Analysis of immunization time, amplitude, and adverse events of seven different vaccines against SARS-CoV-2 across four different countries

Maria Elena Romero-Ibarguengoitia, Arnulfo González-Cantú, Chiara Pozzi, Riccardo Levi, Maximiliano Mollura, Riccardo Sarti, Miguel Ángel Sanz-Sánchez, Diego Rivera-Salinas, Yodira Guadalupe Hernández-Ruíz, Ana Gabriela Armendariz-Vázquez, Gerardo Francisco Del Rio-Parra, Irene Antonieta Barco-Flores, Rosalinda González-Facio, Elena Azzolini, Riccardo Barbieri, Alessandro Rodrigo de Azevedo Dias, Milton Henriques Guimarães Júnior, Alessandra Bastos-Borges, Cecilia Acciardi, Graciela Paez-Bo, Mauro Martins Teixeira, Maria Rescigno, Maria Elena Romero-Ibarguengoitia, Arnulfo González-Cantú, Chiara Pozzi, Riccardo Levi, Maximiliano Mollura, Riccardo Sarti, Miguel Ángel Sanz-Sánchez, Diego Rivera-Salinas, Yodira Guadalupe Hernández-Ruíz, Ana Gabriela Armendariz-Vázquez, Gerardo Francisco Del Rio-Parra, Irene Antonieta Barco-Flores, Rosalinda González-Facio, Elena Azzolini, Riccardo Barbieri, Alessandro Rodrigo de Azevedo Dias, Milton Henriques Guimarães Júnior, Alessandra Bastos-Borges, Cecilia Acciardi, Graciela Paez-Bo, Mauro Martins Teixeira, Maria Rescigno

Abstract

Background: Scarce information exists in relation to the comparison of seroconversion and adverse events following immunization (AEFI) with different SARS-CoV-2 vaccines. Our aim was to correlate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI.

Methods: A multicentric comparative study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured at baseline, 21-28 days after the first and second dose (when applicable) of the following vaccines: BNT162b2 mRNA, mRNA-1273, Gam-COVID-Vac, Coronavac, ChAdOx1-S, Ad5-nCoV and Ad26.COV2. Mixed model and Poisson generalized linear models were performed.

Results: We recruited 1867 individuals [52 (SD 16.8) years old, 52% men]. All vaccines enhanced anti-S1 and anti-S2 IgG antibodies over time (p<0.01). The highest increase after the first and second dose was observed in mRNA-1273 (p<0.001). There was an effect of previous SARS-CoV-2 infection; and an interaction of age with previous SARS-CoV-2 infection, Gam-COVID-Vac and ChAdOx1-S (p<0.01). There was a negative correlation of Severe or Systemic AEFI (AEs) of naïve SARS-CoV-2 subjects with age and sex (p<0.001); a positive interaction between the delta of antibodies with Gam-COVID-Vac (p=0.002). Coronavac, Gam-COVID-Vac and ChAdOx1-S had less AEs compared to BNT162b (p<0.01). mRNA-1273 had the highest number of AEFIs. The delta of the antibodies showed an association with AEFIs in previously infected individuals (p<0.001).

Conclusions: The magnitude of seroconversion is predicted by age, vaccine type and SARS-CoV-2 exposure. AEs are correlated with age, sex, and vaccine type. The delta of the antibody response only correlates with AEs in patients previously exposed to SARS-CoV-2.

Registration number: ClinicalTrials.gov, identifier NCT05228912.

Keywords: COVID-19; SARS-CoV-2; immunization; seroconversion; vaccines.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Romero-Ibarguengoitia, González-Cantú, Pozzi, Levi, Mollura, Sarti, Sanz-Sánchez, Rivera-Salinas, Hernández-Ruíz, Armendariz-Vázquez, Del Rio-Parra, Barco-Flores, González-Facio, Azzolini, Barbieri, de Azevedo Dias, Henriques Guimarães Júnior, Bastos-Borges, Acciardi, Paez-Bo, Teixeira and Rescigno.

Figures

Figure 1
Figure 1
IgG antibody levels by vaccine. IgG antibody response was measured in serum of naïve and SARS-CoV-2 previously exposed (SARS-CoV-2 Exp) subjects at different time points (T0, T1 and T2) and vaccinated with different vaccine types. Samples ≥ 15 AU/mL were considered positive. Log scale on y axis. The box plots show the interquartile range, the horizontal lines show the median values, and the whiskers indicate the minimum-to-maximum range. Each dot corresponds to an individual subject. P-values were determined using 2-tailed Kruskal-Wallis test with Dunn’s multiple comparisons test. P-values refer to baseline (T0) when there are no connecting lines. ns, not significant.
Figure 2
Figure 2
Antibody titers classified by age type of vaccine and Time. Figure shows change in antibody concentration through age, divided SARS-CoV-2 history, and vaccine type. Antibodies are expressed in logarithm and age has a Z distribution.
Figure 3
Figure 3
Percentage of systemic or severe adverse events after the second dose, stratified by vaccine. The graph shows the frequency of appearance of each systemic or severe adverse event across the considered vaccine groups.
Figure 4
Figure 4
Forest plot for the GLM Poisson model coefficients stratified by SARS-CoV-2 history. Women and young individuals developed more severe or systemic AEFI (AEs). There was no effect of Body Mass Index. In the naïve SARS-CoV-2 cohort, the vaccines Gam-COVID-Vac, Coronavac and ChAdOx1-S were related to fewer AEs after the second dose than BNT162b mRNA. However, for naïve SARS-CoV-2 patients who received Gam-COVID-Vac, higher antibody levels after the second dose were related to a greater number of AEs. In people previously exposed to SARS-CoV-2, those receiving Gam-COVID-Vac showed a greater number of AEs compared to BNT162b mRNA, while subjects receiving Coronavac showed significantly fewer events when compared to BNT162b mRNA.

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