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Cited by 82SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesSARS-CoV-2 detection and testing

Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial

Open access
Chen, Gui-Ling, Li, Xiao-Feng, Dai, Xia-Hong, Li, Nan, Cheng, Meng-Li, Huang, Zhen, Shen, Jian, Ge, Yu-Hua +23 more·2022·The Lancet Microbe
DOI 10.1016/s2666-5247(21)00280-9PMC PMC8786321
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Abstract

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.

AI snapshot

Written from the paper’s full text.

TL;DR

In a phase 1 trial in Chinese adults aged 18–59 years, the SARS-CoV-2 RBD mRNA vaccine ARCoV was safe and tolerated across 5–25 μg doses, with no serious adverse events and mostly mild or moderate reactions. It induced humoral and T-cell responses, and 15 μg produced the highest neutralising antibody titres, about twofold higher than convalescent COVID-19 sera.

Key findings

  • Among 120 randomised participants (20 per group), no serious adverse events were reported within 56 days. Fever was the most common systemic adverse reaction: 1 (5%) of 20 in the 5 μg group, 13 (65%) of 20 in the 10 μg group, 17 (85%) of 20 in the 15 μg group, 19 (95%) of 20 in the 20 μg group, and 16 (100%) of 16 in the 25 μg group (p<0·0001). Grade 3 systemic adverse events occurred in 0%, 15%, 30%, 35%, and 31% of the 5, 10, 15, 20, and 25 μg groups, respectively, versus 0% in placebo (p=0·0013).
  • After the second dose, RBD-specific IgG seroconversion at day 15 was 13 (65%) of 20 in the 5 μg group, 18 (90%) of 20 in the 10 μg group, 20 (100%) of 20 in the 15 μg group, 17 (85%) of 20 in the 20 μg group, and 13 (81%) of 16 in the 25 μg group; peak IgG geometric mean titre was 2414·8 ELISA units in the 15 μg group.
  • Pseudovirus neutralising antibody seroconversion at day 28 after the second dose was 85%, 90%, 100%, 95%, and 88% across the 5, 10, 15, 20, and 25 μg groups, respectively. Live SARS-CoV-2 neutralising antibody seroconversion at day 15 after the second dose was 80%, 90%, 95%, 95%, and 94%; the 15 μg group’s peak live-virus neutralising titre was about twofold higher than that of convalescent patients with COVID-19.
  • After the second vaccination, all participants in the 5, 10, 15, and 20 μg groups were positive for IFN-γ-expressing cells, and only one participant in the 25 μg group was negative; similar results were seen for IL-2-expressing cells.

Methods

  • Single-centre, double-blind, randomised, placebo-controlled, dose-escalation phase 1 trial at Shulan (Hangzhou) hospital, Hangzhou, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 were enrolled; 230 individuals were screened and 120 were randomly assigned 5:1 to ARCoV or placebo in five dose blocks (5, 10, 15, 20, and 25 μg), with two doses 28 days apart.
  • Safety outcomes included adverse events or reactions within 60 min and at days 7, 14, and 28 after each dose, plus laboratory abnormalities at days 1, 4, 7, and 28. Immunogenicity outcomes included anti-RBD IgG by ELISA, pseudovirus and live SARS-CoV-2 neutralising antibodies, and ELISpot IFN-γ/IL-2 T-cell responses.
  • Safety was assessed in all participants who received at least one dose; immunogenicity was assessed in the per-protocol population. Analyses used t tests or one-way ANOVA for means and Pearson χ² or Fisher’s exact tests for categorical outcomes; sample size was not based on statistical power calculations.

Limitations

  • The paper states that interpretation is based on a small sample size, that phase 2 and 3 data are needed, that the trial was restricted to Chinese adults aged 18–59 years with older-adult trials ongoing, and that long-term safety, tolerability, and immune persistence remain to be assessed.
  • Evident from the text: this was a single-centre phase 1 trial without an efficacy endpoint, and cellular immunogenicity was assessed only in the first 12 participants per group (ten vaccine, two placebo).

