Quantitative Analysis of SARS-CoV-2 Serological Responses Post Three Doses of Immunization and Prior to Breakthrough COVID-19 Infections

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.

Serological Correlates of Protection Induced by COVID-19 Vaccination in the Working Age Population: A Systematic Review and Meta-Analysis

“…Moreover, albeit based on a limited number of studies, the meta-analyses in the present investigation could suggest that titers over 1300 BAU/mL could be indicative of a degree of protective effect. Finally, although it was not possible to perform a meta-regression analysis to assess the moderating effect of age on the pooled mean antibody titer, studies that presented a higher mean age in the included sample showed a greater binding antibody concentration corresponding to protection [22,27]. This could be explained by the known association between older age and reduced vaccine efficiency, referred to as immunosenescence, which has previously been demonstrated for different vaccines [40], and that has more recently been suggested also for COVID-19 vaccines [41].…”

Serologic Response and Safety after a Third Dose of the COVID-19 BNT162b2 Vaccine in Patients with Inflammatory Bowel Diseases

“…Specifically, higher serologic response was associated with more protection from infection; in the 42.3% subjects who were infected despite receiving a third vaccine dose and being seropositive, the mounting serologic response was significantly lower than in subjects who were not infected ( Figure 3 ). Previous studies also described breakthrough infections after the booster shot, despite a serologic response above the threshold, but they did not show an association between breakthrough infection and serologic response [ 30 , 31 ]. Moreover, in our cohort, we systematically monitored SARS-CoV-2 infections by consecutive testing for anti-N antibodies and can therefore inform on the protective effect of IgG anti-S antibodies induced exclusively by the third vaccine dose without the contribution of natural infection (no hybrid immunity).…”

The Efficacy and Safety of SARS-CoV-2 Vaccinations in People with Multiple Sclerosis

“…16 "Seroconversion demonstrating an antibody response against the spike protein is the standard way of evaluating whether or not a vaccine is immunogenic," 17 said Fuller. A number of studies have demonstrated humoral responses to SARS-CoV-2 vaccines in people with MS. [18][19][20][21][22] Fuller also highlighted that antibody levels increase with subsequent booster immunisations in people with MS. 14,17,23 "That's an important consideration," continued Fuller, "especially when we're entering into an era where we still have a pandemic, but we are now able to manage and control the disease better through regular vaccination. With multiple booster immunisations, the differences between people with MS and people without in response to vaccination is going to be smaller.…”