Three-month follow-up of durability of response to the third dose of the SARS-CoV-2 BNT162b2 vaccine in adults aged 60 years and older: a prospective cohort study

  1. Noa Eliakim-Raz
  2. Amos Stemmer
  3. Yaara Leibovici-Weisman
  4. Asaf Ness
  5. Muhammad Awwad
  6. Nassem Ghantous
  7. Noam Erez
  8. Avital Bareket-Samish
  9. Adva Levy-Barda
  10. Haim Ben-Zvi
  11. Neta Moskovits
  12. Erez Bar-Haim
  13. Salomon M Stemmer

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Abstract

To evaluate the durability of response 3 months after the third BNT162b2 vaccine in adults aged 60 years and older.

Design

Prospective cohort study.

Setting

Single tertiary centre.

Participants

Healthcare workers/family members aged ≥60 years old who received the third BNT162b2 dose.

Interventions

Blood samples were drawn immediately before (T0), 10–19 days (T1) and 74–103 days (T2) after the third dose.

Primary and secondary outcome measures

Anti-spike IgG titres were determined using a commercial assay and seropositivity was defined as ≥50 arbitrary units (AU)/mL. Neutralising antibody titres were determined at T2. Adverse events, COVID-19 infections and Clinical Frailty Scale (CFS) levels were documented.

Results

The analysis included 97 participants (median age, 70 years (IQR, 66–74), 58% CFS level 2). IgG titres, which increased significantly from T0 to T1 (median, 440 AU/mL (IQR, 294–923) and median, 25 429 AU/mL (IQR, 14 203–36 114), respectively; p<0.001), decreased significantly by T2, but all remained seropositive (median, 8306 AU/mL (IQR, 4595–14 701), p<0.001 vs T1). In a multivariable analysis, only time from the second vaccine was significantly associated with lower IgG levels at T2 (p=0.017). At T2, 60 patients were evaluated for neutralising antibodies; all were seropositive (median, 1294 antibody titres; IQR, 848–2072). Neutralising antibody and anti-spike IgG levels were correlated (r=0.6, p<0.001). No major adverse events or COVID-19 infections were reported.

Conclusions

Anti-spike IgG and neutralising antibody levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults aged ≥60 years, although the decline in IgG is concerning. A third dose of vaccine in this population should be top priority.

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  1. Version published to 10.1136/bmjopen-2022-061584
  2. ScreenIT

    SciScore for 10.1101/2021.12.25.21268336: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Trial oversight: The trial was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Rabin Medical Center (RMC).
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    RandomizationIn T2, a second blood sample was drawn from 60 participants who were randomly selected for neutralisation antibody analysis and sent to the Israel Institute for Biological Research (Ness Ziona, Israel) where the SARS-CoV-2 pseudovirus neutralisation assay was performed.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Spearman correlation was used to assess the correlation between the anti-S IgG antibody values and neutralising antibodies titres.
    anti-S IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    , lentivirus backbone (psPAX, Addgen), and S genes (Δ19 S-covid-pCMV3, a kind gift from Prof. Yossef Shaul, Weizmann Institute of Science, Rehovot, Israel) were co-transfected into HEK293T cells (ATCC CRL-3216).
    HEK293T
    suggested: None
    , hACE2-expressing HEK293 cells were plated in a white-wall 96-well plate (2×104 cells per well).
    HEK293
    suggested: None
    Recombinant DNA
    SentencesResources
    Plasmids encoding a luciferase reporter (pGreenFire1, SystemBiosciences)
    pGreenFire1
    suggested: RRID:Addgene_112248)
    , lentivirus backbone (psPAX, Addgen), and S genes (Δ19 S-covid-pCMV3, a kind gift from Prof. Yossef Shaul, Weizmann Institute of Science, Rehovot, Israel) were co-transfected into HEK293T cells (ATCC CRL-3216).
    psPAX
    suggested: None
    Software and Algorithms
    SentencesResources
    Assessments: Titres of anti-S IgG antibodies in the serum from the blood samples were determined at the RMC microbiological laboratory, using a chemiluminescent microparticle immunoassay, performed on the Abbott architect i2000sr platform, in accordance with the manufacturer’s package insert for SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, IL, USA; reference 6S60-22).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Abbott Laboratories
    suggested: None
    IC50 titres were determined using a log (agonist) vs normalised-response (variable slope) nonlinear function using Prism software (GraphPad).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Study limitations include small sample size, lack of cellular immunity testing and lack of neutralising antibody testing in the first two timepoints. Although the accumulating evidence suggests that IgG response and neutralising antibodies are correlates of disease protection,27 cellular immunity is also suggested to play an important role in protecting against SARS-CoV-2.28 In conclusion, in our cohort of 97 adults aged 60 years and older, three months after the third BNT162b2 vaccine, high levels of anti-spike and neutralising antibodies were found, but with significant waning of the immune response. Although further studies are needed to advance our understanding of waning immunity, the results suggest that a third vaccine dose for adults aged 60 years and older is effective and should be a top priority worldwide.

    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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  3. Version published to 10.1101/2021.12.25.21268336v1 on medRxiv