC-OM is a lyophilized vaccine and can be transported and stored at 2-8 °C for 12 months, facilitating democratization of access to vaccine.

    “GEMCOVAC-OM is a lyophilized vaccine and can be transported and stored at 2–8 °C for 12 months, facilitating democratization of access to vaccine.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    In phase 3, 14 participants had already received a booster vaccine for COVID-19 and were excluded from the safety and immunogenicity analysis.

    “After vaccination on day 1, it was found that 14 participants (9 in GEMCOVAC-OM arm and 5 in ChAdOx1 nCoV-19 arm) had already received a booster vaccine for COVID-19. This was a major protocol deviation and, hence, these participants were excluded from the safety and immunogenicity analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    GEMCOVAC-OM is a monovalent, Omicron-specific (BA.1) booster mRNA vaccine for COVID-19.

    “we developed GEMCOVAC-OM, a monovalent, Omicron-specific (BA.1) booster mRNA vaccine for COVID-19 (ref. 5).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Wadapurkar, R., Singh, S. & Singh, A. Leveraging the immunoinformatics approach for designing the SARS-CoV-2 Omicron-specific antigenic cassette of mRNA vaccine. Vaccine 42, 1630–1647 (2024). source

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

    Study design and conductown data

    The median age of participants was comparable in both phase 2 and phase 3 arms.

    “The median age of participants was comparable in both phase 2 (GEMCOVAC-OM: 32 years and GEMCOVAC-19: 30 years) and phase 3 (32 years in both GEMCOVAC-OM and ChAdOx1 nCoV-19 arms).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    In phase 2, all 140 individuals completed the study up to the day 180 follow-up.

    “All 140 individuals completed the study up to the day 180 follow-up.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    There were considerably more men than women in both phase 2 and phase 3.

    “Of note, there were considerably more men in both phase 2 (87.1% in GEMCOVAC-OM and 91.4% in GEMCOVAC-19) and phase 3 (68.2% in GEMCOVAC-OM and 79.7% in ChAdOx1 nCoV-19).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    In phase 2, 140 participants were randomized to either GEMCOVAC-OM or GEMCOVAC-19.

    “In the phase 2 study, 140 participants were randomized to either GEMCOVAC-OM or the prototype vaccine GEMCOVAC-19, which was designed against the D614G variant of SARS-CoV-2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant.

    “These results demonstrate that GEMCOVAC-OM is safe and boosts immune responses against the B.1.1.529 variant.”
    • Also stated in: § Discussion · plain
      “GEMCOVAC-OM was found to be safe and well tolerated and generated significant humoral as well as cellular immune responses against the B.1.1.529 variant.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    In phase 3, the day 29 visit was completed by 3,119 participants, of which 404 were included in the primary immunogenicity endpoint.

    “The day 29 visit was completed by 3,119 participants of which 404 (271 in the GEMCOVAC-OM arm and 133 in ChAdOx1 nCoV-19 arm) were included in the primary immunogenicity endpoint.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The absence of a needle obviates challenges of need for sharps disposal, needle-stick injuries, cross-contamination and needle phobia.

    “Additionally, the absence of a needle obviates challenges of need for sharps disposal, needle-stick injuries, cross-contamination and needle phobia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The cPass results are in contrast with the neutralization assessed using PRNT50 assay and may be due to differences in the assays.

    “These results are in contrast with the neutralization assessed using PRNT50 assay and may be due to differences in the assays.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: cPass is a semi-quantitative assay with an upper limit cutoff of 100%, so differences beyond the cutoff cannot be observed.

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

    Interpretationreasoning

    Differences in the vaccines beyond the cutoff cannot be observed.

    “Differences in the vaccines beyond the cutoff cannot be observed.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: cPass is a semi-quantitative assay with an upper limit cutoff of 100%, so differences beyond the cutoff cannot be observed.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    cPass is a semi-quantitative assay and has an upper limit cutoff of 100%.

