Dynamics of Different Classes and Subclasses of Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Variants after Coronavirus Disease 2019 and CoronaVac Vaccination in Thailand

Abstract

The humoral immune response plays a key role in protecting the population from SARS-CoV-2 transmission. Patients who recovered from COVID-19 as well as fully vaccinated individuals have elevated levels of antibodies. The dynamic levels of the classes and subclasses of antibody responses to new variants that occur in different populations remain unclear. We prospectively recruited 60 participants, including COVID-19 patients and CoronaVac-vaccinated individuals, in Thailand from May to August 2021. Plasma samples were collected on day 0, day 14, and day 28 to determine the dynamic levels of the classes and subclasses of plasma antibodies against the receptor-binding domain (RBD) in the spike protein (S) of four SARS-CoV-2 strains (Wuhan, Alpha, Delta, and Omicron) via enzyme-linked immunosorbent assay. Our results indicated that the patients with SARS-CoV-2 infections had broader class and subclass profiles as well as higher levels of anti-S RBD antibodies to the Wuhan, Alpha, and Delta strains than did the CoronaVac-vaccinated individuals. The median antibody levels increased and subsequently declined in a month in the COVID-19 patients and in the vaccinated group. Correlations of the classes and subclasses of antibodies were observed in the COVID-19 patients but not in the vaccinated individuals. The levels of all of the anti-S RBD antibodies against the Omicron variant were low in the patients and in the vaccinated individuals. Our study revealed distinct antibody profiles between the two cohorts, suggesting different pathways of immune activation. This could have an impact on protection from infections by new variants of concern (VOC). IMPORTANCE The antibody responses to new SARS-CoV-2 variants that occur in different populations remain unclear. In this study, we recruited 60 participants, including COVID-19 patients and CoronaVac-vaccinated individuals, in Thailand and determined the dynamic levels of the IgG, IgA, IgM, and IgG subclasses of antibodies against the spike protein (S) of four SARS-CoV-2 strains. Our results showed that the patients with SARS-CoV-2 infections had broader profiles and higher levels of antibodies to the Wuhan, Alpha, and Delta strains than did the CoronaVac-vaccinated individuals. The antibody levels of both groups increased and subsequently decreased within 1 month. Higher and functional correlations of these antibodies were observed in the COVID-19 patients. The levels of all anti-S RBD antibodies against the Omicron variant were low in patients and vaccinated individuals. Our study revealed distinct antibody responses between the two groups, suggesting different pathways of immune response, which may have an impact on protection from infections by new SARS-CoV-2 variants.

Keywords: COVID-19; IgA; IgG; IgM; SARS-CoV-2; antibodies; antibody; coronavirus variants; plasma antibody; vaccine; vaccines.

FIG 1

Levels of IgM, IgA, and IgG antibodies against the S RBD protein of SARS-CoV-2 variants in COVID-19 patients (A, C, and E) and in vaccinated individuals (B, D, and F) at different time points. Antibodies were determined by ELISA from the plasma samples of patients at the time of diagnosis (day 0) (n = 30), day 14 (n = 13), and day 28 (n = 22) as well as from the plasma samples of vaccinated individuals prior to vaccination (day 0) (n = 30), day 14 (n = 30) and day 28 (n = 30) after the second dose of vaccination. (A and B) IgM level, (C and D) IgA level, and (E and F) IgG level. The Mann-Whitney test was used to compare the median differences between groups.

FIG 2

Levels of IgG subclasses of antibody response to the S RBD protein of SARS-CoV-2 variants in COVID-19 patients (A, C, E, and G) and vaccinated individuals (B, D, F, and H). Antibodies were determined from the plasma samples of patients at the time of diagnosis (day 0) (n = 30), day 14 (n = 13), and day 28 (n = 22) as well as from the plasma samples of vaccinated individuals prior to vaccination (day 0) (n = 30), day 14 (n = 30), and day 28 (n = 30) after the second dose of vaccination. (A and B) IgG1 level, (C and D) IgG2 level, (E and F) IgG3 level, and (G and H) IgG4 level. The Mann-Whitney test was used to compare the median differences between groups.

