Composition of the murine gut microbiome impacts humoral immunity induced by rabies vaccines.

ABSTRACT

BACKGROUND: Gut microbiome plays a crucial role in modulating human and animal immune responses. Rabies is a fatal zoonosis causing encephalitis in mammals and vaccination is the most effective method to control and eliminate rabies. The relationship between the gut microbiome and humoral immunity post rabies vaccination has not been investigated yet. METHODS: Mice orally administrated with a cocktail of broad-spectrum antibiotics were inoculated with rabies vaccines, and humoral immune response was analyzed at indicated time points. The 16S ribosomal RNA (16S rRNA) gene sequencing was performed on fecal samples from groups in vancomycin-treated and untreated mice. Mice were immunized with rabies vaccines and virus-neutralizing antibody (VNA) levels were measured, resulting in VNA high (H) and low (L) groups. Then 16S rRNA gene sequencing was performed on fecal samples from H and L group mice. RESULTS: After antibiotic (Abx) treatment, mice had decreased levels of rabies virus (RABV)-specific IgM, IgG, and virus-neutralizing antibody compared with untreated mice. Abx-treated mice had fewer T follicular helper cells, germinal center B cells, and antibody secreting cells (ASCs) in lymph nodes than did untreated mice. Gut microbiome facilitated secondary immune responses by increasing the generation of ASCs. Treatment with vancomycin alone had a similarly impaired effect on the humoral immune responses compared with Abx-treated mice. From the natural population group of mice received rabies vaccines, VNA titers vary significantly and the abundance of Clostridiales and Lachnospiraceae was positively associated with the antibody titers in mice. CONCLUSIONS: Our results provide the evidence that the gut microbiome impacts humoral immunity post rabies vaccination, and further investigation of the mechanism will help the development of novel adjuvants and vaccines.