# Innate Immunity Trained in the Protective Response of Vaccine Candidates Against Intracellular Pathogens

## TL;DR

This study shows that trained innate immunity can boost the effectiveness of inactivated vaccines against certain bacterial infections but may reduce the effectiveness of live vaccines.

## Contribution

The study reveals that β-glucan enhances inactivated vaccine efficacy against Brucella ovis and Listeria monocytogenes but impairs live attenuated vaccine performance.

## Key findings

- β-glucan reduced bacterial colonization in mice vaccinated with gamma-irradiated Brucella ovis.
- 50% of trained and vaccinated mice showed no detectable Listeria monocytogenes after challenge.
- Overstimulation with β-glucan doses impaired infection control, suggesting a negative effect on trained immunity.

## Abstract

Background/Objectives: Trained innate immunity refers to the enhanced responsiveness of innate immune cells, particularly macrophages, following exposure to stimuli such as β-glucan or zymosan, enabling improved defense against unrelated pathogens. This phenomenon has been widely investigated to better understand host–pathogen interactions and to support the development of improved infection control strategies. This study evaluated whether these training stimuli could enhance the protective efficacy of attenuated or inactivated vaccine models against Brucella ovis and Listeria monocytogenes infection. Methods: Trained innate immunity was induced in vivo using β-glucan or zymosan, and seven days later mice were vaccinated with attenuated or gamma-irradiated formulations and subsequently challenged with B. ovis or L. monocytogenes. Vaccine-induced protection and immune responses were assessed through multiple experimental approaches. Results: β-glucan significantly reduced bacterial infection in vitro in bone-marrow-derived macrophages and in vivo in target organs compared with zymosan. Although β-glucan did not enhance the efficacy of the attenuated B. ovis ΔabcBA vaccine, it markedly reduced bacterial colonization in mice vaccinated with gamma-irradiated B. ovis. β-glucan also did not improve the efficacy of the gamma-irradiated L. monocytogenes vaccine; however, 50% of the trained and vaccinated mice showed no detectable bacterial recovery. Increasing the number of β-glucan doses negatively affected infection control, suggesting that overstimulation may impair trained immunity. Conclusion: Trained innate immunity enhances the protective effect of inactivated experimental vaccines against B. ovis and L. monocytogenes, while exerting a detrimental influence on the efficacy of a live attenuated B. ovis vaccine model.