Robust Antibody Responses to the BNT162b2 mRNA Vaccine Occur Within a Week After the First Dose in Previously Infected Individuals and After the Second Dose in Uninfected Individuals

Abstract

Background: Vaccines against severe acute respiratory syndrome coronavirus 2 can trigger acquired immunity in infection-naïve individuals and offer a path toward ending the coronavirus disease pandemic that began in 2019. However, the kinetics of early antibody responses in vaccinated individuals remain poorly understood.

Method: We followed BNT162b2 mRNA-vaccinated health care workers (HCWs, N=108) including 103 infection-naïve and five previously infected individuals. A total of 763 blood samples were collected weekly or hourly basis before and after vaccination. Serological analysis of anti-spike and anti-nucleocapsid antibodies was performed.

Results: Seroconversion occurred in all infection-naïve HCWs 3 weeks after the first dose (just before the second vaccination) and a marked boosting effect was observed at 4 weeks (1 week after the second dose). Among previously infected HCWs with pre-existing antibodies against the spike protein, a remarkable boosting effect was observed during the first week after vaccination, and a further increase in antibody titres was observed after the second dose. In one previously infected patient, daily blood sampling was conducted. Antibody titres began to increase 96 hours (4 days) after the first dose.

Conclusion: The BNT162b2 mRNA vaccine remarkably enhanced antibody responses after the second dose in infection-naïve individuals and after the first dose in previously infected HCWs of all ages and genders. Antibody titres decreased slightly after the 5^th week post-vaccination. The robust boosting effect of immunisation suggests that increased antibody titres following exposure to the virus may restrict viral replication, prolong the incubation period, or lessen the severity of disease.

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

Figure 1

Timing of vaccination and blood sample collection. (A) Timing of blood sampling from 103 infection-naïve health care workers (HCWs). (B) Timing of blood sampling from five previously infected HCWs. Blood was sampled from four HCWs on a weekly basis (top) and from one HCW on an hourly basis (bottom). The timing of administration of two doses of BNT162b2 mRNA vaccine is indicated by dotted lines. Arrows indicate the timing of blood collection. Blood samples were collected before the first vaccination (baseline) and just before the second vaccination (3 w). w, week; h, hour.

Figure 2

A robust boosting effect after the second vaccine dose was observed in individuals of all ages and genders. (A, C) Anti-spike (S) protein antibody titres in infection-naïve healthcare workers (n=103). The kinetics of antibody titres (U/mL) are indicated from baseline to 7 weeks after the first dose. Data by age group (A) and by gender (C) are shown. The dotted line indicates the cut-off value (0.8 U/mL). (B, D) Boosting effect before and after the second vaccine dose. The ratios of antibody titres immediately before (3 weeks) and 1 week after the second dose (4 weeks) are indicated. Data by age group (B) and by gender (D) are shown. There were no statistically significant differences in boosting effect between age groups (p = 0.25, Kruskal-Wallis test) or genders (p = 0.99, Student’s t-test). F, female; M, male.

Figure 3

Changes in antibody titres at each week post-vaccination in infection-naïve healthcare workers. (A, B) Changes in the titres of anti-spike (S) antibodies from week 1 to week 7 after the first vaccine dose by age group (A) and by gender (B). A pairwise t-test with Bonferroni correction was conducted for the multiple comparison test across the age groups. Student’s t-test was performed for statistical analyses between female (F) and male (M). The dotted line indicates the cut-off value (0.8 U/mL).

Figure 4

Robust humoral immune responses after the first dose of vaccine in previously infected healthcare workers. (A, B) Changes in antibody titres on a weekly basis (weeks 1 to 7) in previously infected healthcare workers (HCWs) (n=4) after the first dose of vaccine. Data show changes in anti-spike (S) (A) and anti-nucleocapsid (N) antibody titres (B). During the previous infection, one of the four HCWs had moderate symptoms (individual #1) and three had mild symptoms (individuals #2, 3, and 4). (C) Changes in antibody titres on an hourly basis after the first dose of vaccine in one previously infected HCW (#5). During the previous infection, this HCW had mild symptoms. The upper left figure shows a magnified view of the data from baseline to 96 hours (day 4). COI, cut-off index; h, hour; D, day. The dotted line indicates the cut-off value (0.8 U/mL for anti-S and 1.0 COI for anti-N antibodies).