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. 2022 Mar 2:13:842912.
doi: 10.3389/fimmu.2022.842912. eCollection 2022.

Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers

Benjamin Bonnet  1   2 , Hélène Chabrolles  3   4 , Christine Archimbaud  3   4 , Amélie Brebion  3 , Justine Cosme  1 , Frédéric Dutheil  5   6 , Céline Lambert  7 , Maud Junda  1 , Audrey Mirand  3   4 , Amandine Ollier  8 , Bruno Pereira  7 , Christel Regagnon  3 , Magali Vidal  9 , Bertrand Evrard  1   2 , Cécile Henquell  3   4
Affiliations

Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers

Benjamin Bonnet et al. Front Immunol. .

Abstract

Clinical trials and real-world evidence on COVID-19 vaccines have shown their effectiveness against severe disease and death but the durability of protection remains unknown. We analysed the humoral and T-cell immune responses in 110 healthcare workers (HCWs) vaccinated according to the manufacturer's recommended schedule of dose 2 three weeks after dose 1 from a prospective on-going cohort in early 2021, 3 and 6 months after full vaccination with the BNT162b2 mRNA vaccine. Anti-RBD IgG titres were lower in HCWs over 60 years old 3 months after the second dose (p=0.03) and declined in all the subjects between 3 and 6 months with a median percentage change of -58.5%, irrespective of age and baseline comorbidities. Specific T-cell response measured by IGRA declined over time by at least 42% (median) in 91 HCWs and increased by 33% (median) in 17 others. Six HCWs had a negative T-cell response at 6 months. Ongoing follow-up should provide correlates of long-term protection according to the different immune response profiles observed. COVIDIM study was registered under the number NCT04896788 on clinicaltrials.gov.

Keywords: B cell response; COVID-19; T cell response; interferon gamma (IFNγ); mRNA vaccine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Humoral and specific T-cell responses in 110 healthcare workers 3 and 6 months after the second dose of the BNT162b2 mRNA vaccine. Evolution over time of (A) serum anti-RBD IgG antibodies and (B) IFN-γ secreting memory T-cells via an Interferon-Gamma Release Immunoassay that uses two mixes of SARS-CoV-2 spike protein (Ag.1 and Ag.2) selected to activate both CD4+ and CD8+ T-cells. Box and whiskers plot indicate median and interquartile range associated with min to max. All participants are indicated, and sex is discriminated by grey (women) or black (men) circle. Black dotted lines represent respective positive thresholds (p<0.001 versus M3, linear mixed-effects models). Number of cases for each time point (a) M3, 110; M6, 110; (b) M3, 108; M6, 110. BAU, binding antibody unit; IFN-γ, interferon gamma; IU, international unit; M3, 3 months post complete vaccination; M6, 6 months post complete vaccination; RBD, receptor-binding domain.
Figure 2
Figure 2
Correlation between humoral and T-cell responses 3 and 6 months after the second dose of BNT162b2 mRNA vaccine. Scatter plot of specific IFN-γ response and anti-RBD IgG over time following BNT162b2 vaccination (n=108 at M3 and n=110 at M6). The full line represents the best fit linear relationship of data. Pearson’s correlation coefficients are indicated (rho). BAU, binding-antibody unit; IFN-γ, interferon gamma; IU, international unit; M3, 3 months post complete vaccination; M6, 6 months post full vaccination; RBD, receptor-binding domain.
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