A Population-Based Study of SARS-CoV-2 IgG Antibody Responses to Vaccination in Manitoba

Abstract

Understanding variables that influence antibody responses to COVID-19 vaccination within a population can provide valuable information on future vaccination strategies. In this population-based study, we examined the antibody responses to COVID-19 vaccination in Manitoba using residual serum specimens collected between January 2021 and March 2022 (n = 20,365). Samples were tested for spike and nucleocapsid IgG against SARS-CoV-2 using clinically validated assays. We assessed the impacts of multiple factors on post-vaccination antibody titres including type of vaccine, age, sex, geographic location, number of doses received, and timing of vaccination. Our investigation demonstrated that vaccination with one dose of Moderna mRNA-1273 elicited higher anti-spike IgG titres overall compared to Pfizer BNT162b2 vaccination, while one dose of Pfizer BNT162b2 followed by a second dose of Moderna mRNA-1273 exhibited higher titres than two doses of Pfizer BNT162b2 or Moderna mRNA-1273, irrespective of age. Age and time post-vaccination had considerable effects on antibody responses, with older age groups exhibiting lower anti-spike IgG titres than younger ages, and titres of those vaccinated with Pfizer BNT162b2 waning faster than those vaccinated with Moderna mRNA-1273 or a combination of Pfizer BNT162b2 and Moderna mRNA-1273. Antibody titres did not appear to be affected by sex or geographic location. Our results identify how factors such as age and type of vaccine can influence antibody responses to vaccination, and how antibody titres wane over time. This information highlights the importance of tailoring vaccine regimens to specific populations, especially those at increased risk of severe COVID-19 and can be used to inform future vaccination strategies, scheduling of booster doses, and public health measures.

Keywords: COVID-19; IgG; SARS-CoV-2; antibodies; immunity; serology; vaccines.

Figure 1

Number of COVID-19 vaccines administered by dose over time for the specimens used in this study (n = 20,365), and major changes in vaccine eligibility over time in Manitoba. Specimens were collected as part of the Manitoba COVID-19 Seroprevalence study. PCH, personal care home.

Figure 2

SARS-CoV-2 anti-spike IgG after the first and second doses of a COVID-19 vaccine. Specimens were vaccinated with either one dose of Pfizer BNT162b2 (green) or Moderna mRNA-1273 (blue), or with two doses of Pfizer BNT162b2 or Moderna mRNA-1273 or one dose of each (Pfizer/Moderna; purple). Only specimens negative for anti-nucleocapsid IgG were included. The larger dots are the mean. The smaller dots represent individual samples. The dashed line indicates a positive signal cut-off of 15 AU/mL. *** p ≤ 0.001.

Figure 3

Age differences in SARS-CoV-2 anti-spike IgG after one or two doses of a COVID-19 vaccine. Only samples negative for anti-nucleocapsid IgG were included. Specimens were vaccinated with either one dose of Pfizer BNT162b2 (green) or Moderna mRNA-1273 (blue), or with two doses of Pfizer BNT162b2 or Moderna mRNA-1273, or one dose of each (Pfizer/Moderna; purple). Dunn’s test for pairwise comparisons corrected for multiple hypothesis testing using the Benjamini–Hochberg method to compare groups. The larger dots are the mean. The smaller dots represent individual samples. The dashed line indicates a positive signal cut-off of 15 AU/mL. **** p ≤ 0.0001, *** p ≤ 0.001, * p ≤ 0.05.

Figure 4

The effect of time between vaccination and specimen collection on spike IgG responses after first and second doses of a COVID-19 vaccine. Specimens were vaccinated with either one dose of Pfizer BNT162b2 (green) or Moderna mRNA-1273 (blue), or with two doses of Pfizer BNT162b2 (green) or Moderna mRNA-1273 (blue), or one dose of each (Pfizer/Moderna; purple). For the interval between Dose 1 and specimen collection, titres were measured 14+ days after receiving the first dose and before receiving a second dose. For the interval between Dose 2 and specimen collection, titres were measured 14+ days after receiving a second dose, and before receiving a third dose. Only samples negative for anti-nucleocapsid IgG were included. The shaded regions indicate standard error intervals. The dashed line indicates a positive signal cut-off of 15 AU/mL.