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Cited by 1,438SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesSARS-CoV-2 detection and testing

Development of an inactivated vaccine candidate for SARS-CoV-2

Open access
Gao, Qiang, Bao, Linlin, Mao, Haiyan, Wang, Lin, Xu, Kangwei, Yang, Minnan, Li, Yajing, Zhu, Ling +26 more·2020·Science
DOI 10.1126/science.abc1932PMC PMC7202686

Published version of a preprint

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Abstract

Vaccine candidate tested in monkeys: Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an urgent race to develop a vaccine. Gao et al. report preclinical results of an early vaccine candidate called PiCoVacc, which protected rhesus macaque monkeys against SARS-CoV-2 infection when analyzed in short-term studies. The researchers obtained multiple SARS-CoV-2 strains from 11 hospitalized patients across the world and then chemically inactivated the harmful properties of the virus. Animals were immunized with one of two vaccine doses and then inoculated with SARS-CoV-2. Those that received the lowest dose showed signs of controlling the infection, and those receiving the highest dose appeared more protected and did not have detectable viral loads in the pharynx or lungs at 7 days after infection. The next steps will be testing for safety and efficacy in humans. Science , this issue p. 77

AI snapshot

Written from the paper’s full text.

TL;DR

PiCoVacc, a purified inactivated SARS-CoV-2 vaccine candidate, induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and macaques and protected macaques against SARS-CoV-2 challenge without observable antibody-dependent enhancement. High-dose immunization (6 μg per dose) provided complete protection in macaques, whereas medium-dose (3 μg per dose) provided partial protection.

Key findings

  • In mice, PiCoVacc elicited S- and RBD-specific IgG that peaked at titers of 819,200 and 409,600, respectively, at week 6; N-specific IgG was ~30-fold lower. Neutralizing antibody titers reached ~1,500 for low/medium doses and ~3,000 for high dose at week 7. In rats, maximum neutralizing titers reached 2,048–4,096 at week 7.
  • PiCoVacc-elicited antibodies neutralized 10 representative SARS-CoV-2 strains in mice and rats, suggesting broader neutralizing activity against circulating strains.
  • In rhesus macaques immunized three times with 3 μg or 6 μg per dose, S-specific IgG and neutralizing antibodies rose to ~12,800 and ~50, respectively, by week 3 before challenge. After intratracheal challenge with 10^6 TCID50 of SARS-CoV-2 CN1, all four high-dose macaques had no detectable viral loads in pharynx, crissum, and lung at day 7; medium-dose macaques showed partial protection with viral blips in pharyngeal (3/4), anal (2/4), and pulmonary (1/4) specimens and ~95% viral load reduction versus sham.
  • Control macaques showed excessive viral genomic RNA copies (10^4–10^6/ml) in pharynx, crissum, and lung by day 3–7 post-inoculation and severe interstitial pneumonia. No fever, weight loss, notable hematological/biochemical/cytokine changes, or histopathological pathology were observed in vaccinated macaques, and no ADE was observed.

Methods

  • SARS-CoV-2 strains were isolated from bronchoalveolar lavage fluid of 11 hospitalized patients; strain CN2 was selected for PiCoVacc, plaque-purified and passaged in Vero cells, propagated in a 50-liter Vero cell culture, inactivated with β-propiolactone, and purified by depth filtration and two chromatography steps.
  • Immunogenicity was assessed in BALB/c mice (n=10), Wistar rats (n=10), and rhesus macaques. Macaques received three intramuscular immunizations at day 0, 7, and 14 with medium (3 μg) or high (6 μg) doses (n=4 per group) for immunogenicity/challenge, or low (1.5 μg) or high (6 μg) doses versus sham/placebo (n=10 per group) for safety.
  • Main analyses included ELISAs for S-, RBD-, and N-specific IgG, microneutralization assays against 10 SARS-CoV-2 strains, qRT-PCR for viral loads, histopathology, hematology, lymphocyte subsets, and cytokine measurements.

