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. 2023 Nov 7;11(11):1694.
doi: 10.3390/vaccines11111694.

Antibody Profiling of Microbial Antigens in the Blood of COVID-19 mRNA Vaccine Recipients Using Microbial Protein Microarrays

Hiroaki Saito  1   2 , Hiroki Yoshimura  1   3 , Makoto Yoshida  1   4 , Yuta Tani  5   6 , Moe Kawashima  1 , Taiga Uchiyama  1 , Tianchen Zhao  1 , Chika Yamamoto  1 , Yurie Kobashi  1   7 , Toyoaki Sawano  1 , Seiya Imoto  8 , Hyeongki Park  9 , Naotoshi Nakamura  9 , Shingo Iwami  9 , Yudai Kaneko  10   11 , Aya Nakayama  12 , Tatsuhiko Kodama  11 , Masatoshi Wakui  6 , Takeshi Kawamura  11   12 , Masaharu Tsubokura  1   2   7   13
Affiliations

Antibody Profiling of Microbial Antigens in the Blood of COVID-19 mRNA Vaccine Recipients Using Microbial Protein Microarrays

Hiroaki Saito et al. Vaccines (Basel). .

Abstract

Although studies have demonstrated that infections with various viruses, bacteria, and parasites can modulate the immune system, no study has investigated changes in antibodies against microbial antigens after the COVID-19 mRNA vaccination. IgG antibodies against microbial antigens in the blood of vaccinees were comprehensively analyzed using microbial protein microarrays that carried approximately 5000 microbe-derived proteins. Changes in antibodies against microbial antigens were scrutinized in healthy participants enrolled in the Fukushima Vaccination Community Survey conducted in Fukushima Prefecture, Japan, after their second and third COVID-19 mRNA vaccinations. Antibody profiling of six groups stratified by antibody titer and the remaining neutralizing antibodies was also performed to study the dynamics of neutralizing antibodies against SARS-CoV-2 and the changes in antibodies against microbial antigens. The results showed that changes in antibodies against microbial antigens other than SARS-CoV-2 antigens were extremely limited after COVID-19 vaccination. In addition, antibodies against a staphylococcal complement inhibitor have been identified as microbial antigens that are associated with increased levels of neutralizing antibodies against SARS-CoV-2. These antibodies may be a predictor of the maintenance of neutralizing antibodies following the administration of a COVID-19 mRNA vaccine.

Keywords: COVID-19; antibody; bacteria; vaccine.

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Conflict of interest statement

Yudai Kaneko is employed by the company Medical & Biological Laboratories, Co., Ltd., Tokyo, Japan. MBL imported the testing material used in this research. Yurie Kobashi and Masaharu Tsubokura received a research grant from the Pfizer Health Research Foundation for research not associated with this work. Masaharu Tsubokura received a research grant from Moderna Inc. outside of this work. The remaining authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1
(a) Number of antibodies against microbial antigens. Number of antibodies against microbial antigens, excluding SARS-CoV-2 antigens, in sera collected three times (1st, 2nd, and 3rd represent the first, second, and third blood sample collections, respectively) after the second vaccination and once (4th represents the fourth blood collection) after the third vaccination from eight individuals. (b) Changes in the level of antibodies against spike proteins in various mutant strains of SARS-CoV-2 over time. In the Table, 1, 2, 3, and 4 represent the first, second, third, and fourth blood sample collections, respectively. The fluorescence intensity ratios of relative values against the negative controls are indicated as relative log2 ratios and represented by the red intensity in the figure. (c) Changes in the level of antibodies against SARS-CoV spike proteins over time. (d) Changes in the level of antibodies against human coronavirus spike proteins over time. (e) Changes in the level of antibodies against human adenovirus D spike proteins over time.
Figure 1
Figure 1
(a) Number of antibodies against microbial antigens. Number of antibodies against microbial antigens, excluding SARS-CoV-2 antigens, in sera collected three times (1st, 2nd, and 3rd represent the first, second, and third blood sample collections, respectively) after the second vaccination and once (4th represents the fourth blood collection) after the third vaccination from eight individuals. (b) Changes in the level of antibodies against spike proteins in various mutant strains of SARS-CoV-2 over time. In the Table, 1, 2, 3, and 4 represent the first, second, third, and fourth blood sample collections, respectively. The fluorescence intensity ratios of relative values against the negative controls are indicated as relative log2 ratios and represented by the red intensity in the figure. (c) Changes in the level of antibodies against SARS-CoV spike proteins over time. (d) Changes in the level of antibodies against human coronavirus spike proteins over time. (e) Changes in the level of antibodies against human adenovirus D spike proteins over time.
Figure 2
Figure 2
(a) Number of antibodies against microbial antigens, excluding antibodies against SARS-CoV-2, in the sera of six groups stratified by antibody titer and the remaining neutralizing antibodies. The cross mark represents the mean while the box represents the median, 25th percentile, and 75th percentile. The upper and lower bars represent the minimum and maximum values. (b) The level of antibodies against spike proteins in various mutant strains of SARS-CoV-2. The fluorescence intensity ratios of the relative values against the negative controls are indicated as relative log2 ratios and are represented by the red intensity in the figure. (c) Shapley additive explanation (SHAP) values of antibodies against each microbial antigen, indicating their level of importance. The 10 antigens are shown in order of their SHAP values. * Victoria strain; § Tokio strain; † HPV-77 strain, BR2S antigen; ‡ HPV-77 strain, K2S antigen. (d) Relationship between the SHAP value and the feature value of antibodies against each microbial antigen. The feature value of a dot is positively correlated with high (red) and negatively correlated with low (blue) values. * Victoria strain; § Tokio strain; † HPV-77 strain, BR2S antigen; ‡ HPV-77 strain, K2S antigen.
Figure 2
Figure 2
(a) Number of antibodies against microbial antigens, excluding antibodies against SARS-CoV-2, in the sera of six groups stratified by antibody titer and the remaining neutralizing antibodies. The cross mark represents the mean while the box represents the median, 25th percentile, and 75th percentile. The upper and lower bars represent the minimum and maximum values. (b) The level of antibodies against spike proteins in various mutant strains of SARS-CoV-2. The fluorescence intensity ratios of the relative values against the negative controls are indicated as relative log2 ratios and are represented by the red intensity in the figure. (c) Shapley additive explanation (SHAP) values of antibodies against each microbial antigen, indicating their level of importance. The 10 antigens are shown in order of their SHAP values. * Victoria strain; § Tokio strain; † HPV-77 strain, BR2S antigen; ‡ HPV-77 strain, K2S antigen. (d) Relationship between the SHAP value and the feature value of antibodies against each microbial antigen. The feature value of a dot is positively correlated with high (red) and negatively correlated with low (blue) values. * Victoria strain; § Tokio strain; † HPV-77 strain, BR2S antigen; ‡ HPV-77 strain, K2S antigen.
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