Journal Article

Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination

Sékaly, Rafick-Pierre, Rouphael, Nadine, Chawla, Daniel G, Sette, Alessandro, Diray-Arce, Joann, McElrath, Julie, Haddad, Elias K, Miller, Helen E. R, Levy, Ofer, Harris, Eva, Dunn, Patrick, Togias, Alkis, Gottardo, Raphael, Farber, Donna, Fourati, Slim, Reed, Elaine F, Hagan, Thomas, Deckhut-Augustine, Alison, Rahman, Adeeb, Peters, Bjoern, Kleinstein, Steven H, Montgomery, Ruth R, Pulendran, Bali, Tomalin, Lewis E, Mulè, Matthew P, Fernandez-Sesma, Ana, Hafler, David A, Henrich, Evan, Tsang, John S, Suárez-Fariñas, Mayte, Rychkov, Dmitry, Sarwal, Minnie M, Stuart, Kenneth D, Gerritsen, Bram

2022

Overview

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.Sekaly and colleagues reveal a common pre-vaccination peripheral blood transcriptional signature that is predictive of antibody responses across 13 different vaccines.

• Publisher: Nature Publishing Group
• Subject: Adjuvants / Antibodies / Antibody response / Cell proliferation / Gene expression / Immune response / Immune system / Inflammation / NF-κB protein / Peripheral blood / Toll-like receptors / Transcription / Vaccines