Limitations

  • The paper states that the possibility of ADE after antibody titers wane could not be ruled out, and that longer post-vaccination observation of challenged animals is warranted. It also states it is still too early to define the best animal model for studying SARS-CoV-2 infection.
  • Evident from the text: this is preclinical animal data only, with no human safety or efficacy results; macaque immunogenicity/challenge groups were small (n=4), and one medium-dose animal had a ~10-fold higher neutralizing titer that skewed group comparisons.
  • Evident from the text: the medium dose provided only partial protection, with detectable viral blips in some specimens at day 7 after infection.

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

Integrity signals

Registry

Crossref · 10.1126/science.abc1932

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

11 of 13 cited sources checked · 2 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    The cytokine storm induced by excessive T-cell responses has been shown to accentuate the pathogenesis of COVID-19.

    “The “cytokine storm” induced by excessive T-cell responses have been actually shown to accentuate the pathogenesis of COVID19 (18, 19).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [18] 18. Nicholls J. M., Poon L. L. M., Lee K. C., Ng W. F., Lai S. T., Leung C. Y., Chu C. M., Hui P. K., Mak K. L., Lim W., Yan K. W., Chan K. H., Tsang N. C., Guan Y., Yuen K. Y., Peiris J. S., Lung pathology of fatal severe acute respiratory syndrome. Lancet 361, 1773–1778 (2003). 10.1016/S0140-6736(03)13413-7 source

      The Discussion (page unavailable) suggests that cytokines released by stimulated macrophages contribute to the pathogenesis of SARS. It does not show that excessive T-cell responses induce a cytokine storm or that this mechanism accentuates COVID-19 pathogenesis; it also presents the SARS mechanism as a suggestion rather than an established finding. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [19] 19. Zheng H. Y., Zhang M., Yang C. X., Zhang N., Wang X. C., Yang X. P., Dong X. Q., Zheng Y. T., Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell. Mol. Immunol. 17, 541–543 (2020). 10.1038/s41423-020-0401-3 source

      In the paper’s main text (page unavailable), the proposed direction is the reverse: virus-induced inflammatory storms can cause systemic T-cell responses. The authors also report no significant differences in the inflammatory cytokines they measured, so this paper does not show that excessive T-cell responses induce a cytokine storm that worsens COVID-19. (LLM, conf=0.87)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Findingown data

    The serological profile of PiCoVacc-immunized mice closely matches that of recovered COVID-19 patients.

    “which closely matches the serological profile of the blood of recovered COVID-19 patients (Fig. 2, A and B) (11).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] 11. L. Liu, S. Wang, S. Zheng, A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients. MedRxiv 2020.03.06.20031856 [Preprint]. 8 March 2020;. 10.1101/2020.03.06.20031856 source

      The Performance and validation section (p. 10) reports SARS-CoV-2 IgM and IgG results in admitted patients, providing evidence about human antibody responses. It does not identify those patients as recovered or compare their serological profile with PiCoVacc-immunized mice. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    Protection from subsequent coronavirus infections is largely mediated by humoral immunity.

    “protection from subsequent coronavirus infections is largely mediated by humoral immunity (16, 17).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [16] 16. Prompetchara E., Ketloy C., Palaga T., Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac. J. Allergy Immunol. 38, 1–9 (2020). source

      The 'Adaptive Immune Responses' section says that humoral immunity, especially neutralizing antibodies, helps prevent future reinfection. It does not say that protection is largely mediated by humoral immunity; the same section describes Th1 responses as dominant in adaptive antiviral immunity. Page numbers are unavailable in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [17] 17. Zhao J., Perera R. A. P. M., Kayali G., Meyerholz D., Perlman S., Peiris M., Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection. J. Virol. 89, 6117–6120 (2015). 10.1128/JVI.00446-15 source

      In the ‘Protective efficacy in MERS-CoV-infected mice’ results (page not specified in the indexed passage), transferred dromedary serum helped clear MERS-CoV, and protection tracked neutralizing-antibody titer. This supports a protective role for antibodies in that mouse model, but does not establish that humoral immunity largely mediates protection from subsequent coronavirus infections generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Previous reports on SARS and MERS vaccine candidates raised concerns about pulmonary immunopathology caused by Th2 response or ADE.

