Skip to main content
Evidence-Based Supplement Research
Evidence-Based Supplement Research
Pillser
Search
Sign UpLog In

Nasal delivery of killed Bacillus subtilis spores protects against influenza, RSV and SARS-CoV-2.

  • 2025-04-02
  • Frontiers in immunology 16
    • Rong Xu
    • Huynh A Hong
    • Shadia Khandaker
    • Murielle Baltazar
    • Noor Allehyani
    • Daan Beentjes
    • Tessa Prince
    • Yen-Linh Ho
    • Linh Hanh Nguyen
    • Daniel Hynes
    • William Love
    • Simon M Cutting
    • Aras Kadioglu

Study Design

Population
mice
Methods
In vivo viral challenge murine models were used to assess the prophylactic anti-viral effects of B. subtilis spores delivered by intranasal instilling, using an optimised three-dose regimen. Multiple nasal boosting doses following intramuscular priming with SARS-CoV-2 spike protein was also tested.

Introduction

Spores of the bacterium Bacillus subtilis (B. subtilis) have been shown to carry a number of properties potentially beneficial for vaccination. Firstly, as vehicles enabling mucosal delivery of heterologous antigens and secondly, as stimulators of innate immunity. Here, we have examined the specificity of protection conferred by the spore-induced innate response, focusing on influenza H1N1, respiratory syncytial virus (RSV), and coronavirus-2 (SARS-CoV-2) infections.

Methods

In vivo viral challenge murine models were used to assess the prophylactic anti-viral effects of B. subtilis spores delivered by intranasal instilling, using an optimised three-dose regimen. Multiple nasal boosting doses following intramuscular priming with SARS-CoV-2 spike protein was also tested for the capability of spores on enhancing the efficacy of parenteral vaccination. To determine the impact of spores on immune cell trafficking to lungs, we used intravascular staining to characterise cellular participants in spore-dosed pulmonary compartments (airway and lung parenchyma) before and after viral challenge.

Results

We found that mice pre-treated with spores developed resistance to all three pathogens and, in each case, exhibited a significant improvement in both survival rate and disease severity. Intranasal spore dosing expanded alveolar macrophages and induced recruitment of leukocyte populations, providing a cellular mechanism for the protection. Most importantly, virus-induced inflammatory leukocyte infiltration was attenuated in spore-treated lungs, which may alleviate the associated collateral tissue damage that leads to the development of severe conditions. Remarkably, spores were able to promote the induction of tissue-resident memory T cells, and, when administered following an intramuscular prime with SARS-CoV-2 spike protein, increased the levels of anti-spike IgA and IgG in the lung and serum.

Conclusions

Taken together, our results show that Bacillus spores are able to regulate both innate and adaptive immunity, providing heterologous protection against a variety of important respiratory viruses of high global disease burden.

Research Insights

  • Bacillus clausii SC-109→Reduced Infection Severity

    mice pre-treated with spores developed resistance to all three pathogens and, in each case, exhibited a significant improvement in both survival rate and disease severity.

    Effect
    Beneficial
    Effect size
    Large
Back to top