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Cited by 749SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesViral Infectious Diseases and Gene Expression in Insects

Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2

Open access
Wang, Hui, Zhang, Yuntao, Huang, Baoying, Deng, Wei, Quan, Yaru, Wang, Wenling, Xu, Wenbo, Zhao, Yuxiu +24 more·2020·Cell
DOI 10.1016/j.cell.2020.06.008PMC PMC7275151
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Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 μg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.

AI snapshot

Written from the paper’s full text.

TL;DR

BBIBP-CorV is an inactivated SARS-CoV-2 vaccine candidate that induced neutralizing antibodies across six mammalian species and protected rhesus macaques against intratracheal SARS-CoV-2 challenge. Two-dose immunization with 2 μg/dose provided highly efficient protection without detectable antibody-dependent enhancement of infection.

Key findings

  • The HB02 strain was selected for BBIBP-CorV; it reached peak titers over 7.0 log10 CCID50 at 48–72 hpi in Vero cells, and the P10 stock showed >99.95% whole-genome sequence homology to HB02 with no amino acid variation.
  • BBIBP-CorV induced 100% seroconversion in mice, rats, guinea pigs, rabbits, and nonhuman primates; in rhesus macaques before challenge, geometric mean neutralizing antibody titers were 215 in the 2 μg/dose group and 256 in the 8 μg/dose group.
  • After intratracheal challenge, low-dose macaques had throat viral load peak at 5.33 log10 copies/mL at 5 dpi and fall to 1.12 log10 copies/mL at 7 dpi; all high-dose macaques had negative throat swabs, and no macaque in either vaccinated group had detectable viral load in any lung lobe.
  • Safety studies reported a rat maximum tolerated dose of 24 μg/rat, equivalent to 900 times the human dose, and a no observed adverse effect level of 8 μg/dose in cynomolgus monkeys; no ADE was observed in vaccinated macaques.

Methods

  • Three SARS-CoV-2 strains were isolated from patient bronchoalveolar lavage or throat swabs; HB02 was adapted in Vero cells, produced in a basket reactor, inactivated with β-propiolactone at 1:4,000 at 2°C–8°C, and formulated with aluminum hydroxide adjuvant.
  • Immunogenicity was tested in mice, rats, guinea pigs, rabbits, and cynomolgus monkeys with 2, 4, or 8 μg/dose using one-, two-, or three-dose regimens; neutralizing antibody levels were measured by microtitration CPE assay.
  • Rhesus macaques received two intramuscular immunizations on days 0 and 14 with placebo (n = 2), 2 μg/dose (n = 4), or 8 μg/dose (n = 4), then were intratracheally challenged with 10^6 TCID50 SARS-CoV-2 on day 24; viral loads were measured by RT-PCR in throat and anal swabs and lung lobes, with histopathology at 7 dpi.

Limitations

  • The paper states that protection effects on the upper respiratory tract were not assessed and warrant further evaluation.
  • Evident from the text: this is preclinical animal data only; clinical efficacy and human safety were not yet established, with Phase I in progress and Phase II recently initiated.
  • Evident from the text: nonhuman primate challenge groups were small (n = 2 placebo; n = 4 per vaccinated group) and follow-up after challenge was short (euthanasia at 7 dpi), limiting assessment of durability and late outcomes.

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

Integrity signals

Registry

Crossref · 10.1016/j.cell.2020.06.008

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

6 of 10 cited sources checked · 4 supported · 1 flagged · accuracy not yet measured

  • Interpretationcitation

    Inoculation with BBIBP-CorV does not result in side effects on serum biochemical parameters in rhesus macaques.

    “Because a recent study showed that SARS-CoV-2 infection does not affect host blood chemistry (Munster et al., 2020), this result suggests that inoculation with BBIBP-CorV does not result in side effects on serum biochemical parameters.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Munster et al., 2020 source
  • Findingown data

    All placebo rhesus macaques showed and maintained a high viral load during the whole evaluation period after virus challenge by both throat and anal swabs.

    “All placebo macaques showed and maintained a high viral load during the whole evaluation period after virus challenge by both throat and anal swabs (Figures 3D and 3E; Figures S4B and S4C).”
    Quote in the paperSubstantial claim
  • Findingown data

    In mice, the D0/D21 interval obtained the highest NAb level at 7 days after the second immunization among the two-dose programs.

    “Moreover, use of the D0/D21 interval obtained the highest NAb level at 7 days after the second immunization.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In rhesus macaques, serum biochemical parameters after vaccination and challenge with living virus remained constant.

