ABSTRACT
BACKGROUND: Vaccine mediated SARS-CoV-2 antibody responses should be carefully evaluated. With regular follow-up in healthy individuals, we aimed to determine SARS-CoV-2 serological responses post three doses of immunization and prior to breakthrough infections in the Canadian population. METHODS: In a prospective cohort study, we enrolled 140 healthy participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor-binding domain were quantified by immunoassay post three doses of immunization. With COVID-19 rapid antigen test, polymerase chain reaction, and whole genome sequencing, 27 breakthrough infections were identified. RESULTS: Following SARS-CoV-2 vaccine (including BNT162b2, AZD1222, and mRNA-1273), the median serum anti-spike protein antibody level was 143.6 BAU/mL (binding antibody unit, interquartile range 79.0-266.6) post the first dose of immunization, 1046.4 BAU/mL (423.9-1738.2) post the second dose, and 1604.7 BAU/mL (700.1-3764.0) post the third dose. Observed differences were significant (p ≤ 0.001). The median antibody level of 1604.7 BAU/mL post third dose is 45.6 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In seven breakthrough cases characterized by whole genome sequencing, prior to infection, antibody concentrations of breakthrough cases were at 3249.4 (Delta), 2748.4 (Delta), 4893.9 (Omicron), 209.1 (Omicron), and 231.5 (Omicron), 725.7 (Omicron), and 2346.6 (Omicron) BAU/mL. Compared with the average antibody concentration of 2057.7 BAU/mL (58 times that of the seroconversion concentration) from above seven cases, 37.2% of triple vaccinated, 19.0% of double vaccinated, and 1.5% single dosed individuals have higher SARS-CoV-2 antibody levels. CONCLUSIONS: Most vaccines are effective in producing robust antibody responses when more than one dose is given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants have SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.
ABSTRACT
(1) Background: COVID-19 vaccine effectiveness should be carefully evaluated and explicitly defined. To our knowledge, this is the first report to quantitatively evaluate humoral responses post 3 doses of SARS-CoV-2 immunization and prior to breakthrough COVID-19 infection in Canadian cancer patients. (2) Methods: In a prospective cohort study, we enrolled 185 cancer participants post COVID-19 vaccination in Kingston, Ontario, Canada. IgG antibodies against the SARS-CoV-2 spike receptor-binding domain were quantified by immunoassay post three doses of immunization. With the COVID-19 rapid antigen test and polymerase chain reaction (PCR), 16 breakthrough infections were identified. Results: Following SARS-CoV-2 vaccination (including BNT162b2, AZD1222, and mRNA-1273), the mean serum anti-spike protein antibody level was 197.2 BAU/mL (binding antibody unit, SD ± 393.9), 1335.9 BAU/mL (±3337.8), and 3164.8 BAU/mL (±6500.9) post the first, second, and third dose of vaccination. Observed differences were significant (p ≤ 0.001). The average antibody level of 3164.8 BAU/mL post the third dose was 89.9 times that of the seroconversion level (35.2 BAU/mL). This indicates that most vaccines approved are effective in producing robust antibody responses. In 11 breakthrough cases confirmed by PCR, prior to infection, the average antibody concentration was 3675.6 BAU/mL with the highest concentration being 9107.4 BAU/mL. Compared with this average antibody concentration of 3675.6 BAU/mL (104.4 times that of the seroconversion concentration), 0% of single dosed, 9.6% of double vaccinated, and 29.5% of triple vaccinated cancer patients had higher SARS-CoV-2 antibody levels. When patients were split into hematological and solid cancer, the hematological cancer group demonstrated lower serological responses than the solid cancer group in the first and second doses (first dose, average concentration 11.1 vs. 201.4 BAU/mL, respectively, p < 0.05; second dose, average concentration 441.5 vs. 1725.9 BAU/mL, respectively, p < 0.05). There was no difference in the third dose level (1756.3 vs. 2548.0 BAU/mL, p = 0.21). (4) Conclusions: Most vaccines were effective in producing robust antibody responses when more than one dose was given, and the more doses the higher the serological response. Likely due to the highly contagious nature of SARS-CoV-2 variants, a significant number of participants had SARS-CoV-2 antibody responses lower than the average antibody concentration prior to the known breakthrough infections. Additional vaccination is likely required to ensure immunity against infection by SARS-CoV-2.