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

Integrity signals

Registry

Crossref · 10.1016/s2666-5247(21)00280-9

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

34 of 39 cited sources checked · 12 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    The receptor binding domain (RBD) of SARS-CoV-2 spike protein had been identified to play a key role in helping coronaviruses to enter human cells.

    “the receptor binding domain (RBD) of SARS-CoV-2 spike protein had been identified to play a key role in helping coronaviruses to enter human cells”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [8] Premkumar, 2020, The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients, Sci Immunol source
    • cites [9] Tai, 2020, A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2, Cell Res source
    • cites [10] Zang, 2020, Immunisation with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralising SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement, Cell Dis source
  • Premisecitation

    The RBD can induce strong humoral and cellular immune responses when used as an antigen in various SARS-CoV and MERS-CoV studies.

    “the RBD can induce strong humoral and cellular immune responses when used as an antigen in various SARS-CoV and MERS-CoV studies),8, 9, 10”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [8] Premkumar, 2020, The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients, Sci Immunol source

      The Results section on recombinant RBD antigens reports antibody binding in sera from animals immunized with SARS-CoV-1, but does not say they were immunized with RBD. The Study design describes using RBD to detect antibodies, not to induce immune responses. Searches for MERS-CoV and cellular immune responses found no passage addressing the claimed immunization findings. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [9] Tai, 2020, A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2, Cell Res source

      The introduction (page not supplied) says SARS-CoV and MERS-CoV RBDs were previously shown to be targets for effective vaccines. The paper reports humoral and T-cell responses to a SARS-CoV-2 RBD vaccine in mice, but does not state that the earlier SARS-CoV and MERS-CoV studies demonstrated both strong humoral and cellular responses. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [10] Zang, 2020, Immunisation with the receptor-binding domain of SARS-CoV-2 elicits antibodies cross-neutralising SARS-CoV-2 and SARS-CoV without antibody-dependent enhancement, Cell Dis source

      The paper’s opening passage (page unavailable) says SARS-CoV and MERS-CoV RBD proteins have been shown to induce protective neutralizing antibodies, supporting the humoral-response claim. It does not report cellular immune responses in those studies; its own immunization experiments also assess antibodies, not cellular immunity. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The incidence of grade 3 fever of ARCoV was similar to the trial results of another RBD-based mRNA vaccine, BNT162b1.

    “Thus, the incidence of grade 3 fever of ARCoV was similar to the trial results of another RBD-based mRNA vaccine, BNT162b1.16”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Li, 2021, Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomised, placebo-controlled, double-blind phase 1 study, Nat Med source

      The Preliminary safety and tolerability data section (article pp. 1062–1070) reports grade 3 fever in BNT162b1 recipients, including 17% of younger and 8% of older participants at the 30 µg dose. The discussion identifies BNT162b1 as an RBD-encoding vaccine. This paper does not report ARCoV's grade 3 fever incidence, so it cannot establish that the two incidences were similar. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The lack of immunogenicity improvement from 20 μg to 25 μg was similar to BNT162b1 and BNT162b2.

    “which was similar to BNT162b1 and BNT162b2.17”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [17] Walsh, 2020, Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates, New Engl J Med source

      The Immunogenicity section reports that the dose response from 20 to 30 µg was not consistent across the two vaccine candidates or age groups, and the Discussion describes an apparent plateau. The paper did not test 25 µg, and it does not establish a lack of improvement for both vaccines in every age group. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    Several studies have reported more frequent and severe solicited systemic adverse events following the second vaccination than we found.

