Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Slim Fourati, Lewis E. Tomalin, Matthew P. Mulè, Daniel G. Chawla, Bram Gerritsen, Dmitry Rychkov, Evan Henrich, Helen E. R. Miller, Thomas Hagan, Joann Diray‐Arce, Patrick Dunn, Alison Deckhut-Augustine, Elias K. Haddad, David A. Hafler, Eva Harris, Donna L. Färber, Julie McElrath, Ruth R. Montgomery, Bjoern Peters, Adeeb Rahman, Elaine F. Reed, Nadine Rouphael, Ana Fernández-Sesma, Alessandro Sette, Kenneth Stuart, Alkis Togias, Ofer Levy, Raphaël Gottardo, Minnie Sarwal, John S. Tsang, Mayte Suárez‐Fariñas, Bali Pulendran, Steven H. Kleinstein, Rafick‐Pierre Sékaly
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.