    “Moreover, the serum biochemical parameters in rhesus macaques after vaccination and challenge with living virus remained constant (Figure S3).”
    Quote in the paperSubstantial claim
  • Findingown data

    In mice, the three-dose (D0/D7/D14) immunization program resulted in higher NAb levels than the one-dose (D0) program in all three dose groups at day 28.

    “The results showed that the three-dose (D0/D7/D14) immunization program resulted in higher NAb levels than the one-dose (D0) program in all three groups at days 28 (Figures 2A and 2C).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 26
  • The quote only partly states this claim. 1

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

    Premisecitation

    Concerns on immunogenicity and safety of DNA vaccines remain.

    “however, the concerns on their immunogenicity and safety still remain (Gary and Weiner, 2020).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Gary and Weiner, 2020 source

      The Introduction (page not available) describes a highly consistent safety record, and the Clinical review of recent DNA vaccines (page not available) says all the constructs it reports were safe and immunogenic in clinical studies. Rather than stating that concerns about both properties still remain, the paper presents recent results as evidence of improved immunogenicity and tolerability. (LLM, conf=0.87)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

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

    Premisecitation

    Neutralizing antibody against the carrier vector virus is still a challenge for adenovirus-vectored vaccines.

    “but the neutralizing antibody against the carrier vector virus is still a challenge (Zhang and Zhou, 2016).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Zhang and Zhou, 2016 source

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

    Premisecitation

    Prior to this study, three candidate vaccines against SARS-CoV-2 were reported: ChAdOx1 nCoV-19, a DNA vaccine, and PiCoVacc.

    “Prior to our reporting of this BBIBP-CorV study, three candidate vaccines against SARS-CoV-2 were reported, including an adenovirus-vectored vaccine (ChAdOx1 nCoV-19), a DNA vaccine, and an inactivated vaccine (PiCoVacc) (Gao et al., 2020, Lurie et al., 2020, van Doremalen et al., 2020, Yu et al., 2020a).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Gao et al., 2020 source
    • cites Lurie et al., 2020 source
    • cites van Doremalen et al., 2020

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

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

    Premisecitation

    The DNA vaccine is easy to produce and stable for storage with limited recovery or residual toxicity.

    “The DNA vaccine is easy to be produced and is stable for storage with limited recovery or residual toxicity”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Gary and Weiner, 2020 source

      The Introduction describes synthetic DNA vaccines as rapidly synthesized and scalable, and says the platform addresses goals of temperature stability and consistent manufacture. It also reports a consistent safety record, but does not establish the more specific claim of limited recovery or residual toxicity. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    The recombinant adenovirus-vectored vaccine is easily manipulated for genetic modification and capable of inducing potent antigen-specific immune responses.

    “The recombinant adenovirus-vectored vaccine is easily manipulated for genetic modification and capable of inducing potent antigen-specific immune responses”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Zhang and Zhou, 2016 source

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

    Findingnone given

    BBIBP-CorV exhibits efficient productivity for vaccine manufacture.

    “In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At 7 dpi, no macaques in the low-dose and high-dose groups had a detectable viral load in any lung lobe, which was significantly different from the placebo group.

    “No macaques in the low-dose and high-dose groups had a detectable viral load in any lung lobe, which was significantly different from the results in the placebo group (Figure 3F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In mice, one-dose immunization with 2, 4, or 8 μg/dose of BBIBP-CorV resulted in 100% seroconversion at 7 days after immunization, and the immunization effect was time dependent.

    “The results showed that the seroconversion rate in the high-, middle-, and low-dose groups reached 100% at 7 days after immunization, and the immunization effect was time dependent (Figure 2 A; Table S1).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Only 3 of 7 sections of the lung lobes were detected to have infection in the placebo group.

    “To note, only 3 of 7 sections of the lung lobes were detected to have infection in the placebo group, possibly because the virus infection in the lung lobes is dynamically changing.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The P7 stock virus replicated efficiently and reached a peak titer over 7.0 log10 CCID50 by 48-72 h post-infection at MOI 0.01-0.3 in Vero cells.

    “Growth kinetic analysis of the P7 stock in Vero cells showed that the stock virus could replicate efficiently and reached a peak titer over 7.0 log10 CCID50 by 48–72 h post-infection (hpi) at multiplicities of infection (MOI) of 0.01–0.3 (Figure 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At 7 dpi, placebo-treated macaques produced low-level NAb with a titer of 1:16, whereas vaccinated macaques had NAb levels highest at 1:2,048 (average 1:860) in the high-dose group and 1:1,024 in the low-dose group (average 1:512).

