Declined Antibody Responses to COVID-19 mRNA Vaccine within First Three Months (preprint)

ABSTRACT

Background: Although the SARS-CoV-2 mRNA vaccines have proven high efficacy, limited data exists on the duration of immune responses and their relation to age and side effects.Methods: We studied the antibody and memory T cell responses to Spike protein after the two-dose Comirnaty mRNA vaccine in 122 volunteers up to 3 months and correlated the findings with age and side effects.Findings: We found a robust antibody response after the second vaccination dose. However, the antibody levels declined at 6 and 12 weeks postvaccination, indicating a waning of the immune response. Regardless, the average levels remained higher compared to pre-vaccination or in COVID-19 convalescent individuals. The antibodies efficiently blocked ACE2 receptor binding to Spike protein of four variants of concern at one week but this was decreased at three months, in particular with B.1.351 and P1 isolates. 87% of individuals developed Spike-specific memory T cell responses, which were lower in individuals with increased proportions of immunosenescent CD8+ TEMRA cells. We found a decreased vaccination efficacy but fewer adverse events in older individuals, suggesting a detrimental impact of age on outcome.Interpretation: The mRNA vaccine induces a strong antibody response to four variants at 1 week postvaccination but decreases thereafter, in particular among older individuals. T cell responses, although detectable in the majority, were lower in individuals with immunosenescence. The deterioration of vaccine response needs to be monitored to define the optimal time for the revaccination. Funding: The Estonian Research Council, Icosagen Cell Factory, and SYNLAB Estonia.Declaration of Interests None to declare. Ethics Approval Statement The study has been approved by the Research Ethics Committee of the University of Tartu on February 15, 2021 (No 335/T-21). Patients signed informed consent before recruitment into the study.