    “Meanwhile, several studies17, 18, 19 have reported more frequent and severe solicited systemic adverse events following the second vaccination than we found.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [17] Walsh, 2020, Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates, New Engl J Med source
    • cites [18] Mulligan, 2020, Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults, Nature source

      The Results (p. 3) report that solicited systemic events affected more participants after the second BNT162b1 dose, and the Discussion says reactogenicity was generally higher after that dose. The paper does not compare its findings with the citing authors’ findings, so it cannot establish the claim’s “than we found” comparison; the passages also do not establish that systemic events were more severe after the second dose. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [19] Jackson, 2020, An mRNA vaccine against SARS-CoV-2—preliminary report, New Engl J Med source
  • May combine two claims. 34
  • Classified as probably not a substantial claim. 23
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    The incidence of grade 3 fever of BNT162b1 varied significantly in the same 30 μg group in adults aged 18-55 years, with none (0%) of 12 in the USA, one (8%) of 12 in Germany, and four (17%) of 24 in China, suggesting varying tolerability in different populations.

    “The incidence of grade 3 fever of BNT162b1 varied significantly in the same 30 μg group in adults aged 18–55 years, with none (0%) of 12 in the USA,17 one (8%) of 12 in Germany,18 and four (17%) of 24 in China,16 suggesting varying tolerability in different populations.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [16] Li, 2021, Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomised, placebo-controlled, double-blind phase 1 study, Nat Med source
    • cites [17] Walsh, 2020, Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates, New Engl J Med source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [18] Mulligan, 2020, Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults, Nature source

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

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Preclinical studies showed immunisation with ARCoV in a two-dose schedule elicited robust neutralising antibodies against SARS-CoV-2 as well as T-helper-1-biased cellular responses in mice and non-human primates.

    “Preclinical studies showed immunisation with ARCoV in a two-dose schedule, eliciting robust neutralising antibodies against SARS-CoV-2 as well as T-helper-1-biased cellular responses in mice and non-human primates.11”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] Zhang, 2020, A thermostable mRNA vaccine against COVID-19, Cell source

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

    Premisecitation

    The incidence of grade 3 fever of the two spike protein-based mRNA vaccines, mRNA-1273 and BNT162b2, also varied between the phase 1 and 3 trials.

    “Additionally, the incidence of grade 3 fever of the two spike protein-based mRNA vaccines, mRNA-127319, 20 and BNT162b2,17, 21 also varied between the phase 1 and 3 trials.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [19] Jackson, 2020, An mRNA vaccine against SARS-CoV-2—preliminary report, New Engl J Med source

      The Results > Vaccine Safety section reports one severe fever event after the second mRNA-1273 dose in this phase 1 trial. The Discussion says a phase 3 trial was anticipated, so this paper does not establish how grade 3 fever incidence varied between phase 1 and phase 3. It also does not report BNT162b2 trial results. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [20] Baden, 2021, Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine, New Engl J Med source

      The Safety section (p. 8) reports grade 3 systemic adverse events in the mRNA-1273 phase 3 trial, but does not identify the incidence of grade 3 fever. The Discussion (p. 11) says overall reactogenicity was similar to previously reported phase 1 data; it does not compare grade 3 fever incidence between phases. Searches for “grade 3 fever” and a phase 1–phase 3 fever comparison found no passage establishing the claimed variation. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [17] Walsh, 2020, Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates, New Engl J Med source

      The Introduction identifies this as a Phase 1 study of BNT162b2, and the Systemic events section reports fever rates after vaccination. It does not give an explicit incidence of grade 3 fever or compare that incidence with a Phase 3 trial. The separate citations attached to mRNA-1273 are outside this source's remit. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Interpretationown data

    The neutralising geometric mean titres about two times greater than convalescent sera show promising efficacy against COVID-19.

    “showing promising efficacy against COVID-19.22”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [22] Khoury, 2021, Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection, Nat Med source

      The Results (p. 2) find a strong relationship between neutralization levels relative to convalescent titers and vaccine efficacy, supporting the claim that such titers are promising. Our copy does not establish the specific claim that geometric mean titers about twice those of convalescent sera show efficacy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    The SARS-CoV-2 RBD was identified as the key antigen to induce a strong T-helper-1-biased cellular response.

