Evolution of Antibody Titers Up to 6 Months Post-Immunization With the BNT162b2 Pfizer/BioNTech Vaccine in Greece

Abstract

Background: Despite accumulating evidence of the durable effectiveness of the BNT162b2 mRNA Covid-19 vaccine over time, there is a lack of phase IV studies reporting data on long-term vaccine-induced immunogenicity in specific population groups like healthcare workers. The aim of the present study was to comprehensively assess the 6-month course of humoral immune responses elicited by the BNT162b2 vaccine among healthcare workers in Greece.

Methods: We employed theSARS-CoV-2 IgG II Quant assay on the Architect Systemto longitudinally assess titers of neutralizing IgG against the receptor-binding domain of the S1 subunit of the spike protein in participant-derived serum samples.

Results: Our study encompassed 252 participants whose anti-RBD IgG titers were monitored through the course of six months. The overall IgG GMC almost doubled compared to its value 14 days after the first dose (fold change=1.954) yet declined by 94% compared to its levels 14 days after the second dose (fold change =0.061) and by 66% compared to its 3-month value (fold change =0.335). However, in 99% of our sample antibody titers exceeded the seropositivity threshold of 50 AU/ml. A substantial discrepancy in antibody levels was observed upon history of infection (p-value<0.001). Further, a statistically significant difference was noted in antibody titers between age groups (p-value<0.001). Specifically, antibody titers of subjects in the 60-69 age group (GMC=568.05 AU/ml) had significantly lower levels than in subjects aged less than 50 years old.

Further statistical modeling revealed that in subjects aged under 60, antibody titers marked a decline from 10000 to 1000 (from 4 to 3 in the log10 scale) within 6 months’ time, whereas the same effect was observed in 4 months among vaccinated individuals aged over 60. Prognostic results obtained from the modeling procedure suggest that subjects with a positive history of infection that received both doses of the vaccine will probably notice such a drop in their antibody titers well beyond one-year post-immunization

Compared to antibody levels post-2nd dose, males and uninfected subjects marked a greater 6-month decline than their counterparts, while age did not seem to affect antibody trends within that time span. Lastly, the drop of antibody titers observed from 3 to 6 months post-immunization was homogenous in both genders and age groups, only varying upon history of infection.

Conclusion: Our findings are highly indicative of the durable antibody responses generated by the BNT162b2 vaccine in all age groups, while highlighting the significantly slower decline of antibody titers in the previously infected. This evidence suggests that the long-term antibody trajectories observed in the seropositive group are potentially equivalent to the benefit of a third dose given to the uninfected, safeguarding the longevity of their humoral immunity over time.

Note: Funding: None.

Declaration of Interests: None.

Ethics Approval Statement: The study protocol was reviewed and approved by the ethics committee of the scientific council of the G. Gennimatas General Hospital (protocol number:1/13.1.2021).

Trial Registration: The trial is registered on the International Standard Randomized Controlled Trial Number registry (study ID: ISRCTN61884303).

Keywords: BNT162b2 mRNA Covid-19 vaccine; immunogenicity; antibodies; SARS-CoV-2; 6-months post-vaccination; healthcare workers, Greece