Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients

• Published in: Cell reports (Cambridge) Vol. 36; no. 6; p. 109504
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2021; The Author(s); Elsevier
• Subjects: Adult; Aged; Antibodies, Viral - immunology; BNT162 Vaccine; Chemokine CXCL10 - immunology; COVID-19 - immunology; COVID-19 - metabolism; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; cytokines; Female; Humans; IFN-γ; IL-15; Immunity - immunology; innate immunity; Interferon-gamma - immunology; Interleukin-15 - immunology; IP10/CXCL10; Male; Middle Aged; mRNA vaccine; RNA, Messenger - immunology; SARS-CoV-2; SARS-CoV-2 - immunology; Spike antibody; SARS-CoV-2; IFN-γ; Spike antibody; innate immunity; IL-15; cytokines; IP10/CXCL10; mRNA vaccine
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109504

Early responses to vaccination are important for shaping both humoral and cellular protective immunity. Dissecting innate vaccine signatures may predict immunogenicity to help optimize the efficacy of mRNA and other vaccine strategies. Here, we characterize the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naive and in previously coronavirus disease 2019 (COVID-19)-infected individuals (NCT04743388). Transient increases in interleukin-15 (IL-15) and interferon gamma (IFN-γ) levels early after boost correlate with Spike antibody levels, supporting their use as biomarkers of effective humoral immunity development in response to vaccination. We identify a systemic signature including increases in IL-15, IFN-γ, and IP-10/CXCL10 after the 1st vaccination, which were enriched by tumor necrosis factor alpha (TNF-α) and IL-6 after the 2nd vaccination. In previously COVID-19-infected individuals, a single vaccination results in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naive individuals, a result with potential implication for future public health recommendations. [Display omitted] •BNT162b2 mRNA vaccine induces a cytokine signature featuring IL-15, IFN-γ, and CXCL10•mRNA-vaccine-induced IFN-γ and IL-15 correlate with spike antibody response•Strong cytokine signature upon a single vaccination of convalescent persons•Stronger cytokine induction upon booster vaccination in naive persons Bergamaschi et al. find that the SARS-CoV-2 BNT162b2 mRNA vaccine induces a distinct transient cytokine response featuring IL-15, IFN-γ, and IP-10/CXCL10. mRNA-vaccine-induced IFN-γ and IL-15 correlate with spike antibody response. A single vaccination of convalescent persons leads to both robust cytokine signature and antibody response.