    “The SARS-CoV-2 RBD was identified as the key antigen to induce a strong T-helper-1-biased cellular response.11”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Zhang, 2020, A thermostable mRNA vaccine against COVID-19, Cell source

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

    Premisecitation

    In humans, T cells contribute to the resolution of SARS-CoV infection and can form a long-lasting memory response to SARS-CoV up to 11 years post-infection in recovered patients.

    “In humans, T cells contribute to the resolution of SARS-CoV infection and can form a long-lasting memory response to SARS-CoV up to 11 years post-infection in recovered patients.27”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Ng, 2016, Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection, Vaccine source

      The Conclusion reports SARS-specific memory T cells in three recovered individuals at 9 and 11 years post-infection. The Introduction links lower T-cell numbers in humans with severe disease, but attributes evidence for T-cell-mediated viral clearance to animal studies; it does not establish that T cells contribute to resolution of infection in humans. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Among cytokine profiles of spike-responsive memory T cells, production was dominated by the expression of IL-2 and IFN-γ that were highly expressed by CCR6− subsets.

    “Among cytokine profiles of spike-responsive memory T cells, production was dominated by the expression of IL-2 and IFN-γ that were highly expressed by CCR6− subsets.32, 33”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [32] Ren, 2021, COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas, Cell source

      The Results section on cytokine storms reports high IFNG expression in a CD8 T-cell subtype, but does not identify it as spike-responsive or CCR6−. Searches for CCR6, spike-responsive memory T cells, and IL-2/IFN-γ production found no passage establishing the claimed cytokine profile; page numbers were unavailable in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [33] Rodda, 2021, Functional SARS-CoV-2-specific immune memory persists after mild COVID-19, Cell source

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

    Premisecitation

    SARS-CoV-2-specific memory T cells were detected in convalescent patients, even in exposed individuals who are seronegative.

    “and SARS-CoV-2-specific memory T cells were detected in convalescent patients, even in exposed individuals who are seronegative.30, 31”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [30] Canete, 2020, COVID-19 makes B cells forget, but T cells remember, Cell source
    • cites [31] Sekine, 2020, Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19, Cell source

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

    Premisecitation

    For SARS-CoV-2, increasing evidence indicates that T cells play a major role in the resolution of COVID-19.

    “For SARS-CoV-2, increasing evidence indicates that T cells play a major role in the resolution of COVID-19,28, 29”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [28] Liao, 2020, Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19, Nat Med source

      The Abstract and the main text report more highly expanded CD8+ T cells in moderate COVID-19 than in severe or critical cases, and suggest these findings may inform mechanisms of recovery. They do not establish that T cells play a major role in resolving COVID-19; the explicit statement about T cells being necessary for resolution concerns SARS-CoV infection in mice. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [29] Chen, 2020, T cell responses in patients with COVID-19, Nat Rev Immunol source

      The Conclusions (page unavailable) say accumulating evidence supports a role for T cells in COVID-19. But the Abstract says their role in resolving or exacerbating disease remains debated, and the CD8+ T cell section says an association with recovery may be a cause or a consequence. The source therefore does not establish a major role in resolution. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The incidence of grade 3 systemic adverse events was 0% in the 5 μg group, 15% in the 10 μg group, 30% in the 15 μg group, 35% in the 20 μg group, 31% in the 25 μg group, and 0% in the placebo group (p=0·0013).

    “The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Fever was the most common systemic adverse reaction, with incidence of 5% in the 5 μg group, 65% in the 10 μg group, 85% in the 15 μg group, 95% in the 20 μg group, and 100% in the 25 μg group (p<0·0001).

    “Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p<0·0001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19.

    “15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 34 serum specimens from patients with COVID-19 are representative of convalescent COVID-19 patients for comparing antibody titres.

  • May combine two claims.

