Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients
Cristina Bergamaschi,
Evangelos Terpos,
Margherita Rosati,
Matthew Angel,
Jenifer Bear,
Dimitris Stellas,
Sevasti Karaliota,
Filia Apostolakou,
Tina Bagratuni,
Dimitris Patseas,
Sentiljana Gumeni,
Ioannis P. Trougakos,
Meletios A. Dimopoulos,
Barbara K. Felber,
George N. Pavlakis
Affiliations
Cristina Bergamaschi
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Evangelos Terpos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens 11528, Greece
Margherita Rosati
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Matthew Angel
Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cancer Research Collaborative Bioinformatics Resource, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
Jenifer Bear
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Dimitris Stellas
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Sevasti Karaliota
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
Filia Apostolakou
Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens 11527, Greece
Tina Bagratuni
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens 11528, Greece
Dimitris Patseas
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens 11528, Greece
Sentiljana Gumeni
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece
Ioannis P. Trougakos
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, Athens 15784, Greece
Meletios A. Dimopoulos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens 11528, Greece
Barbara K. Felber
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Corresponding author
George N. Pavlakis
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Corresponding author
Summary: 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.