Trained Immunity Generated by the Recombinant Zoster Vaccine.

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Trained immunity, a form of innate immune memory, may contribute to vaccine efficacy.
• The efficacy of the recombinant zoster vaccine (RZV) and the live attenuated zoster vaccine (ZVL) against herpes zoster varies.
• Understanding the mechanisms of vaccine-induced protection is crucial for developing better vaccines.

Purpose of the Study:

• To investigate whether the RZV induces trained immunity.
• To compare the induction of trained immunity by RZV versus ZVL.
• To explore the cellular and molecular mechanisms underlying RZV-induced trained immunity.

Main Methods:

• Ex vivo stimulation of immune cells from vaccinated individuals.
• Flow cytometry to assess immune cell responses.
• ATAC-seq to analyze chromatin accessibility.
• TGFβ1 manipulation experiments.

Main Results:

• RZV, but not ZVL, induced trained immunity in monocytes, NK cells, and DCs.
• RZV-induced responses were gE-specific and persisted for at least 4 years.
• RZV enhanced heterologous responses to other herpesviruses.
• Decreased TGFβ1 transcription due to RZV-induced chromatin modifications was linked to monocyte trained immunity.

Conclusions:

• RZV confers trained immunity, potentially contributing to its high efficacy.
• Epigenetic modifications and altered TGFβ1 signaling are implicated in RZV-induced trained immunity.
• Further research is needed to elucidate the role of RZV-trained immunity in protection against herpes zoster and other infections.