    “Previous reports on the development of SARS and MERS vaccine candidates raised concerns about pulmonary immunopathology, either directly caused by a type 2 helper T-cell (Th2) response or as a result of ADE (4, 14, 15).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [4] 4. Lurie N., Saville M., Hatchett R., Halton J., Developing Covid-19 vaccines at pandemic speed. N. Engl. J. Med. 10.1056/NEJMp2005630 (2020). 10.1056/NEJMp2005630 source
    • cites [14] 14. Tseng C. T., Sbrana E., Iwata-Yoshikawa N., Newman P. C., Garron T., Atmar R. L., Peters C. J., Couch R. B., Correction: Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLOS ONE 7, e35421 (2012). 10.1371/annotation/2965cfae-b77d-4014-8b7b-236e01a35492 source

      The Discussion (page unavailable) reports Th2-type lung immunopathology after vaccinated animals were challenged with SARS-CoV, supporting the concern about SARS vaccine candidates. It discusses antibody-mediated disease enhancement in a feline coronavirus infection, but does not establish ADE as the cause of pulmonary immunopathology from SARS vaccines; it does not address MERS vaccine candidates. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [15] 15. Yong C. Y., Ong H. K., Yeap S. K., Ho K. L., Tan W. S., Recent advances in the vaccine development against Middle East respiratory syndrome-coronavirus. Front. Microbiol. 10, 1781 (2019). 10.3389/fmicb.2019.01781 source

      The ‘Potential Antibody Dependent Enhancement (ADE) of Mers-CoV Infection’ section describes ADE as a vaccine-safety concern, reports adverse inflammatory responses in animals given SARS vaccine candidates, and says no ADE had been observed for MERS-CoV. The ‘Criteria for an Effective Mers-CoV Vaccine’ section reports Th2-biased responses to a MERS vaccine formulation, but does not link Th2 responses or ADE to pulmonary immunopathology. The specific lung-pathology mechanism in the claim is therefore not supported by this copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Premisecitation

    Antibodies targeting N of SARS-CoV-2 do not provide protective immunity against infection.

    “the antibodies targeting N of SARS-CoV-2 do not provide protective immunity against the infection (12)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] 12. Gralinski L. E., Menachery V. D., Return of the coronavirus: 2019-nCoV. Viruses 12, E135 (2020). 10.3390/v12020135 source
  • Classified as probably not a substantial claim. 3
  • May combine two claims. 17

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

    Premisecitation

    Purified inactivated viruses have been traditionally used for vaccine development and have been found safe and effective for preventing diseases caused by influenza virus and poliovirus.

    “Purified inactivated viruses have been traditionally used for vaccine development and such vaccines have been found to be safe and effective for the prevention of diseases caused by viruses like influenza virus and poliovirus (7, 8).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [7] 7. Murdin A. D., Barreto L., Plotkin S., Inactivated poliovirus vaccine: Past and present experience. Vaccine 14, 735–746 (1996). 10.1016/0264-410X(95)00211-I source
    • cites [8] 8. Vellozzi C., Burwen D. R., Dobardzic A., Ball R., Walton K., Haber P., Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring. Vaccine 27, 2114–2120 (2009). 10.1016/j.vaccine.2009.01.125 source

      The Background describes influenza vaccines as the primary method for controlling influenza and reports reassuring trial safety findings for trivalent inactivated influenza vaccine. The Discussion says the vaccines reviewed included purified subunit formulations. The paper does not address poliovirus vaccines, and its safety surveillance does not establish effectiveness for every purified inactivated vaccine. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Previous studies have shown that N-specific IgG is largely abundant in serum of COVID-19 patients and serves as a clinical diagnostic marker.

    “previous studies have shown that the N-specific IgG is largely abundant in the serum of COVID-19 patients and serves as one of the clinical diagnostic markers (11).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] 11. L. Liu, S. Wang, S. Zheng, A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients. MedRxiv 2020.03.06.20031856 [Preprint]. 8 March 2020;. 10.1101/2020.03.06.20031856 source

      The Performance and validation section (p. 10) reports that an N-protein-based assay detected IgM and/or IgG in 81.5% of the 238 patients, supporting the use of these antibodies as diagnostic markers. It does not establish that N-specific IgG alone was abundant in most patients; the Discussion (p. 13) also says antibody detection depends on disease stage. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    In macaques immunized with 3 or 6 μg PiCoVacc, S-specific IgG and NAb were induced at week 2 and rose to ~12,800 and ~50, respectively, at week 3 before virus challenge in both vaccinated groups.