    “cPass is a semi-quantitative assay and has an upper limit cutoff of 100%.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: cPass is a semi-quantitative assay with an upper limit cutoff of 100%, so differences beyond the cutoff cannot be observed.

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

    Interpretationnone given

    Differences in study design and populations (sample size, primary versus booster vaccination, and ethnicity) between the two studies can have a substantial impact on outcomes.

    “However, it is important to note that there were many differences in the study design and the populations (sample size, primary versus booster vaccination, and ethnicity) assessed in these two studies that can have a substantial impact on outcomes.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Vaccine-induced CD8+ T cell responses are important for long-term immunity and should be considered as a correlate of protection.

    “Recent findings have shown that vaccine-induced CD8+ T cell responses are important for long-term immunity and should also be considered as a correlate of protection29,30.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Antoun, E., Peng, Y. & Dong, T. Vaccine-induced CD8+ T cells are key to protection from SARS-CoV-2. Nat. Immunol. 24, 1594–1596 (2023). source
    • cites [30] Painter, M. M. et al. Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection. Nat. Immunol. 24, 1711–1724 (2023). source

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Live virus neutralization is considered to be the gold standard of immunogenicity assessment and a correlate of protection.

    “Importantly, live virus neutralization is considered to be the gold standard of immunogenicity assessment and a correlate of protection.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Live virus neutralization is the gold standard of immunogenicity assessment and a correlate of protection.

  • May combine two claims.

    Study design and conductnone given

    The study participants were predominantly male, and as such, the results may be more representative of men than women.

    “The study participants were predominantly male, and as such, the results may be more representatives of men than women.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In adults, women have shown to mount higher immune responses than men and are more likely to report adverse reactions.

    “In adults, women have shown to mount higher immune responses than men and are more likely to report adverse reactions36.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Flanagan, K. L., Fink, A. L., Plebanski, M. & Klein, S. L. Sex and gender differences in the outcomes of vaccination over the life course. Annu. Rev. Cell Dev. Biol. 33, 577–599 (2017). source

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

    Interpretationnone given

    Baseline neutralizing titers in this study were already high and could potentially impact the boosting ability of the vaccines.

    “It is important to note that the baseline neutralizing titers in this study were already high and could potentially impact the boosting ability of the vaccines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    An efficacy study was not possible and hence an immunobridging approach was used.

    “An efficacy study was not possible and, hence, an immunobridging approach was used.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: At the time of the study, booster vaccines were approved in India.

  • May combine two claims.

    Study design and conductreasoning

    Blinding of participants in the study was not possible due to different mechanisms of delivery, which has the potential to introduce bias in the safety assessment.

    “Blinding of participants in the study was not possible due to the different mechanisms of delivery, which has the potential to introduce a bias in the safety assessment.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The self-amplifying, thermostable mRNA platform delivered intradermally provides a framework for next-generation vaccines that can improve accessibility and global equity.

    “This self-amplifying, thermostable mRNA platform delivered intradermally provides a framework for next-generation vaccines that can improve accessibility and global equity.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The trial is registered with Clinical Trial Registry India, CTRI/2022/10/046475.

    “This clinical trial is registered with the Clinical Trial Registry India, CTRI/2022/10/046475.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The study protocol was approved by the local ethics committee at each study site and Central Drugs Standard Control Organisation.

    “The study protocol was approved by the local ethics committee at each study site and Central Drugs Standard Control Organisation, the central licensing authority in India.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The final randomization list was filed securely by the independent biostatistician and accessible to authorized persons only.

    “The final randomization list was filed securely by the independent biostatistician and accessible to authorized persons only.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    In phase 2, participants were randomized to receive vaccines in a 1:1 ratio.

    “Participants were randomized to receive the vaccines in a 1:1 ratio.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Phase 2 safety data till day 7 were analyzed and presented to an independent DSMB, which approved initiation of phase 3.

    “In this seamless study, phase 2 safety data till day 7 were analyzed and presented to an independent DSMB. The DSMB evaluated these data and provided their approval to initiate the phase 3 part of the study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All immunogenicity analysis was performed in the full analysis set (intention to treat) population.