FIG 3

Correlation between the IgA and IgG antibody levels to S SARS-CoV-2 Wuhan and variants on day 14 (A–H) and day 28 (I–P) in COVID-19 patients and in CoronaVac-vaccinated individuals. (A, E, I, and M) IgA versus IgG antibody against the Wuhan strain. (B, F, J, and N) IgA versus IgG antibody against the Alpha variant. (C, G, K, and O) IgA versus IgG antibody against the Delta variant. (D, H, L, and P) IgA versus IgG antibody against the Omicron variant. Antibodies were determined from the plasma samples of COVID-19 patients on day 14 (n = 13), day 28 (n = 22) as well as from the plasma samples of vaccinated individuals on day 14 (n = 30) and day 28 (n = 30). The pairwise correlation coefficient (ρ) was determined using Spearman’s rank correlation.

FIG 4

Correlation between IgG1 and IgG3 antibody levels to S SARS-CoV-2 Wuhan and variants on day 14 (A–H) and day 28 (I–P) in COVID-19 patients and in CoronaVac-vaccinated individuals. (A, E, I, and M) IgG1 versus IgG3 antibody against the Wuhan strain. (B, F, J, and N) IgG1 versus IgG3 antibody against the Alpha variant. (C, G, K, and O) IgG1 versus IgG3 antibody against the Delta variant. (D, H, L, and P) IgG1 versus IgG3 antibody against the Omicron variant. Antibodies were determined from the plasma samples of COVID-19 patients on day 14 (n = 13), day 28 (n = 22) as well as from the plasma samples of vaccinated individuals on day 14 (n = 30) and day 28 (n = 30). The pairwise correlation coefficient (ρ) was determined using Spearman’s rank correlation.

FIG 5

Seropositivity of different classes and IgG subclasses of anti-S RBD antibodies of SARS-CoV-2 variants in COVID-19 patients and in vaccinated individuals. The antibody levels were determined in plasma samples by ELISA. The patients were enrolled at the time of diagnosis (day 0), and blood was collected on day 0 (n = 30), day 14 (n = 13), and day 28 (n = 22). The vaccinated individuals were enrolled before vaccination (day 0) (n = 30). Blood samples were obtained on day 14 (n = 30) and day 28 (n = 30) after the second dose of vaccination. A high positive rate is shown in red, whereas a low positive rate is shown in green. Yellow, orange, and red for each block represent positive rates of antibody at 5.55, 8.91, 23.76, 6.57, 6.51, 11.08, and 8.57 U/mL for IgM, IgA, IgG, IgG1, IgG2, IgG3, and IgG4, respectively.

FIG 6

Neutralizing antibody (% inhibition) against the S SARS-CoV-2 Wuhan strain and Omicron variant in COVID-19 patients (n = 13) and in CoronaVac-vaccinated individuals (n = 30). The antibody levels were determined in plasma samples collected on day 14 using a cPass kit. A percent inhibition of <30 was interpreted as negative.

FIG 7

Correlation between neutralizing antibodies (% inhibition) and S RBD specific antibodies on day 14 against the Wuhan strain (A–D, I–L) and Omicron variant (E–H, M–P) in COVID-19 patients (n = 13) (A–H) and in CoronaVac-vaccinated individuals (n = 30) (I–P). (A, E, I, and M) Neutralizing antibody versus IgA antibody. (B, F, J, and N) Neutralizing antibody versus IgG antibody. (C, G, K, and O) Neutralizing antibody versus IgG1 antibody. (D, H, L and P) Neutralizing antibody versus IgG3 antibody. The pairwise correlation coefficient (ρ) was determined using Spearman’s rank correlation.