Inactivated Vaccines Against SARS-CoV-2: Neutralizing Antibody Titers in Vaccine Recipients

  1. Haiying Zhang
  2. Yuyuan Jia
  3. Ying Ji
  4. Xu Cong
  5. Yan Liu
  6. Ruifeng Yang
  7. Xiangsha Kong
  8. Yijun Shi
  9. Ling Zhu
  10. Zhenyu Wang
  11. Wei Wang
  12. Ran Fei
  13. Feng Liu
  14. Fengmin Lu
  15. Hongsong Chen
  16. Huiying Rao

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Abstract

Although effective vaccines have been developed against coronavirus disease 2019 (COVID-19), the level of neutralizing antibodies (NAbs) induced after vaccination in the real world is still unknown. The aim of this work was to evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China.

Methods

Serum samples were collected from 1,335 people aged 18 years and over who were vaccinated with an inactivated COVID-19 vaccine at Peking University People’s Hospital from January 19 to June 23, 2021, for the detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies.

Results

The positive rate for NAbs against SARS-CoV-2 was 79–91% from the first month to the second month after the second vaccine dose. The gradual decline in positivity rate for NAb response was observed from 78% at 3 months post-vaccination to 0% at 12 months post-vaccination. When there was a 21-day interval between the two doses of vaccine, the NAb positivity rate was 0% 6 months after the second dose. NAb levels were significantly higher when the interval between two doses were 3–8 weeks than when it was 0–3 weeks (χ2 = 14.04, p < 0.001). There was a linear correlation between NAbs and IgG antibodies in 1,335 vaccinated patients. NAb levels decreased in 31 patients (81.6%) and increased in 7 patients (18.4%) over time in the series of 38 patients after the second vaccination. The NAb positivity rate was significantly higher in 18- to 40-year-old subjects than in 41- to 60-year-old subjects ( t = − 1 . 959 , p < 0 . 01 ; t = 0 . 839 , p < 0 . 01 ).

Conclusion

The NAb positivity rate was the highest at the first and second month after the second dose of vaccine, and gradually decreased over time. With a 21-day interval between two doses of vaccine, neutralizing antibody levels persisted for only 6 months after the second dose of vaccine. Therefore, a third vaccine dose is recommended. Our results suggest that in cases in which NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age but not by sex. Our results suggest that an interval of 21 to 56 days between shots is suitable for vaccination.

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  1. Version published to 10.3389/fmicb.2022.816778
  2. ScreenIT

    SciScore for 10.1101/2021.08.18.21262214: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: This study was approved by the ethics committee of the Peking University People’s Hospital.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Magnetic particles were coated with 2019-nCoV antigen, and anti-human IgG antibody was labeled with horseradsh peroxidase to prepare enzyme conjugals.
    antigen,
    suggested: None
    anti-human IgG
    suggested: None
    The complex catalyzed luminescence substrate to give off photoperites, and the luminescence intensity was proportional to the content of COVID-19 IgG antibody.
    COVID-19 IgG
    suggested: None
    Quality control: Each test batch of the above two kits includes negative quality control products and positive quality control products for COVID-19 antibody/nutralization antibody.
    antibody/nutralization
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: SPSS 21.0 was used for software analysis.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations of this study. For one thing, the study did not include pregnant women or people under 18 years old. Therefore, the real-world effectiveness of inactivated vaccines in these populations remains unknown. In the next step, the effective protective concentration of COVID-19 neutralizing antibody can be determined through research, for example, the critical value of hepatitis B virus surface antibody is 10 mIU/mL. In summary, the positive rate of neutralization antibody was the highest at 10-70 days after the second dose of vaccine, and gradually decreased with the passage of time. Therefore, the third dose of vaccine was recommended at about 70 days.our study shows that COVID-19 IgM/IgG antibodies can be detected in cases where NAbs cannot be detected. 21-56 days(3-8 week) between the two doses was suitable for vaccination. Our study provides an important insight into real-world vaccination cycles, vaccination timing, and detection methods.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.08.18.21262214 on medRxiv