Immuno-microbial signature of vaccine-induced immunity of SARS-CoV-2

Although vaccines address critical public health needs, inter-individual differences in re- 14 sponses are not always considered in their development. Determining vaccine effectiveness on an 15 individual basis is a concern in outbreak response and disease control. In this pilot study, pre- and 16 post- antiviral, immunological, and gut microbiota responses were characterized to examine the 17 effectiveness of the SARS-CoV-2 mRNA inoculation. Blood and stool samples were collected before 18 administration of the biological products and at 2-to-4-week intervals after the administration of the 19 first dose. A cohort of 14 adults were separated into two groups based on the neutralizing antibody 20 levels after 10 weeks of inoculation: high neutralization (HN) and low neutralization (LN). Bivariate 21correlation analysis was performed to examine associations between gut microbiota, inflammation 22 response and neutralization capacity at 10-weeks post-vaccination. This analysis between the two 23 groups indicates significant differences in gut microbiota composition and inflammatory factors 24 with significant correlations between bacterial species found at higher abundance in the HN group 25 being negatively correlated to a panel of inflammation factors. There was also a significant inverse 26 relationship (R=-0.5, p=0.03) between HMGB-1 plasma concentrations pre-vaccination and neutral- 27 ization capacity at 10 weeks post inoculation period. Altogether, our results implicate that HMGB- 28 1 is a potential biomarker in predicting SARS-CoV-2 mRNA vaccine effectiveness.