    Findingown data

    Unsolicited adverse events related to vaccination were mild and moderate and mainly included infections (mostly urinary tract infections and upper respiratory tract infections), and kidney and urinary system diseases (mostly albuminuria).

    “Additionally, unsolicited adverse events related to vaccination were mild and moderate and mainly included infections (mostly urinary tract infections and upper respiratory tract infections), and kidney and urinary system diseases (mostly albuminuria).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The incidence of solicited adverse events was 60% in the 5 μg group, 80% in the 10 μg group, 95% in the 15 μg group, 95% in the 20 μg group, 100% in the 25 μg group, compared with 5% in the placebo group.

    “The incidence of solicited adverse events was 12 (60%) of 20 in the 5 μg group, 16 (80%) of 20 in the 10 μg group, 19 (95%) of 20 in the 15 μg group, 19 (95%) of 20 in the 20 μg group, and 16 (100%) of 16 in the 25 μg group, compared with one (5%) of 20 in the placebo group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A two-dose immunisation schedule (on days 0 and 28) with three of the five doses trialled (5 μg, 10 μg, 15 μg) elicited a time-dependent and dose-dependent neutralising antibody response (100% in the 15 μg group) and T-cell response (100% in the 15 μg group).

    “A two-dose immunisation schedule (on days 0 and 28) with three of the five doses trialled (5 μg, 10 μg, 15 μg) elicited a time-dependent and dose-dependent neutralising antibody response (100% in the 15 μg group) and T-cell response (100% in the 15 μg group).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter.

    “Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most reported adverse reactions were mild or moderate in severity and about 95% resolved in the first 2 days after first or second vaccinations; the remaining resolved within 5 days.

    “Most reported adverse reactions were mild or moderate in severity and about 95% resolved in the first 2 days after first or second vaccinations: the remaining resolved within 5 days.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or placebo (20 per group).

    “Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the 5 μg, 10 μg, and 15 μg groups, geometric mean titres of the pseudovirus 50% neutralising antibodies significantly increased by day 15 and peaked at day 28 after the second vaccination, whereas in the 20 μg and 25 μg groups, titres peaked at day 15 then declined slightly at day 28 after second vaccination.

    “In the 5 μg, 10 μg, and 15 μg groups, geometric mean titres of the pseudovirus 50% neutralising antibodies significantly increased by day 15 and peaked at day 28 after the second vaccination, whereas in the 20 μg and 25 μg groups, titres peaked at day 15 then declined slightly at day 28 after second vaccination”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Geometric mean titres were 305 ELISA units in the 5 μg group, 1293 units in the 10 μg group, 529 ELISA units in the 20 μg group, and 726 ELISA units in the 25 μg group 15 days after the second vaccination, which were lower than that in the 15 μg group.

    “Geometric mean titres were 305 ELISA units in the 5 μg vaccine group and 1293 units in the 10 μg vaccine group 15 days after the second vaccination, and 529 ELISA units in the 20 μg vaccine group and 726 ELISA units in the 25 μg vaccine group, which were lower than that in the 15 μg group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    On day 1 after first vaccination, lymphocyte counts increased significantly in the placebo group, which was still within normal clinical range.

    “Additionally, on day 1 after first vaccination, lymphocyte counts increased significantly in the placebo group, which was still within normal clinical range”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    15 days after second vaccination, live SARS-CoV-2 neutralising antibody seroconversion rates were 80% in the 5 μg group, 90% in the 10 μg group, 95% in the 15 μg group, 95% in the 20 μg group, and 94% in the 25 μg group.

    “15 days after second vaccination, seroconversion rates for the live SARS-CoV-2 neutralising antibody were 16 (80%) of 20 in the 5 μg group, 18 (90%) of 20 in the 10 μg group, 19 (95%) of 20 in the 15 μg group, 19 (95%) of 20 in the 20 μg group, and 15 (94%) of 16 in the 25 μg group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After second vaccination, all participants in the 5 μg, 10 μg, 15 μg, and 20 μg groups were positive for IFN-γ-expressing cells and only one participant in the 25 μg group was negative.

