The Safety of Alcaligenes Lipid A in a Virus-Induced Immune Disease Model Associated with IgA, Th17 Cells, and Microbiota

Lipid A is a component of lipopolysaccharide (LPS) of Gram-negative bacteria. Previously, we demonstrated that synthesized lipid A derived from Alcaligenes faecalis (ALA) could enhance antigen-specific immunoglobulin (Ig) A and T helper (Th) 17 responses, when ALA was co-administered experimentally with an antigen as a vaccine adjuvant. This raised concerns about the safety of the ALA usage, since IgA and Th17 responses have been suggested to play a pathogenic role in several immune-mediated diseases, including multiple sclerosis (MS). We investigated whether ALA administrations could exacerbate an animal model of MS, Theiler’s murine encephalomyelitis virus (TMEV) infection. TMEV-infected SJL/J mice were administered ALA at various time points, and their neurological signs were observed for 7 weeks. We found that ALA administrations did not exacerbate TMEV-induced inflammatory disease or viral persistence in the central nervous system (CNS), clinically or histologically. Furthermore, ALA administrations did not enhance TMEV-specific humoral and cellular responses, including IgA and Th17 responses. On the other hand, principal component analysis (PCA) of the fecal, not the ileal, samples showed significant changes in the microbiota, characterized by increases in the relative abundance of bacteria belonging to the phylum Bacteroidota, including the genera Alistipes and Bacteroides. Therefore, ALA injections could be safe for use in immune-mediated diseases, whose immunopathology has been associated with IgA and Th17 responses.