Host Functional Response to a Prototypic Orally Delivered Self-Replicating Vaccine Platform.

Area of Science:

• Immunology
• Vaccinology
• Microbiome research

Background:

• Mucosal vaccine development is challenging due to difficulties in evaluating local immune responses.
• Systems vaccinology offers a promising approach to identify effective mucosal vaccine platforms and adjuvants.
• Assessing early innate immune activation is crucial for understanding vaccine efficacy.

Purpose of the Study:

• To evaluate innate immune activation by an oral probiotic (Lactobacillus acidophilus)-based vaccine platform in mice using transcriptomics.
• To identify early immune responses at the Peyer's patch following oral immunization.
• To explore the potential of systems vaccinology for developing next-generation mucosal vaccines.

Main Methods:

• Oral immunization of mice with a Lactobacillus acidophilus-based vaccine platform.
• Transcriptomic analysis of Peyer's patches 24 hours post-immunization.
• Gene Set Enrichment Analysis (GSEA) to identify activated immune pathways.

Main Results:

• Confirmation of in vivo vaccine delivery, with Lactobacillus acidophilus and vaccine antigens detected in Peyer's patches.
• Identification of enhanced immune responses in pathways including cytokine signaling, T and B cell activation, phagocytosis, and humoral immunity compared to controls.
• Significant upregulation of innate immune pathways following oral vaccination.

Conclusions:

• The study demonstrates the utility of transcriptomics and GSEA for assessing early immune responses to mucosal vaccines.
• The identified immune pathways provide insights into the mechanism of action of the Lactobacillus acidophilus-based vaccine.
• This approach can aid in the iterative development and optimization of novel mucosal vaccine strategies.