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Article

Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines

by
Lauren Daddi
1,†,
Yair Dorsett
1,†,
Tingting Geng
2,
Suresh Bokoliya
1,
Hanshu Yuan
1,
Penghua Wang
2,
Wanli Xu
3,* and
Yanjiao Zhou
1,*
1
Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
2
Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA
3
School of Nursing, University of Connecticut, Storrs, CT 06269, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work and are co-first authors.
Int. J. Mol. Sci. 2023, 24(14), 11703; https://doi.org/10.3390/ijms241411703
Submission received: 30 May 2023 / Revised: 1 July 2023 / Accepted: 12 July 2023 / Published: 20 July 2023
(This article belongs to the Special Issue A Commemorative Issue Honoring Biomolecular Scientists in the Post-COVID-19 Pandemic Era)
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Abstract

The powerful immune responses elicited by the mRNA vaccines targeting the SARS-CoV-2 Spike protein contribute to their high efficacy. Yet, their efficacy can vary greatly between individuals. For vaccines not based on mRNA, cumulative evidence suggests that differences in the composition of the gut microbiome, which impact vaccine immunogenicity, are some of the factors that contribute to variations in efficacy. However, it is unclear if the microbiome impacts the novel mode of immunogenicity of the SARS-CoV-2 mRNA vaccines. We conducted a prospective longitudinal cohort study of individuals receiving SARS-CoV-2 mRNA vaccines where we measured levels of anti-Spike IgG and characterized microbiome composition, at pre-vaccination (baseline), and one week following the first and second immunizations. While we found that microbial diversity at all timepoints correlated with final IgG levels, only at baseline did microbial composition and predicted function correlate with vaccine immunogenicity. Specifically, the phylum Desulfobacterota and genus Bilophila, producers of immunostimulatory LPS, positively correlated with IgG, while Bacteroides was negatively correlated. KEGG predicted pathways relating to SCFA metabolism and sulfur metabolism, as well as structural components such as flagellin and capsular polysaccharides, also positively correlated with IgG levels. Consistent with these findings, depleting the microbiome with antibiotics reduced the immunogenicity of the BNT162b2 vaccine in mice. These findings suggest that gut microbiome composition impacts the immunogenicity of the SARS-CoV-2 mRNA vaccines.
Keywords: COVID-19; mRNA vaccines; microbiome; gut microbiome; SARS-CoV-2 mRNA vaccines; vaccine efficacy; microbial diversity; Bilophila; Desulfobacterota; immunization COVID-19; mRNA vaccines; microbiome; gut microbiome; SARS-CoV-2 mRNA vaccines; vaccine efficacy; microbial diversity; Bilophila; Desulfobacterota; immunization

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MDPI and ACS Style

Daddi, L.; Dorsett, Y.; Geng, T.; Bokoliya, S.; Yuan, H.; Wang, P.; Xu, W.; Zhou, Y. Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines. Int. J. Mol. Sci. 2023, 24, 11703. https://doi.org/10.3390/ijms241411703

AMA Style

Daddi L, Dorsett Y, Geng T, Bokoliya S, Yuan H, Wang P, Xu W, Zhou Y. Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines. International Journal of Molecular Sciences. 2023; 24(14):11703. https://doi.org/10.3390/ijms241411703

Chicago/Turabian Style

Daddi, Lauren, Yair Dorsett, Tingting Geng, Suresh Bokoliya, Hanshu Yuan, Penghua Wang, Wanli Xu, and Yanjiao Zhou. 2023. "Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines" International Journal of Molecular Sciences 24, no. 14: 11703. https://doi.org/10.3390/ijms241411703

APA Style

Daddi, L., Dorsett, Y., Geng, T., Bokoliya, S., Yuan, H., Wang, P., Xu, W., & Zhou, Y. (2023). Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines. International Journal of Molecular Sciences, 24(14), 11703. https://doi.org/10.3390/ijms241411703

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