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 protectionand its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination ismandatory for the management of the vaccination booster campaign. Our prospectivestudy was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine intriggering the cellular and humoral immune response in healthcare workers up to 12months after the initial vaccination, with one additional boosting dose between 6 and 12months.Methods: This prospective study enrolled 208 healthcare workers (HCWs) from the LiègeUniversity Hospital (CHU) of Liège in Belgium. Participants received two doses ofBioNTech/Pfizer COVID-19 vaccine (BNT162b2) and a booster dose 6-12 monthslater. Fifty participants were SARS-CoV-2 experienced and 158 were naïve before thevaccination. 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 12months (T5) after the second dose. Between T4 and T5, participants also got the thirdboosting 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 strainwere 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 usingthe QuantiFERON Human IFN-g SARS-CoV-2, Qiagen. We analyzed separately the naïveand experienced participants.Findings: We found that anti-spike antibodies and neutralization capacity levels weresignificantly higher in SARS-CoV-2 experienced HCWs compared to naïve HCWs at alltime points analyzed except the one after boosting dose. Cellular immune response wasalso higher in experienced HCWs six months following vaccination. Besides the impact ofSARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, weobserved a significant negative association between age and persistence of humoralresponse. The booster dose induced an increase in humoral and cellular immuneresponses, particularly in naive individuals. Breakthrough infections resulted in highercellular and humoral responses after the booster dose.Conclusions: Our data strengthen previous findings demonstrating that immunizationthrough vaccination combined with natural infection is better than 2 vaccine dosesimmunization or natural infection alone. The benefit of the booster dose was greater innaive individuals. It may have implications for personalizing mRNA vaccination regimensused to prevent severe COVID-19 and reduce the impact of the pandemic on thehealthcare system. More specifically, it may help prioritizing vaccination, including forthe deployment of booster doses.