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.

Vaccine Hyporesponse Induced by Individual Antibiotic Treatment in Mice and Non-Human Primates Is Diminished upon Recovery of the Gut Microbiome

“…Vancomycin also demonstrated consistent vaccine-modulatory effects of subsequent studies wherein: (i) vancomycin, but not ampicillin, robustly impacted alum-adjuvant OVA vaccine-specific titers in a different mouse strain (C57Bl/6; Figure S3A); (ii) vancomycin decreased antigenspecific IgG titers and T cell responses when mice were vaccinated with OVA adjuvanted with a novel lipid nanoparticle (LNP)-based adjuvant (Figure S4A-D); and (iii) vancomycin reduced antigen-specific IgG titers against a clinically relevant hepatitis B vaccine conducted in two geographically distinct vivaria (Figure S4E-F). Vancomycin treatment has previously been shown to disrupt response to nonadjuvanted inactivated influenza vaccine [22] and rabies vaccine [54], and is included in many antibiotic cocktails used to perturb the microbiome for vaccination studies with variable effects on individual vaccine antigens [22,26,28,54]. Vancomycin treatment has also been shown to modulate several immune-related pathways [55][56][57][58], and reduces the abundance of bacteria belonging to Clostridiales and Bacteroidales, while allowing increases in Proteobacteria [55][56][57][58][59], in agreement with our data (Figure 1C).…”

Immunomodulation by the Commensal Microbiome During Immune-Targeted Interventions: Focus on Cancer Immune Checkpoint Inhibitor Therapy and Vaccination

“…Since the 1960s, germ-free mouse, chicken, and pig models have demonstrated that the microbiome influences vaccine response ( 119 – 124 ). More recently, microbiota disruption via antibiotic treatment in mice has corroborated these early observations ( 125 – 127 , 130 , 131 , 133 ). Multiple antibiotics from different classes and with different breadths of activity have been shown to decrease vaccine response ( Table 3 ).…”

Different Responses of Microbiota across Intestinal Tract to Enterococcus faecium HDRsEf1 and Their Correlation with Inflammation in Weaned Piglets

“…The PCR reactions were conducted using the following program: denaturation at 95 °C for 3 min, 27 cycles of 95 °C for 30 s, annealing at 55 °C for 30 s, elongation at 72 °C for 45 s, and a final extension at 72 °C for 10 min. The PCR components, the extraction and purification of PCR products were the same with previous study [ 29 ]. Purified PCR products were pooled into equimolar amounts and sequenced on the Illumina MiSeq platform according to the standard protocols by Shanghai Majorbio Bio-pharm Technology Co., Ltd. (Shanghai, China).…”