    “S-specific IgG and NAb were induced at week 2 and rose to ~12,800 and ~50, respectively at week 3 (before virus challenge) in both vaccinated groups”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All control (sham and placebo) macaques showed excessive copies (10^4-10^6/ml) of viral genomic RNA in pharynx, crissum and lung by day 3-7 post-inoculation and severe interstitial pneumonia.

    “all control (sham and placebo) macaques showed excessive copies (104-106/ml) of viral genomic RNA in the pharynx, crissum and lung by day 3-7 post-inoculation (dpi) and severe interstitial pneumonia (Fig. 3, C to F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SARS-CoV-2 S- and RBD-specific IgG developed quickly in vaccinated mice and peaked at titers of 819,200 and 409,600, respectively, at week 6.

    “SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated mice and peaked at the titer of 819,200 (>200 μg/ml) and 409,600 (>100 μg/ml), respectively, at week 6 (Fig. 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The P5 stock of PiCoVacc (CN2) replicated efficiently in Vero cells and reached a peak titer of 6-7 log10 TCID50/ml by 3 or 4 days post infection at MOI 0.0001-0.01 at 33°C-37°C.

    “Growth kinetics analysis of the P5 stock in Vero cells showed that this stock replicated efficiently and reached a peak titer of 6-7 log10 TCID50/ml by 3 or 4 days post infection (dpi) at multiplicities of infection (MOI) of 0.0001-0.01 at temperatures between 33°C-37°C (Fig. 1B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SARS-CoV-2 strains isolated from BALF of 11 hospitalized patients are widely scattered on the phylogenetic tree and represent circulating SARS-CoV-2 populations to some extent.

    “The 11 samples contained SARS-CoV-2 strains that are widely scattered on the phylogenic tree constructed from all available sequences, representing, to some extent, circulating SARS-CoV-2 populations (Fig. 1A and fig. S1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Viral loads decreased significantly in all vaccinated macaques but increased slightly in control animals from day 3-7 after infection.

    “Viral loads decreased significantly in all vaccinated macaques, but increased slightly in control animals from day 3-7 after infection (Fig. 3, C to E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the medium dose immunized group, viral blip was partially detected from pharyngeal (3/4), anal (2/4) and pulmonary (1/4) specimens at day 7 after infection, while viral loads showed ~95% reduction compared to sham groups.

    “In the medium dose immunized group, we indeed partially detected the viral blip from pharyngeal (3/4), anal (2/4) and pulmonary (1/4) specimens at day 7 after infection, while viral loads presented a ~95% reduction when compared to the sham groups (Fig. 3, C to E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cryo-EM analysis showed intact oval-shaped PiCoVacc particles with diameters of 90-150 nm, embellished with crown-like spikes, representing a prefusion state.

    “cryo-electron microscopy (cryo-EM) analysis showed intact oval-shaped particles with diameters of 90-150 nm, which are embellished with crown-like spikes, representing a prefusion state of the virus (Fig. 1E).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neither fever nor weight loss was observed in any macaque after PiCoVacc immunization, and appetite and mental state remained normal.

    “Neither fever nor weight loss was observed in any macaque after the immunization of PiCoVacc, and the appetite and mental state of all animals remained normal (fig. S3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All vaccinated macaques were largely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung.

    “all vaccinated macaques were largely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    NAb titer in vaccinated macaque groups decreased by ~30% by 3 days post infection, then rapidly increased from day 5-7 after infection.

    “NAb titer in vaccinated groups decreased by ~30% by 3 days post infection to neutralize viruses, then rapidly increased from day 5-7 after infection to maintain neutralization efficacy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neutralizing antibody titer against CN1 emerged at week 1 (12 for high dose), surged after week 2 booster, and reached ~1,500 for low and medium doses and 3,000 for high dose at week 7 in mice.

    “the neutralizing antibody titer against the CN1 strain emerged at week 1 (12 for high dose immunization), surged after the week 2 booster and reached up to around 1,500 for low and medium doses, and 3,000 for the high dose at week 7, respectively (Fig. 2A).”
    Quote in the paperSubstantial claim

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

    Interpretationown data

    The higher NAb titer in the medium dose group at week 3 may be due to individual differences in the ability of one animal to elicit ~10-fold higher titer.