    “At 7 dpi, the macaques treated with placebo produced low-level NAb with a titer of 1:16, whereas the NAb levels of the vaccinated macaques were highest at 1:2,048 (average 1:860) in the high-dose group and 1:1,024 in the low-dose group (average 1:512) (Figure 3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the placebo group, a high viral load was detected in the left lower lung, right lower lung, and right accessory lung, and pathological histology showed severe interstitial pneumonia.

    “In the placebo group, a high viral load was detected in the left lower lung, right lower lung, and right accessory lung, and the pathological histology analysis results showed severe interstitial pneumonia.”
    Quote in the paperSubstantial claim

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

    Findingown data

    The vaccine particles are oval with spikes and diameters of approximately 100 nm.

    “A negatively stained electron microscopy image visualized oval viral particles with spikes with the diameters of approximately 100 nm (Figure 1F).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In rats, there was no significant difference in weight or feeding state between the BBIBP-CorV and control groups.

    “Moreover, there was no significant difference in weight or feeding state between the experimental groups and control groups (Figure 4 A; Figure S4D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the low-dose (2 μg/dose) rhesus macaque group, viral load in throat swabs peaked at 5.33 log10 copies/mL at 5 dpi and decreased to 1.12 log10 copies/mL at 7 dpi, significantly lower than that of the placebo group.

    “In contrast, the viral load in the throat swabs of the low-dose group peaked (5.33 log10copies/mL) at 5 dpi and then decreased to 1.12 log10copies/mL at 7 dpi, which was significantly lower than that of the placebo group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both low-dose and high-dose BBIBP-CorV conferred highly efficient protection against SARS-CoV-2 in macaques without observed antibody-dependent enhancement of infection.

    “Taken together, all these results demonstrated that both low-dose and high-dose BBIBP-CorV conferred highly efficient protection against SARS-CoV-2 in macaques without observed antibody-dependent enhancement of infection.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The rhesus macaque intratracheal challenge model with 10^6 TCID50 SARS-CoV-2 reproduces human COVID-19 disease sufficiently to assess vaccine protection.
    • Rests on an assumption: Absence of detectable antibody-dependent enhancement in rhesus macaques indicates absence of ADE in humans.

  • May combine two claims.

    Findingown data

    The HB02 strain showed the most optimal replication and generated the highest virus yields in Vero cells among the three viral strains.

    “We first found that the HB02 strain showed the most optimal replication and generated highest virus yields in Vero cells among three viral strains (Figure 1 A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In mice, NAb levels at 7, 14, and 21 days in the low- and middle-dose groups show significant variation, whereas no significant variation between 21 and 28 days was observed.

    “The NAb levels at 7, 14, and 21 days in the low- and middle-dose groups show significant variation, whereas no significant variation between 21 and 28 days was observed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Inactivation of three batches of virus with β-propionolactone eliminated viral infectivity, validating good stability and repeatability of the inactivation process.

    “The inactivation of three batches of virus eliminated viral infectivity, validating the good stability, and repeatability of the inactivation process (Figure 1D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In cynomolgus monkeys, granulomatous inflammation was observed in the 2, 4, and 8 μg/dose groups on D25 and remained at the end of the recovery period (D36), with a slight improvement compared to that observed on D25.

    “Granulomatous inflammation was observed in the 2, 4, and 8 μg/dose groups on D25 and remained at the end of the recovery period (D36), with a slight improvement compared to that observed on D25.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In guinea pigs, the low- and high-dose groups showed no allergic reactions at D19 and D26, and the allergic reactions were negative.

    “In sharp contrast, in the low- and high-dose groups, no allergic reactions at D19 and D26 were found, and the allergic reactions were negative.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In cynomolgus monkeys, the animals showed only local irritation characterized by mild to severe granulomatous inflammation due to injection, but this reaction was absent at 2 weeks after injection.

    “The animals showed only local irritation characterized by mild to severe granulomatous inflammation due to injection, but this reaction was absent at 2 weeks after injection.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The no observed adverse effect level was found to be 8 μg/dose in the cynomolgus monkey trial.

    “The no observed adverse effect level was found to be 8 μg/dose in this trial.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    BBIBP-CorV conferred effective protection and prevented all vaccinated macaques from viral interstitial pneumonia.