    “However, after second vaccination all participants in the 5 μg, 10 μg, 15 μg, and 20 μg groups were positive for IFN-γ-expressing cells and only one participant in the 25 μg group was negative”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    15 days after the second vaccination, RBD-specific IgG antibodies were detected in most participants, with seroconversion rates of 65% in the 5 μg group, 90% in the 10 μg group, 100% in the 15 μg group, 85% in the 20 μg group, and 81% in the 25 μg group.

    “15 days after the second vaccination, RBD-specific IgG antibodies were detected in most participants and the seroconversion rates were 13 (65%) of 20 participants in the 5 μg group, 18 (90%) of 20 in the 10 μg group, 20 (100%) of 20 in the 15 μg group, 17 (85%) of 20 in the 20 μg group, and 13 (81%) of 16 in the 25 μg group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After first immunisation only a few participants developed low titres of neutralising antibodies, whereas after the second immunisation most participants developed high titres of anti-SARS-CoV-2 neutralising antibodies.

    “After first immunisation only a few participants developed low titres of neutralising antibodies, whereas after the second immunisation most participants developed high titres of anti-SARS-CoV-2 neutralising antibodies”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    28 days after the second vaccination, pseudovirus neutralising antibody seroconversion rates were 85% in the 5 μg group, 90% in the 10 μg group, 100% in the 15 μg group, 95% in the 20 μg group, and 88% in the 25 μg group.

    “28 days after the second vaccination, seroconversion rates increased to 17 (85%) of 20 participants in the 5 μg group, 18 (90%) of 20 in the 10 μg group, 20 (100%) of 20 in the 15 μg group, 19 (95%) of 20 in the 20 μg group, and 14 (88%) of 16 in the 25 μg group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The peak titre of neutralising antibodies was detected in the 15 μg group, and geometric mean titres reached 250.9 and 289.7 ELISA units at days 15 and 28 after second vaccination, respectively.

    “The peak titre of neutralising antibodies was detected in the 15 μg group, and geometric mean titres reached 250·9 and 289·7 ELISA units at days 15 and 28 after second vaccination, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The peak IgG antibody titre was observed in the 15 μg group 15 days after the second vaccination and the geometric mean titre was 2414.8 ELISA units.

    “The peak IgG antibody titre was observed in the 15 μg group 15 days after the second vaccination and the geometric mean titre was 2414·8 ELISA units.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Peak titre of neutralising antibodies against live SARS-CoV-2 was detected in the 15 μg group 15 days after second vaccination and the geometric mean titre was about twofold higher than that of a panel of patients recovering from COVID-19.

    “Peak titre of neutralising antibodies against live SARS-CoV-2 was detected in the 15 μg group 15 days after second vaccination and the geometric mean titre was about twofold higher than that of a panel of patients recovering from COVID-19”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most common abnormalities were transient decreases in lymphocyte and neutrophil counts; and increases in C-reactive protein concentrations, urinary tract infections, and albuminuria in vaccine participants.

    “The most common abnormalities were transient decreases in lymphocyte and neutrophil counts; and increases in C-reactive protein concentrations, urinary tract infections, and albuminuria in vaccine participants.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Safety endpoints were assessed in the safety population, which included all participants who received at least one vaccine dose.

    “We assessed the safety endpoints in the safety population, which included all participants who received at least one vaccine dose.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Participants were randomly assigned using block randomisation (5:1) to the ARCoV vaccine or placebo.

    “Participants in each block were randomly assigned (5:1) to the ARCoV vaccine or placebo.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In this phase 1 trial, ARCoV exhibited safety, tolerability, and immunogenicity in healthy Chinese adults.

    “In this phase 1 trial, ARCoV exhibited safety, tolerability, and immunogenicity in healthy Chinese adults.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    An independent data and safety monitoring committee, consisting of an independent statistician, clinician, epidemiologist, and statistical expert, was established before the start of the trial.

