Systemic IL-15, IFN-γ and IP-10/CXCL10 Signature Associated with Effective Immune Response to SARS-CoV-2 in BNT162b2 mRNA Vaccine Recipients

Bergamaschi, Cristina; Terpos, Evangelos; Rosati, Margherita; Angel, Matthew; Bear, Jenifer; Stellas, Dimitris; Karaliota, Sevasti; Apostolakou, Filia; Bagratuni, Tina; Patseas, Dimitris; Gumeni, Sentiljana; Trougakos, Ioannis P.; Dimopoulos, Meletios A.; Felber, Barbara K.; Pavlakis, George N.

Early responses to vaccination are important in shaping both humoral and cellular protective immunity. Dissecting innate vaccine signatures may predict immunogenicity to help optimizing efficacy of mRNA and other vaccine strategies. We characterized the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naïve and in previously COVID-19-infected individuals (NCT04743388). Transient increases in IL-15 and IFN-γ levels early after boost correlated with Spike antibody levels, supporting their use as biomarkers of effective humoral immunity development in response to vaccination. We identified a systemic signature including IL-15, IFN-γ and IP-10/CXCL10 increase after the 1st vaccination, which was enriched by TNF-α and IL-6 after the 2nd vaccination. In previously COVID-19-infected individuals, a single vaccination resulted in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naïve individuals, a result with potential implication for future public health recommendations.