Comparison of IgA, IgG, and Neutralizing Antibody Responses Following Immunization With Moderna, BioNTech, AstraZeneca, Sputnik-V, Johnson and Johnson, and Sinopharm's COVID-19 Vaccines

Abstract

In an ongoing multinational trial, we obtained blood samples from 365 volunteers vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from Sinopharm. After collecting reactogenicity data, the expression of S-Protein binding IgG and IgA was analyzed using an automated sandwich ELISA system. Serum neutralizing potentials were then investigated using an ACE-2-RBD neutralizing assay. Moderna's vaccine induced the highest amounts of SARS-CoV-2 specific neutralizing antibodies compared to the other groups. In contrast, Sinopharm and Johnson and Johnson's vaccinees presented the lowest SARS-CoV-2-specific antibody titers. Interestingly, moderate to high negative correlations between age and virus-specific IgG expression were observed in the Johnson and Johnson (ρ =-0.3936) and Sinopharm (ρ =-0.6977) groups according to Spearman's rank correlation analysis. A negative correlation was seen between age and IgA expression in the Sputnik-V group (ρ =-0.3917). The analysis of virus neutralization potentials in age categories demonstrated that no significant neutralization potential was observed in older vaccinees (61and 80 years old) in the Sputnik-V Johnson and Johnson and Sinopharm vaccinees' groups. In contrast, neutralization potentials in sera of Moderna, BioNTech, and AstraZeneca vaccinees were statistically comparable in all age categories. Furthermore, while the AstraZeneca vaccine alone induced moderate IgG and IgA expression, the combination with Moderna or BioNTech mRNA vaccines induced significantly higher antibody levels than a double dose of AstraZeneca and similar IgG expression and neutralization potential compared to Moderna or BioNTech vaccines used alone. These results suggest that mRNA vaccines are the most immunogenic after two doses. DNA vectored vaccines from AstraZeneca and Sputnik-V presented lower but significant antibody expression and virus neutralizing properties after two doses. The lowest antibody and neutralization potential were observed in the Sinopharm or Johnson and Johnson vaccinees. Especially elderly over 60 presented no significant increase in neutralizing antibodies after vaccination. The data also indicate that heterologous vaccination strategies combining the AstraZeneca DNA vectored vaccines and mRNA vaccines are more effective in the induction of neutralizing antibodies compared to their homologous counterparts.

Keywords: COVID-19 vaccines; ELISA; IgA; IgG; SARS-CoV-2; neutralizing antibodies.

Figure 1

Level of reported systemic adverse reactions. Graphs represent the proportion of individuals presenting side effects in Moderna (A), BioNTech (B), AstraZeneca (C), Johnson and Johnson (D), Sputnik-V (E), and Sinopharm (F) vaccinees. The white parts of the histograms indicate the percentage of persons with no systemic side effects. The grey portions represent the percentage of people with mild side effects, while the dark parts indicate the percentages of individuals with severe side effects.

Figure 2

Higher expression of SARS-CoV-2 reactive IgG and IgA after immunization mRNA vaccines. Graphs represent the expression SARS-CoV-2 spike-protein binding IgG (A) and IgA (B) in arbitrary binding units (ABU). Each symbol represents individual donors. Indicated p values were calculated using the Kruskal-Wallis test followed by Dunnett’s post hoc to compare each group to the controls before vaccination. Bars represent the median antibody expression in each group. Significance is accepted if p <0.05.

Figure 3

Higher neutralizing potential of mRNA vaccines in mRNA-vaccinated individuals. The graph represents the relative neutralizing antibody expression observed using sera from each vaccination group. Each symbol represents individual donors. Indicated p values were calculated using Kruskal-Wallis ‘test followed by Dunn’s comparison post hoc to compare all groups. Bars represent the mean ± SEM percentage of relative neutralizing antibody expression in each group. Significance is accepted if p <0.05.

Figure 4

Strong age-dependent decrease of vaccine-induced antibody decrease in Sputnik-V, Johnson and Johnson, and Sinopharm vaccinees. Graphs represent the correlation of SARS-CoV-2 specific spike-protein binding IgG and IgA with age in Moderna (A, B), BioNTech (C, D), AstraZeneca (E, F), Sputnik-V (G, H), Johnson and Johnson (I, J), and Sinopharm (K, L) vaccinees. Dots represent individual donors. Indicated r values were calculated using Spearman’s rank-order analysis.

Figure 5

Low neutralizing antibody response in older vaccinees of Sputnik-V, Johnson and Johnson, and Sinopharm groups. Graphs represent the relative expression of neutralizing antibodies observed using sera from Sputnik-V (A), Johnson and Johnson (B), Sinopharm (C), Moderna (D), BioNTech (E), and AstraZeneca (F) vaccinees in 3 different age categories: 18-40, 41-60, and 61-80+ years old. Each symbol represents individual donors. Indicated p values were calculated using Kruskal-Wallis ‘test followed by Dunn’s comparison post hoc to compare all groups. Bars represent the mean percentages of relative neutralizing antibody expression ± SEM. Significance is accepted if p <0.05.

Figure 6

High neutralizing antibody expression in AstraZeneca- mRNA vaccine combinations. Graphs represent the expression of SARS-CoV-2 specific spike-protein binding IgG (A), IgA (B), and neutralizing antibody expression (C) observed in the sera of people that received homologous (AstraZeneca, Moderna, or BioNTech) ‘s COVID-19 vaccines or heterologous vaccine doses (AstraZeneca-Moderna or AstraZeneca-BioNTech). Each symbol represents individual donors. Indicated p values were calculated using Kruskal-Wallis ‘test followed by Dunn’s comparison post hoc to compare all groups. Bars represent the median (A, B) of SARS-CoV-2 spike protein-specific antibody expression in each group in arbitrary binding units (ABU) or the means ± SEM percentages of relative neutralizing antibody expression (C). Significance is accepted if p <0.05.