    “possibly due to individual differences in the ability of one animal in the medium dose group in eliciting ~10-fold higher titer when compared to the other three animals (Fig. 3B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    PiCoVacc CN2 strain possesses excellent genetic stability without S mutations that might potentially alter NAb epitopes.

    “suggesting that PiCoVacc CN2 strain possesses excellent genetic stability without the S mutations that might potentially alter the NAb epitopes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The very mild and focal histopathological changes in vaccinated macaques were probably caused by direct inoculation of 10^6 TCID50 virus into the lung through intratracheal route, needing longer than one week to recover completely.

    “which probably were caused by a direct inoculation of 106 TCID50 of virus into the lung through intratracheal route, that needed longer time (more than one week) to recover completely (Fig. 3F).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The intratracheal challenge with 10^6 TCID50 SARS-CoV-2 CN1 in macaques models natural human SARS-CoV-2 infection sufficiently for evaluating vaccine protection.

  • May combine two claims.

    Interpretationreasoning

    Higher NAb titers in the medium dose vaccinated group at day 7 after infection (~400) compared to high dose (~145) might have resulted from relatively low levels of viral replication, suggesting a requirement of longer time for complete viral clearance.

    “higher NAb titers observed in the medium dose vaccinated group at day 7 after infection (~400 for 4 macaques) might have resulted from relatively low levels of viral replication, suggesting a requirement of longer time for complete viral clearance.”
    Quote in the paperNot a substantial claim
18 of 18

  • The paper relies on this without support.

    There is an urgent need for a SARS-CoV-2 vaccine because no specific antiviral drugs or vaccines are available.

    “No specific antiviral drugs or vaccines against the newly emerged SARS-CoV-2 are currently available. Therefore, urgency in the development of vaccines is of vital importance to curb the pandemic and prevent new viral outbreaks.”

  • The paper relies on this without support.

    Protection against SARS-CoV-2 challenge in rhesus macaques predicts protective efficacy in humans.

    “These data support clinical development of SARS-CoV-2 vaccines for humans.”
    “Collectively these results suggest a path forward for clinical development of SARS-CoV-2 vaccines for use in humans.”

  • The paper relies on this without support.

    Neutralizing antibody titers are a valid correlate of protection against SARS-CoV-2 in humans.

    “These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains.”
    “S-specific IgG and NAb were induced at week 2 and rose to ~12,800 and ~50, respectively at week 3 (before virus challenge) in both vaccinated groups”

  • The paper relies on this without support.

    The absence of observable ADE in macaques during the study period predicts absence of ADE in humans.

    “without observable antibody-dependent enhancement of infection.”
    “No antibody-dependent enhancement (ADE) of infection was observed for the vaccinated macaques despite the observation that relatively low NAb titer existed within the medium dose group before infection, offering partial protection.”

  • The paper relies on this without support.

    The intratracheal challenge with 10^6 TCID50 SARS-CoV-2 CN1 in macaques models natural human SARS-CoV-2 infection sufficiently for evaluating vaccine protection.

    “we conducted a challenge study by a direct inoculation of 106 TCID50 of SARS-CoV-2 CN1 into the animal lung through the intratracheal route at day 22 (one week after the third immunization) in vaccinated and control macaques to verify the protective efficacy.”
    “which probably were caused by a direct inoculation of 106 TCID50 of virus into the lung through intratracheal route, that needed longer time (more than one week) to recover completely (Fig. 3F).”
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?

  • Two or three doses of inactivated SARS-CoV-2 virus vaccine could induce neutralizing antibodies at levels of ∼1/50, which provides full protection against SARS-CoV-2 in rhesus macaques.

    “It has been reported that two or three doses of inactivated SARS-CoV-2 virus vaccine could induce neutralizing antibodies at levels of ∼1/50, which provides full protection against SARS-CoV-2 in rhesus macaques (Gao et al., 2020).”

    From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Gao et al., 2020

    The macaque challenge results report neutralizing-antibody titers of about 50 after three doses, but do not establish protection after two doses. The Abstract distinguishes partial protection at the 3 μg dose from complete protection at the 6 μg dose; it does not show that a titer of about 50 itself provides full protection. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • Protective immunity can be expected in most macaques immunized with two doses of ARCoV.

