Fig 1.
Three groups of healthcare workers (HCW) were recruited according to the timing of the second vaccine dose (black needle) at either <35 days, 35–42 days or >42 days following the first dose. Blood samples for serological tests were collected at the same timepoints from the second dose: at the time of the (pre-) second dose and at 3 weeks, 3 months and 6–9 months post-second dose. Baseline pre-first dose blood samples were available for the <35 days and >42 days groups who were recruited before the first dose, while the 35–42 days group was enrolled at the time of the second dose.
Table 1.
Baseline characteristics of participants by dosing interval.
Fig 2.
Mean titers and seropositivity rates for IgG to ancestral SARS-CoV-2 Spike and RBD by study visit and dosing interval.
Upper panel: Serum IgG titers to ancestral SARS-CoV-2 Spike and RBD measured in each group at the same time point post-2nd dose using a validated ELISA (see METHODS). Data are expressed in optical density (OD) with 95% confidence interval (CI) and fully adjusted for age, sex, education, smoking, alcohol use, body-mass index, known comorbidities (cardiovascular, neoplastic, autoimmune, renal and chronic respiratory diseases) and the number of days after 2nd vaccine dose to subsequent blood draw. The dosing interval groups 35-42-days (red symbols) and >42-days (open green symbols), were compared to the <35-days group (reference, blue closed symbols). For the summary numerical data, please refer to S3 Appendix in S1 File. Interaction terms for visit x group were all significant at p<0.0001. Therefore, between group comparisons (<35-day group as reference) were conducted with p-values *<0.05 and **<0.005. The red solid line represents the assay’s threshold of detection (see S1Appendix in S1 File for numerical values). Lower Panel: The bars represent the % of participants with seropositive IgG to ancestral SARS-CoV-2 Spike and RBD within each group by visit. Seropositivity was defined by titer levels above the assay’s threshold of detection.
Fig 3.
Mean titers and seropositivity rates for IgA to ancestral SARS-CoV-2 Spike and RBD by study visit and dosing interval.
Upper panel: Serum IgA titers to ancestral SARS-CoV-2 Spike and RBD measured in each group at the same time points post-2nd dose using a validated ELISA (see METHODS). Data are expressed in optical density (OD) with 95% confidence interval (CI) and fully adjusted for age, sex, education, smoking, alcohol use, body-mass index, known comorbidities (cardiovascular, neoplastic, autoimmune, renal and chronic respiratory diseases) and the number of days after 2nd vaccine dose to subsequent blood draw. The dosing interval groups 35-42-days (red symbols) and >42-days (open green symbols), were compared to the <35-days group (reference group, blue closed symbols). For the summary numerical data, please refer to S3 Appendix in S1 File. Interaction terms for visit x group were all significant at p<0.0001. Therefore, between group comparisons (<35-day group as reference) were conducted with p-values *<0.05 and **<0.005. The red solid line represents the assay’s threshold of detection (see S1 Appendix in S1 File for numerical values). Lower Panel: The bars represent the % of participants with seropositive IgA to ancestral SARS-CoV-2 Spike and RBD within each group by visit. Seropositivity was defined by titer levels above the assay’s threshold of detection.
Fig 4.
Mean titers and seropositivity rates for IgM to ancestral SARS-CoV-2 Spike and RBD by study visits and dosing interval groups.
Upper panel: Serum IgM titers to ancestral SARS-CoV-2 Spike and RBD measured in each group at the same time points post-2nd dose using a validated ELISA (see METHODS). Data are expressed in optical density (OD) with 95% confidence interval (CI) and fully adjusted for age, sex, education, smoking, alcohol use, body-mass index, known comorbidities (cardiovascular, neoplastic, autoimmune, renal and chronic respiratory diseases) and the number of days after 2nd vaccine dose to subsequent blood draw. The dosing interval groups were 35-42-days (red symbols) and >42-days (open green symbols), who were compared to the <35-days group (reference group, blue closed symbols). For the summary numerical data, please refer to S3 Appendix in S1 File. Interaction terms for titer levels x visit x group were all significant at p<0.0001. Therefore, between group comparisons (<35-day group as reference) were conducted with p-values *<0.05 and **<0.005. The red solid line represents the assay’s threshold of detection (see S1 Appendix in S1 File for numerical values). Lower Panel: The bars represent the % of participants with seropositive IgM to ancestral SARS-CoV-2 Spike and RBD within each group by visit. Seropositivity was defined by titer levels above the assay’s threshold of detection.
Fig 5.
Neutralizing titers to live ancestral SARS-CoV-2 and Beta variant by visits stratified by dosing interval groups.
Data are presented as logarithmic titers (means and 95% CI) needed to inhibit 50% of infection due to Ancestral or Beta variants after fully adjusted for age, sex, education, smoking, alcohol use, body-mass index, known comorbidities (cardiovascular, neoplastic, autoimmune, renal and chronic respiratory diseases) and the number of days after 2nd vaccine dose to subsequent blood draw. The dosing interval groups were 35-42-days (red symbols) and >42-days (open green symbols), who were compared to the <35-days group (reference group, blue closed symbols). For the summary numerical data, please refer to S4 Appendix in S1 File. Interaction terms for titer levels x visit x group was significant at p<0.0001. Therefore, between group comparisons (<35-day group as reference) were conducted with p-values *<0.05 and **<0.005.
Fig 6.
Anti-RBD memory B cells at 3 months according to dosing interval = <42 days or >42 days between doses.
In 30 random participants anti-RBD IgG specific B memory cells were measured using commercially available ELISPOT kit (Mabtech). Data are plotted for participants with dosing interval = <42 days (<35-days and 35-42-days groups combined) and >42-days group with the adjusted mean provided for each group. Comparison was performed using linear mixed effects model adjusted for age, sex, education, smoking, alcohol use, body-mass index, known comorbidities (cardiovascular, neoplastic, autoimmune, renal and chronic respiratory diseases) and the number of days after 2nd vaccine dose to subsequent blood draw.