Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses

• Published in: Nature immunology Vol. 23; no. 12; pp. 1788 - 1798
• Main Authors: Hagan, Thomas, Gerritsen, Bram, Tomalin, Lewis E., Fourati, Slim, Mulè, Matthew P., Chawla, Daniel G., Rychkov, Dmitri, Henrich, Evan, Miller, Helen E. R., Diray-Arce, Joann, Dunn, Patrick, Lee, Audrey, Levy, Ofer, Gottardo, Raphael, Sarwal, Minne M., Tsang, John S., Suárez-Fariñas, Mayte, Sékaly, Rafick-Pierre, Kleinstein, Steven H., Pulendran, Bali
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2022; Nature Publishing Group
• Subjects: 631/250; 631/250/590; Adult; Antibodies; Antibodies, Viral; Antibody Formation - genetics; Antibody response; Biomedical and Life Sciences; Biomedicine; Cell activation; Comparative analysis; Gene Expression Profiling - methods; Heterogeneity; Humans; Immune response; Immunity, Innate; Immunology; Infectious Diseases; Innate immunity; Interferon; Resource; Transcription; Vaccination; Vaccines; Vector-borne diseases; Yellow fever; Young adults
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-022-01328-6

Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14–21, respectively. Thus, there was no evidence for a ‘universal signature’ that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses. Pulendran and colleagues perform a comparative analysis of transcriptional responses of healthy young adults across 13 different vaccines. They find that while a common transcriptional program is shared across many vaccines, there is significant heterogeneity especially in the kinetics of immune responses.