Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study

Abstract

Background: SARS-CoV-2 mRNA vaccines have proven high efficacy, however, 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 after the two-dose BNT162b2 vaccine in 122 volunteers up to 6 months and correlated the findings with age and side effects.

Findings: We found a robust antibody response to Spike protein after the second dose. However, the antibody levels declined at 12 weeks and 6 months post-vaccination, indicating a waning of the immune response over time. At 6 months after the second dose, the Spike antibody levels were similar to the levels in persons vaccinated with one dose or in COVID-19 convalescent individuals. The antibodies efficiently blocked ACE2 receptor binding to SARS-CoV-2 Spike protein of five variants of concern at one week but this was decreased at three months. 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 antibody response to correlate negatively with age and positively with the total score of vaccination side effects.

Interpretation: The mRNA vaccine induces a strong antibody response to SARS-CoV-2 and five VOCs at 1 week post-vaccination that decreases thereafter. T cell responses, although detectable in the majority, were lower in individuals with higher T cell immunosenescence. The deterioration of vaccine response suggests the need to monitor for the potential booster vaccination.

Keywords: SARS-CoV-2 mRNA vaccine; adverse effects; age; dynamics of the immune response.

Fig. 1

Antibody responses in individuals vaccinated with Pfizer-BioNTech Comirnaty vaccine. S-RBD IgG levels before vaccination (B1D, n=88), after the single (B2D, n=111) and two-dose immunizations (1 week (1wA2D, n=106); 6 weeks (6wA2D, n=89), 12 weeks (12wA2D, n=90), and 6 months (6mA2D; n=84) in vaccinated individuals compared with post-infection levels in patients recovered from COVID-19 (COVID-19, n=97) and pre-COVID-19 negative controls (NC, n=50). The box plot comparisons were performed with the Kruskall-Wallis test and Dunn's multiple testing correction; p-values >0·0001 are reported as exact numbers.

Fig. 2

Inhibition of ACE2-trimeric Spike interaction by vaccine-induced antibodies. Serum antibody capacities to block the interaction of ACE2 receptor and Spike protein with the modifications of wild type (wt, Wuhan, n=49) and five VOCs of Alpha (B.1.1.7, n=49), Beta (B.1.351, n=49), Gamma (P.1, n=49), Delta (B.1.617.2, n=48), and Kappa (B.1.617.1, n=48) were analyzed before the vaccination (B1D), one (1wA2D) and 12 (12wA2D) weeks after the second dose. The dotted line indicates the relative OD value of 0·75, which is a threshold for sufficient blocking of ACE2 binding. The box plot comparisons were performed with the Kruskal-Wallis test with Dunn's multiple testing correction; p-values >0·0001 are reported as exact numbers.

Fig. 3

Spike-specific T cell responses in vaccinated individuals 12 weeks after the second dose. (A) Post-vaccination frequency of S-specific CD4⁺ (n=79) and CD8⁺ (n=78) T cells and (B) the percentage of Spike-specific CD4+ T cells in individuals with lower (<40%, n=61) and higher (>40%, n=17) proportions of CD8⁺ TEMRA cells in their peripheral blood. The data were analyzed with the Mann-Whitney test, two-tailed p-values are given as exact numbers.

Fig. 4

Post-vaccination antibody responses correlate negatively with age. Spearman correlation analysis between age and S-RBD IgG levels before the second dose (B2D, n=111), 1 week (1wA2D, n=106), 6 weeks (6wA2D, n=89), 12 weeks (12wA2D, n=90), and 6 months (6mA2D, n=84) after the second dose. Spearman correlation coefficient and exact p-values are given.

Fig. 5

Post-vaccination antibody responses correlate positively with the total score of side effects. Spearman correlation analysis between total score of side effects and S-RBD IgG levels before the second dose (B2D, n=84), 1 week (1wA2D, n=85), 6 weeks (6wA2D, n=82), 12 weeks (12wA2D, n=82), and 6 months (6mA2D; n=75) after the second dose. Spearman correlation coefficient and exact p-values are given.