Kinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects: impact of booster dose and breakthrough infections

Background: Understanding and measuring the individual level of immune protection
and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is
mandatory for the management of the vaccination booster campaign. Our prospective
study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in
triggering the cellular and humoral immune response in healthcare workers up to 12
months after the initial vaccination, with one additional boosting dose between 6 and 12
months.Methods: This prospective study enrolled 208 healthcare workers (HCWs) from the Liège
University Hospital (CHU) of Liège in Belgium. Participants received two doses of
BioNTech/Pfizer COVID-19 vaccine (BNT162b2) and a booster dose 6-12 months
later. Fifty participants were SARS-CoV-2 experienced and 158 were naïve before the
vaccination. Blood sampling was performed at the day of the first (T0) and second (T1)
vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3), 6 months (T4) and 12
months (T5) after the second dose. Between T4 and T5, participants also got the third
boosting vaccine dose. A total of 1145 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies, using the DiaSorin LIAISON SARS-CoV2 TrimericS IgG assay, and for anti-Nucleocapsid antibodies, using Elecsys anti-SARSCoV-2 assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain
were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cellmediated immune response was evaluated at T4 and T5 on 80 and 55 participants,
respectively, by measuring the secretion of IFN-g on peripheral blood lymphocytes using
the QuantiFERON Human IFN-g SARS-CoV-2, Qiagen. We analyzed separately the naïve
and experienced participants.
Findings: We found that anti-spike antibodies and neutralization capacity levels were
significantly higher in SARS-CoV-2 experienced HCWs compared to naïve HCWs at all
time points analyzed except the one after boosting dose. Cellular immune response was
also higher in experienced HCWs six months following vaccination. Besides the impact of
SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we
observed a significant negative association between age and persistence of humoral
response. The booster dose induced an increase in humoral and cellular immune
responses, particularly in naive individuals. Breakthrough infections resulted in higher
cellular and humoral responses after the booster dose.
Conclusions: Our data strengthen previous findings demonstrating that immunization
through vaccination combined with natural infection is better than 2 vaccine doses
immunization or natural infection alone. The benefit of the booster dose was greater in
naive individuals. It may have implications for personalizing mRNA vaccination regimens
used to prevent severe COVID-19 and reduce the impact of the pandemic on the
healthcare system. More specifically, it may help prioritizing vaccination, including for
the deployment of booster doses.