    “An independent data and safety monitoring committee, consisting of an independent statistician, clinician, epidemiologist, and statistical expert, was established before the start of the trial.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation.

    “All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    116 participants were eligible for immunogenic assessment.

    “116 participants were eligible for immunogenic assessment.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The randomisation code was assigned to each participant in sequence in order of enrolment.

    “The randomisation code was assigned to each participant in sequence in order of enrolment and then the participants received the investigational products labelled with the same code.”
    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 conductcitation

    The sample size was not determined on the basis of statistical power calculations; the National Medical Products Administration of China recommended a minimum sample size of 20-30 participants for a pilot vaccine trial.

    “The sample size was not determined on the basis of statistical power calculations. The National Medical Products Administration of China recommended a minimum sample size of 20–30 participants for a pilot vaccine trial.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The protocol and informed consent were approved by the Clinical Trial Ethics Committee of Shulan (Hangzhou) hospital (YW2020-031-01).

    “The protocol and informed consent were approved by the Clinical Trial Ethics Committee of Shulan (Hangzhou) hospital (YW2020-031-01).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale.

    “The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale.”
    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

    The trial was done in a dose-escalation manner with sentinels and a 4-day safety observation before proceeding to the next dose group.

    “The trial was done in a dose-escalation manner. The first six participants in each block were sentinels and were randomly assigned (5:1) to receive the vaccine ARCoV or placebo, along with the remaining 18 participants.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The vaccine and placebo were indistinguishable in appearance.

    “The vaccine and placebo were indistinguishable in appearance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    ARCoV demonstrated an acceptable tolerability and safety profile in Chinese adults.

    “In this phase 1 clinical trial, ARCoV, a SARS-CoV-2 mRNA vaccine encoding the RBD of spike protein, demonstrated an acceptable tolerability and safety profile in Chinese adults.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    This study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.

    “This study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Preclinical studies have demonstrated that mRNA-based vaccines can induce potent and broad protective immune responses with an acceptable safety profile.

    “Preclinical studies have demonstrated that mRNA-based vaccines can induce potent and broad protective immune responses with an acceptable safety profile.7”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Maruggi, 2019, mRNA as a transformative technology for vaccine development to control infectious diseases, Mol Tther source

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

    Study design and conductown data

    All participants received the first vaccination and 118 received the second dose.

    “All participants received the first vaccination and 118 received the second dose.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    These findings indicate that the receptor-binding domain-based mRNA vaccine ARCoV has an acceptable safety profile and induces a strong immune response.

    “These findings indicate that the receptor-binding domain-based mRNA vaccine ARCoV has an acceptable safety profile and induces a strong immune response.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Immunogenic endpoints were assessed in the per-protocol population, who completed their assigned two-dose vaccination schedule and with available antibodies results.

    “We assessed immunogenic endpoints in the per-protocol population, who completed their assigned two-dose vaccination schedule and with available antibodies results.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Four participants withdrew, none due to adverse events.

    “Four participants withdrew, none due to adverse events (two withdrew voluntarily after first vaccination, two withdrew after second vaccination; appendix p 15).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Written informed consent was obtained from each participant before enrolment.

    “Written informed consent was obtained from each participant before enrolment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    All 120 participants received at least one dose of the vaccine or placebo and were included in the safety analysis.

    “All 120 participants received at least one dose of the vaccine or placebo and were included in the safety analysis.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    T-helper-1-biased responses might reduce the risk of vaccine-associated antibody-dependent enhancement of virus replication or other adverse reactions.

    “and T-helper-1-biased responses might reduce the risk of vaccine-associated antibody-dependent enhancement of virus replication or other adverse reactions.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Graham, 2020, Rapid COVID-19 vaccine development, Science source

  • May combine two claims.

