Study population and setting
This was a prospective cohort study conducted in Germany that included healthcare workers who received either (1) homologous immunization with two doses, three weeks apart, of BNT162b2 (Pfizer-BioNTech) vaccine or (2) heterologous immunization with an initial dose of ChAdOx1-nCoV19 (AstraZeneca) vaccine followed 10-12 weeks later by BNT162B2. Baseline demographic data were collected at the study enrollment. Anti-nucleocapsid antigen was measured at enrollment to exclude participants with prior infection with SARS-CoV-2. B-Cell immunity against SARS-CoV-2 was quantified by measuring anti-receptor binding domain and anti-S1 antibodies using enzyme-linked immunosorbent assay (ELISA), and T-cell immunity by measuring INF-Gamma induced by S1 peptide antigen. High serum antibody avidity was defined as antibodies with more than 60% avidity. These B-cell and T-cell responses were compared between subsets of both groups, who were matched on age and sex. The proportion of participants who had local and systemic reactions after 1st (prime) and 2nd (booster) doses were captured by asking the participants to fill electric questionnaires on days 1, 3, 5, and 7 after every vaccination.
Summary of Main Findings
One hundred eighty-nine participants received two doses of BNT162B2 vaccine, three weeks apart (homologous boost group), and 110 participants received heterologous immunization with ChAdOx1 vaccine followed by BNT162B2 vaccine with a median time of 71 days between doses (heterologous boost group). The median ages of the groups were 35 and 38 years, respectively. The homologous group was 55% women vs. 78% in the heterologous group.
After vaccination with the first dose, 67% (95% CI: 57 – 76%) of those who received BNT162B2 had anti-S1 antibodies compared to 28% (95% CI: 18 – 40%) in the ChAdOx1 group, with a statistically significant difference. However, after the second dose with BNT162b2, all patients had anti-SARS-COV-2 S1 antibodies. Similarly, after the first dose, 95% of the homologous group had neutralizing antibodies compared to 84% in the heterologous group, with a statistically significant difference, but 100% and 99% had neutralizing antibodies after the second dose, respectively.
High serum antibody avidity was not detected after the first dose of vaccine in either group. Avidity is the overall strength of connection between an antibody and its attachment site on a disease-causing microbe. After the second dose, high serum antibody avidity was detected in 100% (95% CI: 94 – 100%) of participants in the heterologous group and 90% (95% CI 74 – 97%) in the homologous group. The median level for the interferon gamma assay was statistically higher in the heterologous group (2.25 AU) than the homologous group (1.67 AU). Across groups, there were no noticeable differences in local reactions to either the first or second dose of vaccine. However, systemic reactions were more common after the first dose of ChAdOx1 in the heterologous group vs. the first dose of BNT162b2 in the homologous group, but less common after the second dose in the heterologous group.
B-cell and T-cell immune response were measured in subsets in both groups who were matched on age and sex and at comparable intervals following vaccine administration in both groups, which strengthen the comparability between the study groups. Also, data were collected prospectively which minimized the chance of information or recall bias.
Only subsets of both cohorts had serum testing for B-cell and T-cell immune responses, and matching between both cohorts were based only on age and sex. This could have resulted in selection bias if subjects in both groups were different in a way that that could affect their immune response to the vaccine (e.g., being immunocompromised). Also, local and systemic reactions were measured by soliciting response through direct questionnaires instead of observation. Since the study was unmasked as well, participants might have been influenced to be more or less observant to their reactions, based on their prior knowledge of their specific vaccine’s side effects. Furthermore, there was not a comparison group consisting of heterologous immunization with a 3-week interval between doses, which makes it difficult to discern whether the heterologous immunization or difference in timing was responsible for these results.
This is the first study to examine B-cell and T-cell immune responses as well as local and systematic reactions between heterologous (ChAdOx1 then BNT162b2) and homologous (BNT162b2 for both doses) immunization groups. Since females have been reported to be more prone to rare but serious thromboembolic events following ChAdOx1 vaccination, this study provides strong laboratory data for the efficacy and safety of heterologous immunization, at least at the short run.