Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint

  1. Xinhua Chen
  2. Wei Wang
  3. Xinghui Chen
  4. Qianhui Wu
  5. Ruijia Sun
  6. Shijia Ge
  7. Nan Zheng
  8. Wanying Lu
  9. Juan Yang
  10. Lance Rodewald
  11. Hongjie Yu

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Abstract

Background

Evidence on vaccine-specific protection over time, in particular against the Delta variant, and protection afforded by a homologous third dose is urgently needed.

Methods

We used a previously published model and neutralization data for five vaccines—mRNA-1273, BNT162b2, NVX-CoV2373, V01, and CoronaVac— to evaluate long-term neutralizing antibody dynamics and predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity.

Results

We found that homologous third-dose vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacy of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95% CI: 51.4–67.3%) and 78.4% (95% CI: 72.2–83.5%), respectively, 14–30 days after the second dose, and that efficacy decreases to 36.0% (95% CI: 24.1–58.0%) and 38.5% (95% CI: 28.7–49.1%) 6–8 months later. Fourteen to 30 days after administration of homologous third doses, efficacy against the Delta variant would be 97.0% (95% CI: 96.4–98.5%) and 97.2% (95.7–98.1%). All five vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and homologous third dose vaccination.

Conclusions

Timely administration of third doses of SARS-CoV-2-prototype-based vaccines can provide protection against the Delta variant, with better performance from mRNA vaccines than from protein and inactivated vaccines. Irrespective of vaccine technology, a homologous third dose for all types of vaccines included in the study will effectively prevent symptomatic and severe COVID-19 caused by the Delta variant. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody levels or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants, are needed to inform COVID-19 pandemic responses.

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  1. Version published to 10.1186/s12916-022-02249-9
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    SciScore for 10.1101/2021.09.23.21263715: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    14,21 In those studies, participants aged 18 years or older and vaccinated with CoronaVac were eligible for a study of the antibody kinetics of CoronaVac vaccine-induced SARS-CoV-2 neutralizing antibody.
    SARS-CoV-2 neutralizing antibody .
    suggested: None
    Software and Algorithms
    SentencesResources
    22 Neutralizing antibody dynamics with different vaccines with time-specific aggregated data collected from a comprehensive literature search: Using predefined search terms, we conducted a search for studies that reported dynamics of neutralizing antibodies and impact of a booster dose among vaccine recipients in five databases - three peer-reviewed databases (PubMed, Embase, and Web of Science) and two preprint servers (medRxiv, bioRxiv) (Appendix p10, Table S4).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    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:
    Our study has several limitations. First, our predictions depend on level of neutralizing antibodies, without taking other immunologic mechanisms of humoral and cellular immunity into account. However, previous studies showed that neutralizing antibodies are highly predictive of immune protection. Second, to enhance comparability between different studies with different neutralization assays, we normalized the neutralization titers in each study by the mean titers in convalescent sera reported in Phase I/II trials against prototype strains that used the same type of neutralization assay. However, other sources of heterogeneity, such as lab-to-lab variation and experimental procedures could not be accounted for. Third, the n-fold-reduction of neutralization titers of the Delta variant was not available for certain time periods for mRNA-1273. Instead, we used the n-fold-change from the Beta variant - a variant with more significant immune-escape capacity - to provide a conservative estimated for our analyses. We also conducted a sensitivity analysis by using n-fold-reduction from the Gamma variant (a variant with less significant immune-escape capacity than Delta). In conclusion, our study predicted time-varying vaccine protection from prototype SARS-CoV-2 and the Delta variant and the increase of protection that results from booster dose administration. We estimated protection by four COVID-19 vaccines from three clinical endpoints in two age groups. Our findings suggest that,...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

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  3. Version published to 10.1101/2021.09.23.21263715v1 on medRxiv