Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine

Area of Science:

• * Immunology
• * Molecular Biology
• * Vaccinology

Background:

• * Ebolavirus Disease (EVD) is a severe hemorrhagic fever with high fatality and no specific treatments.
• * The rVSVΔG-ZEBOV-GP (Ervebo) vaccine is the first approved for EVD prevention.
• * Vaccine-induced protection mechanisms involving innate and adaptive immunity require further elucidation.

Purpose of the Study:

• * To investigate the host blood response signature following vaccination with rVSVΔG-ZEBOV-GP.
• * To identify blood transcription modules (BTMs) affected by the vaccine.
• * To correlate transcriptomic changes with antibody responses.

Main Methods:

• * A global transcriptomic approach was employed to profile blood host responses.
• * 51 healthy volunteers participated in a phase 1/2 clinical trial.
• * Differentially expressed genes (DEGs) and BTMs were analyzed post-vaccination.

Main Results:

• * Vaccination induced a peak of 5469 DEGs at day one, affecting 144 out of 346 BTMs.
• * Innate immunity pathways were induced from day 1 to 14; neutrophil modules downregulated, complement modules upregulated.
• * T-cell and cell-cycle modules upregulated at days 7-14; correlation observed between antibody titres and seven BTMs, including B-cell related modules.

Conclusions:

• * Transcriptomic analysis identified a distinct rVSVΔG-ZEBOV-GP-induced host response signature.
• * The study demonstrated a direct correlation between blood transcriptomic changes and EVD vaccine-specific antibody titres.
• * These findings enhance understanding of the immunological mechanisms underlying EVD vaccine efficacy.