Vaccination with an HIV T-cell immunogen induces alterations in the mouse gut microbiota

Abstract

The gut microbiota is emerging as a crucial factor modulating vaccine responses; however, few studies have investigated if vaccines, in turn, can alter the microbiota and to what extent such changes may improve vaccine efficacy. To understand the effect of T-cell vaccination on the gut microbiome, we administered an HIV-1 T-cell immunogen (HTI arm) or PBS (control, Mock arm) to C57Bl/6 mice following a heterologous prime-boost scheme. The longitudinal dynamics of the mice gut microbiota was characterized by 16 S ribosomal RNA sequencing in fecal samples collected from cages, as well as from three gut sections (cecum, small and large intestine). Serum and spleen cells were obtained at the last time point of the study to assess immune correlates using IFNγ ELISPOT and cytokine Luminex® assays. Compared with Mock, HTI-vaccinated mice were enriched in Clostridiales genera (Eubacterium xylanophilum group, Roseburia and Ruminococcus) known as primary contributors of anti-inflammatory metabolites, such as short-chain fatty acids. Such shift was observed after the first HTI dose and remained throughout the study follow-up (18 weeks). However, the enriched Clostridiales genera were different between feces and gut sections. The abundance of bacteria enriched in vaccinated animals positively correlated with HTI-specific T-cell responses and a set of pro-inflammatory cytokines, such as IL-6. This longitudinal analysis indicates that, in mice, T-cell vaccination may promote an increase in gut bacteria known to produce anti-inflammatory molecules, which in turn correlate with proinflammatory cytokines, suggesting an adaptation of the gut microbial milieu to T-cell-induced systemic inflammation.

The immunological interplay between vaccination and the intestinal microbiota

“…Only a few studies have investigated whether the administration of vaccines is associated with changes in the composition of the intestinal microbiota 12,[20][21][22][23][24][25][26] , and whether the changes induced by vaccination, in turn, influence vaccine immunogenicity 20 . These studies have reported inconsistent results.…”

“…A recent study using metagenomic sequencing, reported that the intramuscular administration of an inactivated and an mRNA SARS-CoV-2 vaccine was associated with lower bacterial diversity, an increase in the relative abundance of Bacteroides caccae and a decrease in the relative abundance of Clostridiales (Coprococcus comes, Dorea longicatena and Ruminococcus obeum) in the intestinal microbiota one month after vaccination 20 . Animal studies have also shown that the administration of vaccines can lead to changes in the intestinal microbiota: in mice, an increase in the relative abundance of Bacteroides has been reported after intramuscular vaccination with a Mycobacterium tuberculosis vaccine 25 and compared with mice vaccinated with a placebo, mice vaccinated intramuscularly with an HIV T-cell immunogen had a higher relative abundance of Clostridiales (Eubacterium xylanophilum, Roseburia and Ruminococcus) 26 . In rhesus macaques, the intradermal administration of a combined HIV-1 DNA/protein vaccine has been shown to lead to an increase in the Firmicutes/Bacteroidetes ratio and a decreased relative abundance of Prevotella, Alloprevotella, Bacteroides, Acetobacteroides, Falsiporphyromonas and Anaerocella.…”

“…Mice with low dietary fibre intake or microbial insufficiency were defective in producing pathogen-specific antibody responses, which could be restored by the intake of SCFAs 31 . As a further example, the abundance of the genus Roseburia, a butyrateproducer, has been positively correlated with circulating interleukin (IL)-27 levels and T cell responses to an HIV T cell vaccine 26 .…”

“…1). As an example, it has been hypothesised that vaccination with an HIV T cell vaccine leads to T helper 1 cell stimulation and increased levels of inflammation mediators, which might lead to an increase in the abundance of Roseburia in the intestinal microbiota 26 . If T cell responses play an important role in inducing changes in the microbiota after vaccination, a further potentially important vaccine which could change the composition of the intestinal microbiota, is Bacillus Calmette-Guérin (BCG) vaccine.…”

Human umbilical cord mesenchymal stem cells improve disease characterization of Sjogren's syndrome in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity

“…Enterorhabdus promotes LPS‐induced intestinal inflammation and dysbiosis in mice 39 . Eubacterium._xylanophilum_group is named as the main contributor of anti‐inflammatory metabolites such as short‐chain fatty acids 49 . Here, the relative abundance of Escherichia‐Shigella and Enterorhabdus in the gut microbiota of NOD mice injected with T cells co‐cultured with UC‐MSCs or UC‐MSCs‐exo was reduced, while the relative abundance of Eubacterium._xylanophilum_group was increased.…”