Neutralizing Antibody Response to Pseudotype Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Differs Between mRNA-1273 and BNT162b2 Coronavirus Disease 2019 (COVID-19) Vaccines and by History of SARS-CoV-2 Infection

  1. Harmony L Tyner
  2. Jefferey L Burgess
  3. Lauren Grant
  4. Manjusha Gaglani
  5. Jennifer L Kuntz
  6. Allison L Naleway
  7. Natalie J Thornburg
  8. Alberto J Caban-Martinez
  9. Sarang K Yoon
  10. Meghan K Herring
  11. Shawn C Beitel
  12. Lenee Blanton
  13. Janko Nikolich-Zugich
  14. Matthew S Thiese
  15. Jessica Flores Pleasants
  16. Ashley L Fowlkes
  17. Karen Lutrick
  18. Kayan Dunnigan
  19. Young M Yoo
  20. Spencer Rose
  21. Holly Groom
  22. Jennifer Meece
  23. Meredith G Wesley
  24. Natasha Schaefer-Solle
  25. Paola Louzado-Feliciano
  26. Laura J Edwards
  27. Lauren E W Olsho
  28. Mark G Thompson

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Abstract

Background

Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited.

Methods

From a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription–polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models.

Results

Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766–1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596–4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186–6926) compared with BNT162b2 vaccine (GMT, 2309; 1825–2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766–31 756) after mRNA vaccine dose 1, without further increase after dose 2.

Conclusions

A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product.

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  1. Version published to 10.1093/cid/ciab1038
  2. ScreenIT

    SciScore for 10.1101/2021.10.20.21265171: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: At the time of enrollment, all participants provided written consent.
    IRB: This study was reviewed and approved by Institutional Review Boards (IRBs) at each of the participating institutions.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The resulting serum-neutralizing antibodies were calculated as the 50% inhibitory dilution (ID50).
    ID50
    suggested: (bNAber Cat# bNAberID_50, RRID:AB_2491067)
    These serologic assays, which quantify the amount of host serum needed to neutralize pseudovirus infectivity, an in-vitro proxy for antibody mediated protection against SARS-CoV-2, were conducted by LabCorp (South San Francisco, CA) staff blinded to SARS-CoV-2 infection status and vaccine product (Supplementary Appendix: Methods)[14].
    SARS-CoV-2
    suggested: None

    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:
    This study also has at least six limitations. First, nAb responses could only be examined within the time intervals of vaccination that occurred in our study. Inferences regarding antibody response following mRNA vaccine dose-1 are limited to the 2 to 3 weeks between vaccine doses, because most individuals had their second vaccine dose at the shortest recommended time interval. Second, serum-neutralizing antibodies were measured against USA-WA1/2020-spike pseudotype virus rather than with a live virus assay. However, previous studies have shown concordance between nonreplicating pseudotype neutralization and SARS-CoV-2 neutralization assays [39, 40]. Third, the nAb assays against USA-WA1/2020-spike pseudotype virus were performed by LabCorp using the PhenoSense® assay. The assay was validated before WHO standards were widely available, and the results are not reported in international units, therefore they are not directly translatable to assays performed by other laboratories. Fourth, cellular mediated immunogenicity could not be examined, which additionally contributes to clinical protection. In the same cohort, high vaccine effectiveness was noted in preventing SARS-CoV-2 infection starting 14 days after mRNA vaccine dose 1 [12]. Fifth, because of sparse data and limited sociodemographic and health heterogeneity, we were unable to fully examine or adjust for factors that may be associated with immune response to infection or vaccination. Data represented here was collected...

    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.
    • Thank you for including a protocol registration statement.

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

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  3. Version published to 10.1101/2021.10.20.21265171v1 on medRxiv