1. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
- Author
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Fourati, Slim, Tomalin, Lewis E, Mulè, Matthew P, Chawla, Daniel G, Gerritsen, Bram, Rychkov, Dmitry, Henrich, Evan, Miller, Helen ER, Hagan, Thomas, Diray-Arce, Joann, Dunn, Patrick, Human Immunology Project Consortium (HIPC), Levy, Ofer, Gottardo, Raphael, Sarwal, Minnie M, Tsang, John S, Suárez-Fariñas, Mayte, Pulendran, Bali, Kleinstein, Steven H, Sékaly, Rafick-Pierre, Fourati, Slim [0000-0001-6609-7587], Tomalin, Lewis E [0000-0003-4545-7138], Chawla, Daniel G [0000-0001-7667-9337], Gerritsen, Bram [0000-0001-7065-3160], Hagan, Thomas [0000-0002-5254-5251], Dunn, Patrick [0000-0003-1868-9689], Levy, Ofer [0000-0002-5859-1945], Tsang, John S [0000-0003-3186-3047], Pulendran, Bali [0000-0001-6517-4333], Kleinstein, Steven H [0000-0003-4957-1544], Sékaly, Rafick-Pierre [0000-0002-7816-4828], and Apollo - University of Cambridge Repository
- Subjects
Vaccines ,Adjuvants, Immunologic ,Antibody Formation ,Vaccination ,Humans ,Immunity, Innate - Abstract
Several studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines. Analysis of blood transcriptional profiles across studies revealed three distinct pre-vaccination endotypes, characterized by the differential expression of genes associated with a pro-inflammatory response, cell proliferation, and metabolism alterations. Importantly, individuals whose pre-vaccination endotype was enriched in pro-inflammatory response genes known to be downstream of nuclear factor-kappa B showed significantly higher serum antibody responses 1 month after vaccination. This pro-inflammatory pre-vaccination endotype showed gene expression characteristic of the innate activation state triggered by Toll-like receptor ligands or adjuvants. These results demonstrate that wide variations in the transcriptional state of the immune system in humans can be a key determinant of responsiveness to vaccination.
- Published
- 2022