Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 9 May 2024 / Approved: 13 May 2024 / Online: 13 May 2024 (06:48:28 CEST)

How to cite: Vilander, A. C.; Burak, J.; Gilfillan, D.; Dean, G. A.; Abdo, Z. Host Functional Response to a Prototypic Orally Delivered Self-Replicating Vaccine Platform. Preprints 2024, 2024050784. https://doi.org/10.20944/preprints202405.0784.v1 Vilander, A. C.; Burak, J.; Gilfillan, D.; Dean, G. A.; Abdo, Z. Host Functional Response to a Prototypic Orally Delivered Self-Replicating Vaccine Platform. Preprints 2024, 2024050784. https://doi.org/10.20944/preprints202405.0784.v1

Abstract

Development of mucosal vaccines has been limited and could be aided by a systems vaccinology approach to identify platforms and adjuvant strategies that induce protective immune responses. Induction of local immune responses by mucosal-delivered vaccines has been difficult to evaluate from peripheral samples as systemic responses often do not correlate with the mucosal response. Here we utilized transcriptomics in combination with Gene Set Enrichment Analysis (GSEA) to assess innate immune activation by an oral probiotic Lactobacillus acidophilus-based vaccine platform in mice. The goal was to explore the earliest immune responses elicited after oral immunization at the Peyer’s patch. Twenty-four hours after oral delivery of the L. acidophilus vaccine platform, we found an overabundance of L. acidophilus at Peyer’s patches and detected expression of the vaccine viral proteins and adjuvants confirming in vivo vaccine delivery. Compared to mice orally dosed with buffer or wild-type L. acidophilus, we identified enhanced response in immune pathways related to cytokine and gene signaling, T and B cell activation, phagocytosis, and humoral responses. While more work is needed to correlate these pathways with protection from infection and/or disease, they indicate this method’s potential to evaluate and aid in the iterative development of next-generation mucosal vaccines.

Keywords

systems vaccinology; Lactobacillus acidophilus; mucosal vaccines; transcriptomics

Subject

Medicine and Pharmacology, Immunology and Allergy

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