Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants Induced by Natural Infection or Vaccination: A Systematic Review and Pooled Analysis

  1. Xinhua Chen
  2. Zhiyuan Chen
  3. Andrew S Azman
  4. Ruijia Sun
  5. Wanying Lu
  6. Nan Zheng
  7. Jiaxin Zhou
  8. Qianhui Wu
  9. Xiaowei Deng
  10. Zeyao Zhao
  11. Xinghui Chen
  12. Shijia Ge
  13. Juan Yang
  14. Daniel T Leung
  15. Hongjie Yu

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Abstract

Recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may pose a threat to immunity. A systematic landscape of neutralizing antibodies against emerging variants is needed. We systematically searched for studies that evaluated neutralizing antibody titers induced by previous infection or vaccination against SARS-CoV-2 variants and collected individual data. We identified 106 studies meeting the eligibility criteria. Lineage B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) significantly escaped natural infection–mediated neutralization, with an average of 4.1-fold (95% confidence interval [CI]: 3.6–4.7-fold), 1.8-fold (1.4–2.4-fold), and 3.2-fold (2.4–4.1-fold) reduction in live virus neutralization assay, while neutralizing titers against B.1.1.7 (alpha) decreased slightly (1.4-fold [95% CI: 1.2–1.6-fold]). Serum from vaccinees also led to significant reductions in neutralization of B.1.351 across different platforms, with an average of 7.1-fold (95% CI: 5.5–9.0-fold) for nonreplicating vector platform, 4.1-fold (3.7–4.4-fold) for messenger RNA platform, and 2.5-fold (1.7–2.9-fold) for protein subunit platform. Neutralizing antibody levels induced by messenger RNA vaccines against SARS-CoV-2 variants were similar to, or higher, than that derived from naturally infected individuals.

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  1. Version published to 10.1093/cid/ciab646
  2. ScreenIT

    SciScore for 10.1101/2021.05.03.21256506: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We stratified the uninfected vaccine recipients by vaccine platforms (e.g., non-replicating vector, RNA, inactivated, and subunit protein) and the sampling interval post vaccination (i.e., <14 days, 14-90 days, and >90 days) based on a study that evaluated antibody persistence through 6 months after vaccination26.
    and subunit protein
    suggested: None
    Software and Algorithms
    SentencesResources
    Study Selection and Data Extraction: We conducted a systematic search from six databases, including three peer-reviewed databases (PubMed, Embase and Web of Science) and three preprint servers (medRxiv, bioRxiv and Europe PMC), for studies published in English between Sep 1, 2020 and Apr 18, 2021 with predefined search terms (Table S1).
    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, this study synthesized different neutralization assay results to estimate pooled GMTs. While we stratified analyses by neutralization assays according to virus types and vectors to get the most comparable results, significant variation between assays persists. Second, in many studies, individual-level details were not reported, thus limiting our ability to adjust for potential confounding factors in multivariate regression. We tried to contact study authors, but the response rate was generally low. Thirdly, we did not assess the impact of preexisting cellular immunity, which could provide a degree of protection as reported in previous studies38. In conclusion, our study provides a comprehensive mapping of the neutralizing potency against SARS-CoV-2 variants induced by natural infection or vaccination. Our findings suggest that immune sera/plasma retained most of its neutralizing potency against B.1.1.7 and B.1.427/ B.1.429 variants, but significantly lost neutralizing potency against B.1.351 and P.1 variants, with B.1.351 having the worst reductions. The evolution of SARS-CoV-2 lineage is still in process, and it’s unknown whether long-term accumulation of mutations can erode the neutralizing effectiveness of natural and vaccine elicited immunity, especially in the context of waning immunity. Therefore, longitudinal monitoring of emerging variants and antibody-induced immunity is of high importance, and standardized protocols for neut...

    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 10.1101/2021.05.03.21256506 on medRxiv