    “All immunogenicity analysis was performed in the full analysis set (intention to treat) population.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Eligible participants provided signed informed consent forms at enrollment.

    “Eligible participants provided signed informed consent forms at enrollment.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    In phase 3, the immunogenicity cohort was randomized in a 2:1 ratio into GEMCOVAC-OM and ChAdOx1 nCoV-19 by stratified block randomization through the IWRS.

    “In phase 3, consecutive 420 in the immunogenicity cohort were randomized in a 2:1 ratio into GEMCOVAC-OM and ChAdOx1 nCoV-19 by stratified block randomization through the IWRS.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Randomization codes were generated through Proc Plan using SAS version 9.4 or higher by an independent biostatistician.

    “The randomization codes were generated through Proc Plan using SAS version 9.4 or higher (SAS Institute) by an independent biostatistician.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Although the trial was open-label, laboratory analysis was conducted in a blinded manner.

    “Although the trial was open-label, laboratory analysis was conducted in a blinded manner.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    No formal sample size calculations were performed for phase 2.

    “No formal sample size calculations were performed for phase 2.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Participants were randomized using the interactive web response system (IWRS).

    “Participants who met the inclusion criteria and successfully completed all screening procedures were randomized in the study by using the interactive web response system (IWRS).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    RT-PCR positive participants were excluded from the immunogenicity analysis to avoid confounding.

    “Those found to be RT–PCR positive would be excluded from the immunogenicity analysis to avoid confounding.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Phase 3 was conducted at 20 hospitals in 13 cities across India in compliance with Declaration of Helsinki and ICH GCP.

    “The phase 3 study was conducted at 20 hospitals in 13 cities across India in compliance with the principles defined in the Declaration of Helsinki, International Conference for Harmonisation Good Clinical Practice Guideline.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The study was open-label and no masking was performed.

    “This was an open-label study, and no masking was performed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The samRNA platform used for GEMCOVAC-OM offers a promising avenue for effective and safe immunization against infectious diseases.

    “Lastly, the samRNA platform used for GEMCOVAC-OM offers a promising avenue for effective and safe immunization against infectious diseases.”
    Quote in the paperNot a substantial claim
78 of 78

  • The paper relies on this without support.

    GEMCOVAC-OM is lyophilized and stable at 2–8 °C for 12 months.

    “Second, GEMCOVAC-OM is lyophilized and stable at 2–8 °C for 12 months.”

  • The paper relies on this without support.

    Access to mRNA-based vaccines is a challenge, especially for LMICs, because transport and storage require a subzero temperature cold chain and such infrastructure is not readily available and is costly to implement.

    “Notwithstanding these advantages, access to mRNA-based vaccines has been a challenge, especially for low- to middle-income countries (LMICs). The transport and storage of mRNA vaccines require a subzero temperature cold chain. Such infrastructure is not readily available in LMICs and is costly to implement.”

  • The paper relies on this without support.

    Live virus neutralization is the gold standard of immunogenicity assessment and a correlate of protection.

    “Importantly, live virus neutralization is considered to be the gold standard of immunogenicity assessment and a correlate of protection.”

  • The paper relies on this without support.

    cPass is a semi-quantitative assay with an upper limit cutoff of 100%, so differences beyond the cutoff cannot be observed.

    “cPass is a semi-quantitative assay and has an upper limit cutoff of 100%. Differences in the vaccines beyond the cutoff cannot be observed.”

  • The paper relies on this without support.

    An Omicron-adapted vaccine was needed to provide protection against the BA.1 variant.

    “An Omicron-adapted vaccine was needed to provide protection against this variant.”

  • The paper relies on this without support.

    Both IFNγ and TNF play crucial roles in controlling intracellular pathogen infections.

    “Both IFNγ and TNF play crucial roles in controlling intracellular pathogen infections.”

  • The paper relies on this without support.

