The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index; 11 of the 13 sources its claims cite were checked for support.
Development of an inactivated vaccine candidate for SARS-CoV-2
Open accessPublished version of a preprint
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
Overview
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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.
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Claims the paper makes
11 of 13 cited sources checked · 2 supported · 1 flagged · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“The “cytokine storm” induced by excessive T-cell responses have been actually shown to accentuate the pathogenesis of COVID19 (18, 19).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
- Disputedcites [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 sourceExperimental — accuracy not yet measured
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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“which closely matches the serological profile of the blood of recovered COVID-19 patients (Fig. 2, A and B) (11).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“protection from subsequent coronavirus infections is largely mediated by humoral immunity (16, 17).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Partly supportedcites [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). sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Not checked — no full text of the sourcecites [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
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesEvery source the paper cites for this claim was checked and supports it.
In the paper
“the antibodies targeting N of SARS-CoV-2 do not provide protective immunity against the infection (12)”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Supportedcites [12] 12. Gralinski L. E., Menachery V. D., Return of the coronavirus: 2019-nCoV. Viruses 12, E135 (2020). 10.3390/v12020135 source
Section 4, “Insights from the 2019-nCoV Sequence,” explicitly states that N antibodies do not provide immunity to 2019-nCoV infection. The citing sentence accurately paraphrases that statement. (LLM, conf=0.95)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“rhesus macaques (Macaca mulatta), a non-human primate species that shows a COVID-19-like disease caused by SARS-CoV-2 infection (13).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Supportedcites [13] 13. Yu P., Qi F., Xu Y., Li F., Liu P., Liu J., Bao L., Deng W., Gao H., Xiang Z., Xiao C., Lv Q., Gong S., Liu J., Song Z., Qu Y., Xue J., Wei Q., Liu M., Wang G., Wang S., Yu H., Liu X., Huang B., Wang W., Zhao L., Wang H., Ye F., Zhou W., Zhen W., Han J., Wu G., Jin Q., Wang J., Tan W., Qin C., Age-related rhesus macaque models of COVID-19. Animal Model. Exp. Med. 3, 93–97 (2020). 10.1002/ame2.12108 source
The Methods describe infecting rhesus macaques (Macaca mulatta) with SARS-CoV-2. The Results and Discussion report clinical signs, viral replication, and interstitial pneumonia after infection, supporting the description of a COVID-19-like disease. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively”
- Also stated in: § Abstract · boosted
“Our data also demonstrate a complete protection against SARS-CoV-2 challenge with a 6μg per dose of PiCoVacc in macaques.”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates.”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“without observable antibody-dependent enhancement of infection.”
- Also stated in: § Abstract · plain
“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.”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
- Probably not a substantial claim. 3
- It may state two separate claims as one. 17
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Not checked — no full text of the sourcecites [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
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“all vaccinated macaques were largely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that PiCoVacc CN2 strain possesses excellent genetic stability without the S mutations that might potentially alter the NAb epitopes.”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Development of an inactivated vaccine candidate for SARS-CoV-2 > Abstract
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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).”
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The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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 Alphavirus -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]
The cited source says what the claim attributes to it.
In the citing paper
“Inactivated SARS-CoV-2 vaccine candidates have shown promising results in preclinical trials.13, 14, 15”
The cited source says what the claim attributes to it.
In the citing paper
“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).”
From Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2 (2020) · cites this paper as Gao et al., 2020
In the citing paper
“Several non-human primate COVID-19 vaccine studies are consistent with the possibility of COVDI-19 vaccines preventing severe disease in humans but possibly not preventing URT infection”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Gao et al., 2020
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
MinorThe 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.
“Lymphocyte subset percents (A), including CD3+, CD4+ and CD8+ were monitored at day -1 (1 day before vaccination), 18 (3 days after the second vaccination) and 29 (7 days after the third vaccination). Key cytokines (B), containing TNF-α, IFN-γ and IL-2 were examined at day -1, 1 (the day of the first vaccination), 4, 18 and 29 after vaccination.”
“Macaques were immunized three times at day 0, 7 and 14 through the intramuscular route”
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Self-citationMolecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy
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COVID-19 in early 2021: current status and looking forward
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Self-citationThe COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation
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Lessons for COVID-19 immunity from other coronavirus infections
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COVID-19 Transmission, Current Treatment, and Future Therapeutic Strategies
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Self-citationA materials-science perspective on tackling COVID-19
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COVID-19 pandemic: Insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2
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Self-citationAd26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters
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Self-citationWuhan to World: The COVID-19 Pandemic
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Self-citationComparison of nonhuman primates identified the suitable model for COVID-19
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Metadata
- 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
- Gao, Qiang
- Bao, Linlin
- Mao, Haiyan
- Wang, Lin
- Xu, Kangwei
- Yang, Minnan
- Li, Yajing
- Zhu, Ling
- Wang, Nan
- Lv, Zhe
- Gao, Hong
- Ge, Xiaoqin
- Kan, Biao
- Hu, Yaling
- Liu, Jiangning
- Cai, Fang
- Jiang, Deyu
- Yin, Yanhui
- Qin, Chengfeng
- Li, Jing
- Gong, Xuejie
- Lou, Xiuyu
- Shi, Wen
- Wu, Dongdong
- Zhang, Hengming
- Zhu, Lang
- Deng, Wei
- Li, Yurong
- Lu, Jinxing
- Li, Changgui
- Wang, Xiangxi
- Yin, Weidong
- Zhang, Yanjun
- Qin, Chuan
- Venue
- Science
- Published
- 2020-07-03
- Volume
- 369
- Issue
- 6499
- Pages
- 77-81
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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
- FWCI
- 42.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- 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.
A language model drew the claims from the paper on 2026-10-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (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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