Kinetics and persistence of anti-SARS-CoV-2 neutralisation and antibodies after BNT162b2 vaccination in a Swiss cohort

Abstract

Introduction: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), substantial effort has been made to gain knowledge about the immunity elicited by infection or vaccination.

Methods: We studied the kinetics of antibodies and virus neutralisation induced by vaccination with BNT162b2 in a Swiss cohort of SARS-CoV-2 naïve (n = 40) and convalescent (n = 9) persons. Blood sera were analysed in a live virus neutralisation assay and specific IgG and IgA levels were measured by enzyme-linked immunoassay and analysed by descriptive statistics.

Results: Virus neutralisation was detected in all individuals 2-4 weeks after the second vaccine. Both neutralisation and antibodies remained positive for >4 months. Neutralisation and antibodies showed positive correlation, but immunoglobulin G (IgG) and immunoglobulin A (IgA) seroconversion took place 2-4 weeks faster than neutralisation. Spike-protein specific IgG levels rose significantly faster and were more stable over time than virus neutralisation titres or IgA responses. For naïve but not convalescent persons, a clear boosting effect was observed. Convalescent individuals showed faster, more robust and longer-lasting immune responses after vaccination compared to noninfected persons. No threshold could be determined for spike protein-specific IgG or IgA that would confer protection in the neutralisation assay, implicating the need for a better correlate of protection then antibody titres alone.

Conclusions: This study clearly shows the complex translation of antibody data and virus neutralisation, while supporting the evidence of a single dose being sufficient for effective antibody response in convalescent individuals.

Trial registration: ClinicalTrials.gov NCT04979871.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; antibody response; mRNA vaccine; neutralisation assay.

Figure 1

Fast and strong SARS‐CoV‐2 neutralisation after vaccination with BNT162b2 in convalescent persons. Two cohorts of naïve (left panel/red; n = 40) and convalescent (right/blue; n = 9) were defined based on history of COVID‐19 before first vaccination (Day 0). Secondary vaccination was done approximately 4 weeks after the first vaccine dose. Convalescent subjects received first vaccination 3–12 months after infection. (A) Reciprocal titres of SARS‐CoV‐2 neutralising antibodies measured using a tissue‐culture infection dose‐based method. The donut charts illustrate the fraction of persons with positive (red or blue) virus neutralisation at time points indicated in the figures underneath. The numbers in the donut centres indicate the number of persons analysed at the given time point. The inset (right panel) represents neutralisation titters of convalescent individuals 4–12 weeks postinfection, but before vaccination. Neutralisation titres equal or bigger than 40, as indicated by the dashed line, are considered as positive. (B) Spike (S1) protein‐specific IgG in BAU/ml as measured by ELISA. (C) Spike protein‐specific IgA in in OD‐ratio and as measured by ELISA. (D) Virus neutralisation titres of serum from naïve participants was measured as a function of time after the first (left panel) and the second (right panel) vaccination. Neutralisation data are illustrated as geometric means with 95% confidential intervals of the means, while IgG and IgA data are illustrated as medians with 95% CI. Nonparametric Kruskal–Wallis test with Dunn's test were applied to compare samples at each time point with the following one. All p values lower than 0.05 were considered statistically significant and p values >0.0001 were indicated as exact numbers. COVID‐19, coronavirus disease 2019; ELISA, enzyme‐linked immunoassay; IgA, immunoglobulin A; IgG, immunoglobulin G; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2 [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Modelling of virus neutralisation and antibodies kinetics. Anti‐SARS‐CoV‐2 neutralisation (A), IgG response (B), and IgA response (C) are stratified in convalescent (blue) and naïve (red) according to the COVID‐19 history of the participants before vaccination on Day 0 and approximately 4 weeks later. Serum samples collected within 100 days of the primary vaccination were included in the analysis. Regression curves (lines) and 95% CI (shades) are shown. CI, confidence interval; COVID‐19, coronavirus disease 2019; IgA, immunoglobulin A; IgG, immunoglobulin G; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2 [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Strong correlation between SARS‐CoV‐2‐specific IgG and IgA antibodies. Correlation analyses are performed in the naïve cohort and spike protein‐specific IgG and IgA antibody concentration and anti‐SARS‐CoV‐2 neutralisation titres are compared for each person at each blood donation (n = 176). Correlation plot between reciprocal neutralising titres and spike‐protein‐specific IgG (A) or IgA (B) and antibody titres. (C) Correlation plot between neutralisation and a combined IgG and IgA factor (the product of IgG and IgA concentrations). (D) Correlation plot of IgG and IgA. Spearman correlation coefficients (ρ), 95% CI values and P values are indicated above the graphs and plotted as hatched linear regression lines with shaded 95% CI. CI, confidence interval;IgA, immunoglobulin A; IgG, immunoglobulin G; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2 [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Peak virus neutralisation titres of naïve individuals after first and after second vaccination are independent of gender and age. Virus neutralisation titres are shown after the first and the second vaccination for all naïve individuals and represented also according to gender (men/women) and age (>50 years or <50 years). The numbers in bracket in the upper part of the graph indicate in each group the number of persons that donated blood after the first and after the second dose. Statistical analysis was performed using Kruskal–Wallis test (nonparametric one‐way ANOVA) with Dunn's multiple comparison test. All p values lower than .05 were considered statistically significant and p values >.0001 were indicated as exact numbers. ANOVA, analysis of variance [Color figure can be viewed at wileyonlinelibrary.com]