Acute and persistent responses after H5N1 vaccination in humans

Area of Science:

• Systems immunology
• Vaccinology
• Computational biology

Background:

• Adjuvants are critical for enhancing vaccine immunogenicity.
• Understanding early immune responses to vaccination is key to vaccine design.

Purpose of the Study:

• To investigate the impact of the AS03 adjuvant on human H5N1 influenza vaccination responses.
• To identify early immune response dynamics associated with adjuvant use and immunogenicity.

Main Methods:

• Longitudinal systems immunology approach with 14 time points.
• Unsupervised computational framework for discovering high-dimensional response patterns.
• Single-cell profiling (surface proteins, transcriptomes, chromatin accessibility).

Main Results:

• Discovered adjuvant- and immunogenicity-associated early response dynamics, differing post-prime vs. post-boost.
• Identified persistent vaccine-induced transcriptional patterns up to 100 days.
• Erythroblast-transformation-specific (ETS) transcription factors shape long-lasting signatures in monocytes and CD8+ T cells.

Conclusions:

• Adjuvant AS03 modulates early and long-lasting immune signatures following H5N1 influenza vaccination.
• Baseline immune states, potentially influenced by vaccine antigens, predict high antibody responses.
• Findings suggest antigen-agnostic immune states can be modulated to enhance vaccine efficacy.