Early biomarkers for an effective antibody responses after SARS-CoV-2 BNT162b2 mRNA vaccination in humans

Authors

• S Devasundaram
• M Rosati
• C Bergamaschi
• J Bear
• R Burns
• P Homan
• MA Dimpoulus
• E Termos
• GN Panlakis
• BK Felber

Abstract

Background
Early innate responses to vaccination are important for shaping both humoral and cellular protective immunity. Dissecting biomarkers induced by BNT162b2 mRNA (Pfizer/BioNtech) vaccine (NCT04743388) may lead to optimization of mRNA and other vaccine strategies.

Methods
Plasma was analyzed after the 1st, 2nd and 3rd vaccination (NCT04743388). Cytokine/chemokine changes were measured using V-PLEX Human Biomarker Assay (Meso Scale Diagnostics) and ELISA (CXCL13, Invitrogen) at the day of vaccination and 24hrs later. Anti-spike binding and neutralizing Ab were measured over time using in-house ELISA and a pseudotyped virus assay.

Results
Vaccination induced robust anti-Spike Ab with a significant enhancement upon the 3rd vaccination. We identified a transient systemic signature including increases in IL-15, IFN-gamma, and IP-10/CXCL10 after the 1st vaccination, enriched by TNF-alpha and IL-6 after the 2nd and 3rd vaccination. Changes in biomarker levels and their inter-relationship revealed two major clusters: including (i) IL-15, IFN-gamma, CXCL10/IP-10 and (ii) myeloid cell-associated cytokines CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CXCL8/IL-8. Additionally, CXCL13 induction upon the 3rd vaccination indicated a stronger effect on lymph node activation only upon repeated vaccination. Changes in IFN-gamma and IP-10/CXCL10 correlated with the anti-Spike humoral responses and were predictive of successful antibody development. In contrast, most hematological patients showed diminished IL-15 signature and antibody responses. Patients who failed to develop antibodies, also lacked the IL-15 signature and had an innate systemic response dominated by IL-8 and MIP-1a.

Conclusion
These data identified a transient cytokine signature featuring IFN-gamma, IL-15 and IP-10/CXCL10 associated with protective adaptive responses to the BNT162b2 mRNA vaccine.

Scientific Focus Area: Immunology

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