A specific anti-COVID-19 BNT162b2 vaccine-induced early innate immune signature positively correlates with the humoral protective response in healthy and multiple sclerosis vaccine recipients.

The very rapidly approved mRNA-based vaccines against SARS-CoV-2 spike glycoprotein, including Pfizer-BioNTech BNT162b2, are effective in protecting from severe coronavirus disease 2019 (COVID-19) in immunocompetent population. However, establishing the duration and identifying correlates of vaccine-induced protection will be crucial to optimise future immunisation strategies. Here, we studied in healthy vaccine recipients and people with multiple sclerosis (pwMS), undergoing different therapies, the regulation of innate immune response by mRNA vaccination in order to correlate it with the magnitude of vaccine-induced protective humoral responses. Healthy subjects ( We identified an early immune module composed of the IFN-inducible genes Mx1, OAS1 and IRF1, the serum cytokines IL-15, IL-6, TNF-α and IFN-γ and the chemokines IP-10, MCP-1 and MIG, induced 1 day post second and third BNT162b2 vaccine doses, strongly correlating with magnitude of humoral response to vaccination in healthy and MS vaccinees. Moreover, induction of the early immune module was dramatically affected in pwMS treated with fingolimod and ocrelizumab, both groups unable to induce a protective humoral response to COVID-19 vaccine. Overall, this study suggests that the vaccine-induced early regulation of innate immunity is mediated by IFN signalling, impacts on the magnitude of adaptive responses and it might be indicative of vaccine-induced humoral protection.

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© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Déclaration de conflit d'intérêts

Severa M, Rizzo F, Ricci D, Etna MP, Sinigaglia A, Buscarinu MC, Valdarchi C, Piubelli C, Gobbi F, Ristori G, Riccetti S, Cola G, Palmerini P, Rosato A, Balducci S, Barzon L and Coccia EM declare no conflict of interest. Salvetti M received research support and consulting fees from Biogen, Merck, Novartis, Roche, Sanofi, Teva. Landi D received travel funding from Biogen, Merck Serono, Sanofi‐Genzyme and Teva, honoraria for speaking from Sanofi‐Genzyme and Teva, and consultation fees from Merck Serono and Teva. She is sub‐investigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva. Girolama MA is an Advisory Board member of Biogen Idec, Genzyme, Merck‐Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi‐Genzyme, Roche, Mylan, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi‐Genzyme, Merck Serono and Teva.