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. 2022 May 27;10(6):858.
doi: 10.3390/vaccines10060858.

Comparison of BNT162b2-, mRNA-1273- and Ad26.COV2.S-Elicited IgG and Neutralizing Titers against SARS-CoV-2 and Its Variants

Nigam H Padhiar  1 , Jin-Biao Liu  1 , Xu Wang  1   2 , Xiao-Long Wang  1 , Brittany H Bodnar  1   3 , Shazheb Khan  1 , Peng Wang  1 , Adil I Khan  1 , Jin-Jun Luo  4 , Wen-Hui Hu  1   2 , Wen-Zhe Ho  1   2   5
Affiliations

Comparison of BNT162b2-, mRNA-1273- and Ad26.COV2.S-Elicited IgG and Neutralizing Titers against SARS-CoV-2 and Its Variants

Nigam H Padhiar et al. Vaccines (Basel). .

Abstract

Because the vaccine-elicited antibody and neutralizing activity against spike protein of SARS-CoV-2 are associated with protection from COVID-19, it is important to determine the levels of specific IgG and neutralization titers against SARS-CoV-2 elicited by the vaccines. While three widely used vaccine brands (Pfizer-BNT162b2, Moderna-mRNA-1273 and Johnson-Ad26.COV2.S) are effective in preventing SARS-CoV-2 infection and alleviating COVID-19 illness, they have different efficacy against COVID-19. It is unclear whether the differences are due to varying ability of the vaccines to elicit a specific IgG antibody response and neutralization activity against spike protein of the virus. In this study, we compared the plasma IgG and neutralization titers against spike proteins of wild-type SARS-CoV-2 and eight variants in healthy subjects who received the mRNA-1273, BNT162b2 or Ad26.COV2.S vaccine. We demonstrated that subjects vaccinated with Ad26.COV2.S vaccine had significantly lower levels of IgG and neutralizing titers as compared to those who received the mRNA vaccines. While the linear regression analysis showed a positive correlation between IgG levels and neutralizing activities against SARS-CoV-2 WT and the variants, there was an overall reduction in neutralizing titers against the variants in subjects across the three groups. These findings suggest that people who received one dose of Ad26.COV2.S vaccine have a more limited IgG response and lower neutralization activity against SARS-CoV-2 WT and its variants than recipients of the mRNA vaccines. Thus, monitoring the plasma or serum levels of anti-SARS-CoV-2 spike IgG titer and neutralization activity is necessary for the selection of suitable vaccines, vaccine dosage and regimens.

Keywords: Ad26.COV2.S; BNT162b2; SARS-CoV-2; antibody; mRNA-1273; neutralization; vaccine; variants.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of specific anti-SARS-CoV-2 S1 IgG in plasma from vaccine recipients and distribution of ID50 values for SARS-CoV-2 WT. IgG titers and relative frequency for three vaccine groups (n = 10 for Ad26COV2.S, n = 26 for mRNA-1273 and n = 48 for BNT162b2). (A) Plasma anti-spike IgG titer comparison. Individual IgG titers in plasma collected from the vaccines are determined by ELISA assay and plotted for each vaccine group. A Kruskal–Wallis one-way ANOVA with Dunn’s Multiple comparisons test (comparing each column to every other column) was used to evaluate for statistical significance, which is defined as follows: *** (p ≤ 0.001). The numbers above asterisk indicate fold changes of IgG titers between two groups (the pairwise comparisons). (B) IgG titer frequency. Anti-spike IgG titers are depicted in 30,000 ng/mL intervals. The numbers on the top of each bar are the percentage of subjects whose IgG titers fall within the range shown on the abscissa axis. (C) Neutralizing ID50 values distribution of each vaccine group against SARS-CoV-2 WT. The numbers on the top of each bar are the percentage of subjects whose neutralizing ID50 titers fall within the range shown on the abscissa axis. GraphPad Prism version 9.1.1 was used for all statistical analysis for this figure.
Figure 2
Figure 2
Inter-vaccine comparison of ID50 values for each variant. Plasma obtained from mRNA-1273-, BNT162b2- or Ad26.COV2.S-vaccinated subjects were collected. Neutralization was measured with recombinant vesicular stomatitis virus (rVSV)-based pseudovirus-bearing spike proteins of SARS-CoV-2 WT or the variants. The reciprocal neutralizing titers at a 50% inhibitory dilution (ID50, units = 1/dilution) against each SARS-CoV-2 variant are calculated for each donor and plotted in figure to compare among vaccine groups. A Kruskal–Wallis one-way ANOVA with Dunn’s Multiple comparisons test (comparing each column to every other column) was used to evaluate for statistical significance, which is defined as follows: ns (p > 0.05), * (p ≤ 0.05), ** (p ≤ 0.01), and *** (p ≤ 0.001). The numbers above asterisks indicate fold changes of geometric mean ID50 values between two groups (the pairwise comparisons). GraphPad Prism version 9.1.1 was used for all statistical analysis for this figure.
Figure 3
Figure 3
Neutralizing ID50 values for WT vs. variants in all three vaccine groups. Plasma obtained from mRNA-1273-, BNT162b2- or Ad26.COV2.S-vaccinated subjects were collected. Neutralization was measured with recombinant vesicular stomatitis virus (rVSV)-based pseudovirus-bearing spike proteins of SARS-CoV-2 WT or the variants. The reciprocal neutralizing titers at a 50% inhibitory dilution (ID50, units = 1/dilution) against each SARS-CoV-2 variant are calculated for each donor and plotted on figure to compare between SARS-CoV-2 WT and each variant. Friedman one-way ANOVA with Dunn’s multiple comparisons test (all variants compared to WT) was used to evaluate for statistical significance, which is defined as follows: ns (p > 0.05), * (p ≤ 0.05), ** (p ≤ 0.01), *** (p ≤ 0.001), and **** (p ≤ 0.0001). The fold changes in geometric mean ID50 values between two groups (the pairwise comparisons), as well as 95% CI for the fold change are shown above asterisk. The dots in figures indicate the ID50 titers of vaccinated individuals. GraphPad Prism version 9.1.1 in conjunction with Python version 3.8.8 was used for all statistical analysis for this figure.
Figure 4
Figure 4
Linear regression for IgG titers vs. neutralizing ID50 values for WT SARS-CoV-2 and its variants. Shown is the correlation of the neutralizing titers ID50 (ordinate) and anti-SARS-CoV-2 spike S1 IgG levels (abscissa) of plasma from vaccinated subjects (n = 84 for vaccine group). Each figure contains the coefficient of determination (R2) as well as the slope (m). Significance was evaluated by calculating p values, which tests the null hypothesis that the slope is zero (no correlation). Linear regression analysis was performed using GraphPad Prism 9.1.1. software. Pearson’s correlation coefficients were calculated. Simple linear regression (solid line) is shown. R2 = goodness of fit. p-values less than 0.05 are statistically significant. All p values in each regression plot are <0.05.
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