    “both BBIBP-CorV and ChAdOx1 nCoV-19 conferred effective protection and prevented all vaccinated macaques from viral interstitial pneumonia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    BBIBP-CorV vaccination could efficiently block the infection of SARS-CoV-2 and COVID-19 disease in monkeys.

    “demonstrating the BBIBP-CorV vaccination could efficiently block the infection of SARS-CoV-2 and COVID-19 disease in monkey.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The rhesus macaque intratracheal challenge model with 10^6 TCID50 SARS-CoV-2 reproduces human COVID-19 disease sufficiently to assess vaccine protection.

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

    Interpretationown data

    The results support further evaluation of BBIBP-CorV in a clinical trial.

    “These results support the further evaluation of BBIBP-CorV in a clinical trial.”
    • Also stated in: § Introduction · plain
      “Here, we report the study of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) and show that its potency and safety in preclinical studies warrants further clinical evaluation.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The immunogenicity and protective efficacy observed in animal models predict immunogenicity and protection in humans.

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

    Study design and conductnone given

    Rhesus macaque studies were performed in an ABSL-3 laboratory and approved by IACUC of the Institute of Laboratory Animal Science, CAMS with approval number GH20008.

    “Rhesus macaque studies were performed in an animal biosafety level 3 (ABSL-3) laboratory and approved by the IACUC of the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences with approval number GH20008.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The sample size and statistical method were indicated in Method Details or Figure Legends.

    “The sample size and statistical method were indicated in Method Details or Figure Legends.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The pipeline used for BBIBP-CorV pilot-scale production sheds light on rapid vaccine development against other coronaviruses.

    “and the pipeline used for BBIBP-CorV pilot-scale production also sheds light on rapid vaccine developing against other coronavirus.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All cynomolgus monkey experiments were approved by the institutional animal ethics committee (IACUC) prior to operation.

    “All cynomolgus monkey experiments were approved by the institutional animal ethics committee (IACUC) prior to operation.”
    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

    All experiments were randomized and no data was excluded from data analysis.

    “All experiments were randomized and no data was excluded from data analysis.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All experiments in this study were performed with replication numbers indicated in Method Details or Figure Legends.

    “All experiments in this study were performed with replications numbers indicated in Method Details or Figure Legends.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All animals participating in this research are in good health and are not involved in other experimental procedures.

    “All animals participate in this research are in good health and are not involved in other experimental procedure.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All animals involved in this study were housed and cared for in an AAALAC-accredited facility.

    “All animals involved in this study were housed and cared for in an Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited facility.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Cynomolgus monkeys, rabbits, guinea pigs, rats and mice were randomly divided into three groups.

    “Cynomolgus monkeys, rabbits, guinea pigs, rats and mice were randomly divided into three groups”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Protection effects on the upper respiratory tract are not assessed in this study and warrant further evaluation.

    “Of note, the protection effects on the upper respiratory tract are not assessed in this study and warrant further evaluation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    ChAdOx1 nCoV-19 conferred effective protection and prevented all vaccinated macaques from viral interstitial pneumonia.

    “both BBIBP-CorV and ChAdOx1 nCoV-19 conferred effective protection and prevented all vaccinated macaques from viral interstitial pneumonia.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites van Doremalen et al., 2020

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

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

    Premisecitation

    For ChAdOx1 nCoV-19, 5 of 6 lung lobes in the vaccinated group showed detectable viral load.

    “For ChAdOx1 nCoV-19, 5 of 6 lung lobes in vaccinated group showed the detectable viral load (van Doremalen et al., 2020)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites van Doremalen et al., 2020

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

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

    Study design and conductnone given

    All experimental procedures with mice, rats, rabbits, guinea pigs, and nonhuman primates were conducted according to Chinese animal use guidelines and were approved by IACUC.

    “All experimental procedures with mice, rats, rabbits, guinea pigs, and nonhuman primates were conducted according to Chinese animal use guidelines and were approved by the Institutional Animal Care and Use Committee (IACUC).”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    In protection studies, ChAdOx1 nCoV-19 and the DNA vaccine were challenged by both lower and upper respiratory tract, whereas PiCoVacc and BBIBP-CorV were intratracheally challenged.

    “In the protection studies, ChAdOx1 nCoV-19 and the DNA vaccine were challenged by both lower and upper respiratory tract, whereas PiCoVacc and BBIBP-CorV were intratracheally challenged.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationown data

    Two-dose low-dose BBIBP-CorV might benefit further clinical usage of the inactivated vaccine with less adverse effects.

