A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

Abstract

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; antibody response; mRNA vaccine; neutralization; previous infection; response predictors; variants.

Graphical abstract

Figure 1

Anti-SARS-CoV-2 IgG responses (A) Post-infection serum IgG levels in SARS-CoV-2 S and RBD protein. The posterior median decay slope and its 95% credible interval are plotted as black and gray lines, respectively. (B) Pre- (week 0 = before first dose, n = 150 participants) and post-vaccination (week 4 = before second dose, n = 101 participants) as well as HCW control (n = 49) distributions of serum IgG levels to SARS-CoV-2 S and RBD proteins. (C) Pre- (week 0; n = 30 participants) and post-vaccination (week 1, n = 30 participants, and week 8, n = 21 participants) distributions of anti-S IgG levels to WT (Wuhan-Hu-1) and VOC lineages Alpha, Beta, Gamma, and Delta. Each point represents 1 participant colored by COVID-19 severity. ∗: distributions with non-overlapping 95% confidence interval (CI) of group mean effect size estimated using a Bayesian ANOVA model (Table S2). Median with interquartile range is depicted. Areas of binding values below detection limit are shaded in gray.

Figure 2

Serum neutralization of SARS-CoV-2 pseudovirus (A) Post-infection serum neutralization levels to SARS-CoV-2. The posterior 2-phase median decay slope and its 95% credible interval are plotted as black and gray lines, respectively. The posterior median transition time point between the 2 phases is indicated as a dashed vertical line. (B) Pre- (week 0 = before first dose, n = 150 participants), post-vaccination (week 4 = before second dose, n = 101 participants), and HCW control (n = 49) distributions of SARS-CoV-2 pseudovirus neutralization. (C) Pre-vaccination (week 0, n = 30 participants) and post-vaccination (week 1, n = 30 participants, and week 8, n = 21 participants) serum neutralization distributions of WT D614G and VOC lineages Alpha, Beta, Gamma, and Delta. Each point represents 1 participant colored by COVID-19 severity. ∗: distributions with non-overlapping 95% CI of group mean effect size estimated using a Bayesian ANOVA model (Table S4). Median with interquartile range is depicted. Areas of neutralization titers below detection limit are shaded in gray.

Figure 3

Predictors of vaccine response (A and B) Joint contributions of participant and clinical factors on post-vaccination serum neutralization titers on weeks 1 (A) and 4 (B) after the first vaccine dose. The mean effects across study participants were estimated using a Bayesian multilevel model. All continuous predictors were mean centered and scaled such that effect sizes shown can be compared on a common scale (sex: male encoded as 0 and female encoded as 1). (C) Distributions of pre- (week 0) and post-vaccination (weeks 1 and 4) in serum neutralization titers of study participants stratified according to time since symptom onset. Each point represents 1 participant colored by COVID-19 severity. ∗: distributions with non-overlapping 95% CI of group mean effect size estimated using a Bayesian ANOVA model (Table S4). Median with interquartile range is depicted. Areas of neutralization titers below detection limit are shaded in gray.