    IL-2 serves various functions in the development of effector and memory CD8+ T cell responses.

    “IL-2 serves various functions in the development of effector and memory CD8+ T cell responses.”

  • The paper relies on this without support.

    B cell responses play an important role in generating durable immunity.

    “In addition to T cell responses, B cell responses play an important role in generating durable immunity.”

  • The paper relies on this without support.

    The mRNA vaccines from Moderna and Pfizer were not approved or available in India.

    “However, the mRNA vaccines from Moderna and Pfizer were not approved or available in India due to which ChAdOx1 nCoV-19, which was designed against the ancestral spike (Wuhan), was used as a comparator.”

  • The paper relies on this without support.

    At the time of the study, booster vaccines were approved in India.

    “At the time of the study, booster vaccines were approved in India and, therefore, using a placebo as an arm in the clinical trial would have been unethical.”

  • The paper relies on this without support.

    The Tropis device has been well characterized and approved by numerous regulatory bodies including the World Health Organization.

    “The device has been well characterized and approved by numerous regulatory bodies including the World Health Organization.”

  • The paper relies on this without support.

    Each Tropis device can inject up to 20,000 vaccines, and the additional cost of the device is negligible and outweighed by advantages.

    “Each Tropis device can inject up to 20,000 vaccines, and the additional cost of the device is negligible and outweighed by advantages.”
12 of 12

Self-check

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

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

  • Sex-specific neutralizing antibody difference assigned to different visits

    Minor

    The Results state that women receiving GEMCOVAC-OM had significantly higher neutralizing antibody titers at day 90, but not day 29. The Discussion instead places the significant difference at day 29.

1 of 1

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Authors
Saraf, A., Gurjar, R., Kaviraj, S., Kulkarni, A., Kumar, D., Kulkarni, R., Virkar, R., Krishnan, J., Yadav, A., Baranwal, E., Singh, A., Raghuwanshi, A., Agarwal, P., Savergave, L., Singh, S., the GEMCOVAC-OM Study Investigators, Pophale, H., Shende, P., Shinde, R. B., Vikhe, V., Karmalkar, A., Deshmukh, B., Giri, K., Deshpande, S., Bulle, A., Siddiqui, M. S., Borthakur, S., Tummuru, V. R., Rao, A. V., Shukla, D., Jain, M. K., Bhardwaj, P., Supe, P. D., Das, M. K., Lahoti, M., & Barge, V.
Affiliations
  • Bharati Vidyapeeth (Deemed to be University) (IN)
  • JSS Medical Research (India) (IN)
  • ACE Hospital (IN)
  • Dr. D. Y. Patil Medical College, Hospital and Research Centre (IN)
  • All India Institute of Medical Sciences Raipur (IN)
  • St. Theresa’s Multi-Speciality Hospital (IN)
  • All India Institute of Medical Sciences Jodhpur (IN)
  • Rajarshee Chhatrapati Shahu Maharaj Government Medical College and CPR Hospital Kolhapur (IN)
Corresponding author
Singh, Sanjay
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2024-04-18
Volume
30
Issue
5
Pages
1363-1372
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-024-02955-2
PMC
PMC11108772
OpenAlex
W4394931432
Semantic Scholar
59a5344ebf4fd6e2cfa66af20b9d470fe6100fb6
Cited by
66
References
47
Citations by year
2026: 15 · 2025: 42 · 2024: 9
FWCI
21.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
Department of Biotechnology, Ministry of Science and Technology (BT/CS0002/CS/01/20)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
Omicron variant, SARS-CoV-2, self-amplifying mRNA vaccine, COVID-19 booster vaccination, ChAdOx1 nCoV-19 vaccine, intradermal vaccination, neutralizing antibodies, seroconversion, vaccine safety, immunogenicity, non-inferiority
MeSH terms
Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, ChAdOx1 nCoV-19, Adult, Antibodies, Viral, Female, Humans, Immunoglobulin G, Immunization, Secondary, Male, Middle Aged, Young Adult, 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.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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