    Interpretationown data

    ARCoV was immunogenic because participants in all groups had strong humoral and cellular immunity after the second vaccination.

    “ARCoV was immunogenic because participants in all groups had strong humoral and cellular immunity after the second vaccination.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Data interpretation is based on a small sample size.

    “First, data interpretation is based on a small sample size”
    Quote in the paperNot a substantial claim
54 of 54

  • The paper relies on this without support.

    The 34 serum specimens from patients with COVID-19 are representative of convalescent COVID-19 patients for comparing antibody titres.

    “For comparison of the participants' humoral responses with those elicited by SARS-CoV-2 infection, 34 serum specimens from patients with COVID-19 were tested as reference samples (appendix p 7).”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ARCoV is reportedly safe and well-tolerated at 15 μg, and induced high titers of neutralizing antibodies approximately two-fold higher than those of patients who had recovered from COVID-19 infection.

    “ARCoV is reportedly safe and well-tolerated at an amount of 15 μg, which induced high titers of neutralizing antibodies titers (approximately two-fold higher that those of patients which had recovered from COVID-19 infection).439”

    From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [439]

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.

  • Grade 3 fever count exceeds the table's grade 3 systemic count

    Major

    The results report six cases of grade 3 fever in the 25 μg group, while Table 2 reports only five participants with any grade 3 systemic adverse reaction in that group.

  • Grade 3 fever percentage uses the wrong denominator

    Minor

    The stated six cases among 20 participants in the 25 μg group would be 30%, not 38%.

    Reported 38 · recomputed 30

2 of 2

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Chen, G.-L., Li, X.-F., Dai, X.-H., Li, N., Cheng, M.-L., Huang, Z., Shen, J., Ge, Y.-H., Shen, Z.-W., Deng, Y.-Q., Yang, S.-Y., Zhao, H., Zhang, N.-N., Zhang, Y.-F., Wei, L., Wu, K.-Q., Zhu, M.-F., Peng, C.-G., Jiang, Q., Cao, S.-C., Li, Y.-H., Zhao, D.-H., Wu, X.-H., Ni, L., Shen, H.-H., Dong, C., Ying, B., Sheng, G.-P., Qin, C.-F., Gao, H.-N., & Li, L.-J.
Affiliations
  • Academy of Military Medical Sciences (CN)
  • Walvax Biotechnology Co., Ltd. (China) (CN)
  • First Affiliated Hospital Zhejiang University (CN)
  • Zhejiang Shuren University (CN)
  • National Institutes for Food and Drug Control (CN)
  • Beijing Friendship Hospital (CN)
  • Second Affiliated Hospital of Zhejiang University (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Li, Lan-Juan
Venue
The Lancet Microbe
Publisher
Elsevier BV
Published
2022-03
Volume
3
Issue
3
Pages
e193-e202
ISSN
2666-5247 (ISSN-L)
DOI
10.1016/s2666-5247(21)00280-9
PMC
PMC8786321
OpenAlex
W4206966300
Semantic Scholar
192ebe33722c488796791fc1690e05d0fbdf3e53
Cited by
82
References
31
Citations by year
2026: 4 · 2025: 15 · 2024: 21 · 2023: 23 · 2022: 19
FWCI
8.94
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Microbe (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Key Research and Development Program of China Stem Cell and Translational Research
  • Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences
  • National Natural Science Foundation of China
  • National Science Fund for Distinguished Young Scholars
  • Foundation for Innovative Research Groups of the National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Keywords
COVID-19 mRNA vaccine, COVID-19 vaccines, spike protein receptor-binding domain, vaccine safety, immunogenicity, neutralizing antibodies, T cell response, dose escalation, adverse events, healthy adults, Chinese adults, humoral immune response, vaccine safety and immunogenicity
MeSH terms
Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, mRNA Vaccines, Adult, Antibodies, Viral, China, Humans, Immunoglobulin G, Vaccines, Synthetic, Antibodies, Neutralizing, Pandemics, 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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