Trained Immunity Induced by Vaccines: A Shifting Paradigm for Infant and Adult Immunity.

Area of Science:

• Immunology
• Vaccinology
• Innate Immunity

Background:

• Vaccines induce adaptive immunity but can also train the innate immune system, enhancing host protection.
• Trained immunity (TRIM) is a concept supported by laboratory evidence, but its clinical translation requires further investigation.
• Understanding TRIM's mechanisms, such as epigenetic and metabolic changes, is crucial for optimizing vaccine efficacy.

Purpose of the Study:

• To review and evaluate the evidence for vaccine-induced trained immunity (TRIM).
• To translate current findings on TRIM into a clinical context.
• To identify gaps in knowledge regarding TRIM mechanisms and vaccine-specific responses.

Main Methods:

• Literature review of studies investigating vaccine-induced trained immunity.
• Analysis of laboratory methods used to assess TRIM.
• Examination of mechanistic studies focusing on epigenetic reprogramming and metabolic rewiring.

Main Results:

• Live-attenuated vaccines generally induce TRIM, characterized by increased inflammatory cytokine production upon restimulation.
• Non-live vaccines tend to show reduced trained immunity, while mRNA vaccines exhibit heterogeneous TRIM patterns.
• Inconsistent results are reported for non-BCG vaccines, highlighting the need for more reliable studies.

Conclusions:

• A deeper understanding of TRIM mechanisms and vaccine-specific responses is essential for rational vaccine design.
• Factors like vaccine type, administration route, sex, and age can modify vaccine-induced TRIM.
• Considering these modifiers is critical for optimizing vaccine administration strategies to enhance immune protection.