Impact of an intranasal L-DBF vaccine on the gut microbiota in young and elderly mice

Abstract

ABSTRACT Shigella spp. cause bacillary dysentery (shigellosis) with high morbidity and mortality in low- and middle-income countries. Infection occurs through the fecal-oral route and can be devastating for vulnerable populations, including infants and the elderly. These bacteria invade host cells using a type III secretion system (T3SS). No licensed vaccine yet exists for shigellosis, but we have generated a recombinant fusion protein, L-DBF, combining the T3SS needle tip protein (IpaD), translocator protein (IpaB), and the LTA1 subunit of enterotoxigenic E. coli labile toxin, which offers broad protection in a mouse model of lethal pulmonary infection. The L-DBF vaccine protects high-risk groups, including young and elderly mice. Here, we investigated how the gut microbiota of young and elderly mice responds to intranasal L-DBF vaccination formulated in an oil-in-water emulsion (ME). Samples from lungs, small intestines, and feces were collected on day 14 after 2 or 3 doses of L-DBF in ME. 16S rRNA gene sequencing revealed age-dependent changes in gut microbiota post-vaccination. The vaccine-induced changes were more prominent in the elderly mice and were most significant in the intestinal tract, indicating that vaccination by the intranasal route can have a tremendous impact on the gut environment. These findings provide insight into the communication between the intranasal mucosal surface following subunit vaccination and the microbiota at a distant mucosal site, thereby highlighting the impact of vaccination and the host’s microbiome.