    “protective immunity can be expected in most macaques immunized with two doses of ARCoV.”

    From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Gao et al., 2020

    The paper’s account of the macaque challenge study (Abstract; Fig. 3) reports that vaccinated animals were largely protected. But it tested PiCoVacc given three times, not ARCoV given twice, so it does not support the claimed vaccine or dosing schedule. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Gao and colleagues showed that, in mice, rats, and rhesus monkeys, 6 μg CoronaVac induced SARS-CoV-2-specific neutralising antibodies that effectively neutralised ten representative SARS-CoV-2 strains and provided complete protection against SARS-CoV-2 challenge in non-human primates.

    “Gao and colleagues13 showed that, in mice, rats, and rhesus monkeys, 6 μg CoronaVac induced SARS-CoV-2-specific neutralising antibodies that effectively neutralised ten representative SARS-CoV-2 strains and provided complete protection against SARS-CoV-2 challenge in non-human primates.”

    From Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey (2021) · cites this paper as [13]

    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

  • In rhesus macaques, IC50 titers as low as 1:8 were associated with protection from re-infection, and IC50 titers as low as 1:50 were associated with reduced viral load and protection from lung pathology.

    “In the former report, IC50 titers as low as 1:8 were associated with protection from re-infection while in the latter, IC50 titers as low as 1:50 were associated with reduced viral load and protection from lung pathology.”

    From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [52]

  • Inactivated SARS-CoV-2 vaccine candidates have shown promising results in preclinical trials.

    “Inactivated SARS-CoV-2 vaccine candidates have shown promising results in preclinical trials.13, 14, 15”

    From Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey (2021) · cites this paper as [13]

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.

  • Safety-figure time points contradict the vaccination schedule

    Minor

    The stated vaccination days are 0, 7, and 14. Day 18 is 11 days after the second vaccination, not 3; day 29 is 15 days after the third, not 7; and day 1 is not the day of the first vaccination.

1 of 1

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Authors
Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang, M., Li, Y., Zhu, L., Wang, N., Lv, Z., Gao, H., Ge, X., Kan, B., Hu, Y., Liu, J., Cai, F., Jiang, D., Yin, Y., Qin, C., Li, J., Gong, X., Lou, X., Shi, W., Wu, D., Zhang, H., Zhu, L., Deng, W., Li, Y., Lu, J., Li, C., Wang, X., Yin, W., Zhang, Y., & Qin, C.
Affiliations
  • Sinovac Biotech (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Zhejiang Center for Disease Control and Prevention (CN)
  • National Institutes for Food and Drug Control (CN)
  • Chinese Academy of Sciences (CN)
  • Chinese Center For Disease Control and Prevention (CN)
  • Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China.
Corresponding author
  • Lu, Jinxing
  • Li, Changgui
  • Wang, Xiangxi
  • Yin, Weidong
  • Zhang, Yanjun
  • Qin, Chuan
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-07-03
Volume
369
Issue
6499
Pages
77-81
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.abc1932
PMC
PMC7202686
OpenAlex
W3022917947
Cited by
1,434
References
25
Citations by year
2026: 16 · 2025: 38 · 2024: 94 · 2023: 154 · 2022: 286 · 2021: 483 · 2020: 360 · 2019: 1
FWCI
42.28
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Greater South Information System
Funders
  • National Key Research and Development Program (2020YFA0707500)
  • Ten Thousand Talent Program and the NSFS Innovative Research Group (81921005)
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
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
Keywords
SARS-CoV-2, COVID-19 vaccines, inactivated vaccine, neutralizing antibodies, antibody-dependent enhancement, vaccine production, vaccine immunogenicity
MeSH terms
Immunogenicity, Vaccine, Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Antibodies, Viral, Chlorocebus aethiops, Dose-Response Relationship, Immunologic, Female, Immunoglobulin G, Macaca mulatta, Male, Mice, Inbred BALB C, Pilot Projects, Pneumonia, Viral, Vero Cells, Viral Vaccines, Vaccines, Inactivated, Rats, Wistar, Coronavirus Infections, Viral Load, 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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