    “which might benefit the further clinical usage of the inactivated vaccine with less adverse effects.”
    Quote in the paperSubstantial claim
41 of 41

  • The paper relies on this without support.

    The immunogenicity and protective efficacy observed in animal models predict immunogenicity and protection in humans.

    “These results support the further evaluation of BBIBP-CorV in a clinical trial.”
    “indicating the potential good safety of BBIBP-CorV in humans.”

  • The paper relies on this without support.

    The rhesus macaque intratracheal challenge model with 10^6 TCID50 SARS-CoV-2 reproduces human COVID-19 disease sufficiently to assess vaccine protection.

    “At D24 (10 days after the second immunization), all macaques were intratracheally challenged with l06 TCID50 of SARS-CoV-2 per monkey under anesthesia.”
    “demonstrating the BBIBP-CorV vaccination could efficiently block the infection of SARS-CoV-2 and COVID-19 disease in monkey.”

  • The paper relies on this without support.

    Absence of detectable antibody-dependent enhancement in rhesus macaques indicates absence of ADE in humans.

    “without detectable antibody-dependent enhancement of infection.”
    “without observed antibody-dependent enhancement of infection.”

  • The paper relies on this without support.

    The Vero cells used for virus isolation and vaccine production are certified by WHO for vaccine production.

    “Notably, all of these strains were isolated from Vero cells, which have been certified by WHO for vaccine production.”

  • The paper relies on this without support.

    No effective antiviral drug against SARS-CoV-2 exists.

    “In the absence of an effective antiviral drug against SARS-CoV-2, vaccines with good potency and safety will be needed to effectively establish immunity in population.”
5 of 5

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?

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.

  • Local inflammation is both present and absent at two weeks

    Major

    Granulomatous inflammation is said to remain on day 36, which is two weeks after the final injection on day 22. The next sentence says that this injection-site reaction was absent two weeks after injection.

  • Day 25 is misidentified as three days after the third vaccination

    Minor

    The stated vaccination days make day 25 three days after the fourth vaccination on day 22, not the third vaccination on day 15.

2 of 2

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Related

Authors
Wang, H., Zhang, Y., Huang, B., Deng, W., Quan, Y., Wang, W., Xu, W., Zhao, Y., Li, N., Zhang, J., Liang, H., Bao, L., Xu, Y., Ding, L., Zhou, W., Gao, H., Liu, J., Niu, P., Zhao, L., Zhen, W., Fu, H., Yu, S., Zhang, Z., Xu, G., Li, C., Lou, Z., Xu, M., Qin, C., Wu, G., Gao, G. F., Tan, W., & Yang, X.
Affiliations
  • National Vaccine and Serum Institute (CN)
  • Chinese Center For Disease Control and Prevention (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • National Institutes for Food and Drug Control (CN)
  • Tsinghua University (CN)
  • China National Pharmaceutical Group Corporation (China) (CN)
Corresponding author
  • Li, Changgui
  • Lou, Zhiyong
  • Xu, Miao
  • Qin, Chuan
  • Wu, Guizhen
  • Gao, George Fu
  • Tan, Wenjie
  • Yang, Xiaoming
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2020-08
Volume
182
Issue
3
Pages
713-721.e9
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2020.06.008
PMC
PMC7275151
OpenAlex
W3034173374
Semantic Scholar
6f16ad05c488ce92ac0c56e4f8b5a81cb7c39d0d
Cited by
748
References
26
Citations by year
2026: 12 · 2025: 37 · 2024: 55 · 2023: 83 · 2022: 212 · 2021: 270 · 2020: 78 · 2018: 1
FWCI
21.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • Beijing Science and Technology Planning Project
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
Keywords
BBIBP-CorV, inactivated vaccine, SARS-CoV-2, COVID-19 vaccines, neutralizing antibodies, vaccine production, genetic stability, antibody-dependent enhancement, rhesus monkeys, Macaca fascicularis, intratracheal challenge, vaccine safety
MeSH terms
Immunogenicity, Vaccine, Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Antibodies, Viral, Chlorocebus aethiops, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Guinea Pigs, Macaca fascicularis, Macaca mulatta, Male, Mice, Inbred BALB C, Phylogeny, Pneumonia, Viral, Rabbits, Vero Cells, Viral Vaccines, Vaccines, Inactivated, Rats, Wistar, Coronavirus Infections, Mice, Rats, Antibodies, Neutralizing, Pandemics

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 2026-10-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-28.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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