Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru

  1. Natalia Vargas-Herrera
  2. Manuel Fernández-Navarro
  3. Nestor E Cabezudo
  4. Percy Soto-Becerra
  5. Gilmer Solís-Sánchez
  6. Stefan Escobar-Agreda
  7. Javier Silva-Valencia
  8. Luis Pampa-Espinoza
  9. Ricardo Bado-Pérez
  10. Lely Solari
  11. Roger V Araujo-Castillo

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Abstract

Background

The administration of a third (booster) dose of COVID-19 vaccines in Peru initially employed the BNT162b2 (Pfizer) mRNA vaccine. The national vaccination program started with healthcare workers (HCW) who received BBIBP-CorV (Sinopharm) vaccine as primary regimen and elderly people previously immunized with BNT162b2. This study evaluated the reactogenicity and immunogenicity of the “booster” dose in these two groups in Lima, Peru.

Methods

We conducted a prospective cohort study, recruiting participants from November to December of 2021 in Lima, Peru. We evaluated immunogenicity and reactogenicity in HCW and elderly patients previously vaccinated with either two doses of BBIBP-CorV (heterologous regimen) or BTN162b2 (homologous regimen). Immunogenicity was measured by anti-SARS-CoV-2 IgG antibody levels immediately before boosting dose and 14 days later. IgG geometric means (GM) and medians were obtained, and modeled using ANCOVA and quantile regressions.

Results

The GM of IgG levels increased significantly after boosting: from 28.5±5.0 AU/mL up to 486.6±1.2 AU/mL (p<0.001) which corresponds to a 17-fold increase. The heterologous vaccine regimen produced higher GM of post-booster anti-SARS-CoV-2 IgG levels, eliciting a 13% fold increase in the geometric mean ratio (95%CI: 1.02-1.27) and a median difference of 92.3 AU/ml (95%CI: 24.9-159.7). Both were safe and well tolerated. Previous COVID-19 infection was also associated with higher pre and post-booster IgG GM levels.

Conclusion

Although both boosting regimens were highly immunogenic, two doses of BBIBP-CorV boosted with BTN162b2 produced a stronger IgG antibody response than the homologous BNT162b2 regimen in the Peruvian population. Additionally, both regimens were mildly reactogenic and well-tolerated.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.01.22274548: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Study procedures: Subjects meeting selection criteria were invited to participate in the study and signed an informed consent form.
    IACUC: Ethical considerations: The study protocol was approved by the National Institute of Health’s Institutional ethics committee (approval code: OI-35-21) and all participants signed a voluntary Informed Consent Form.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisHalf that sample size yielded >99% power to test if IgG ratios after boosting were different from 1, including a Bonferroni correction for ten simultaneous comparisons.

    Table 2: Resources

    Antibodies
    SentencesResources
    The main outcome was immunogenicity, assessed through SARS-CoV-2 anti-spike and anti-nucleoprotein IgG antibodies levels.
    SARS-CoV-2
    suggested: None
    anti-spike
    suggested: None
    anti-nucleoprotein IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    : StataCorp LLC. 2019).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    Some limitations in our study ought to be acknowledged. In the first place, all the participants were enrolled in vaccination centers from Lima through a non-probabilistic sampling, which could affect the representativeness of the general boosted population in Peru. Secondly, there was an important percentage of loss of follow-up, with almost a third of the enrolled participants not returning on time for their second blood sample. However, the sample size was still enough for a multivariate comparison of IgG levels pre/post booster, and there were no statistically significant differences between the people who completed the second visit and those who did not. An additional problem was the varying time between first and second IgG measurements; although the indication was to return 14 days +/-48 hours after boosting, a significant number came later, up to 28 days after boosting. Finally, we measured humoral response broadly, and did not include neutralizing antibodies or cellular immunity response, although binding antibody titers have been found to correlate with protective efficacy (28). On the other hand, one of the main strengths of our study is that we included a relatively large number of participants with different ages that were closely followed over time and thus the data obtained regarding immunogenicity and reactogenicity is reliable. We also had a relatable form of measuring prior COVID-19 infection and time of initial vaccines using the Peruvian Ministry of health...

    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

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  2. Version published to 10.1101/2022.05.01.22274548v1 on medRxiv