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 boost 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) to C57Bl/6 mice following a heterologous prime-boost scheme. The longitudinal dynamics of the mice gut microbiota were characterized by 16S ribosomal RNA sequencing in fecal samples collected from cages, as well as from three gut sections (caecum, small and large intestine). Serum and spleen cells were obtained at the study endpoint to assess immune correlates using IFNγ ELISPOT and cytokine Luminex® assays. Compared with PBS, HTI vaccination increased several Clostridiales genera associated with anti-inflammatory responses, such as Eubacterium xylanophilum group, Roseburia and Ruminococcus. Such shifts were observed after the first HTI dose and remained throughout the study follow-up (18 weeks). Hoverer, the specifically enriched Clostridiales genera were different between feces and gut sections. The abundance of HTI-enriched bacteria positively correlated with the magnitude of vaccine-induced responses and a set of pro-inflammatory cytokines, especially IL-6. This longitudinal analysis reveals that, in mice, T-cell vaccination promotes the increase of anti-inflammatory gut bacteria in parallel to significant associations with proinflammatory cytokines, suggesting an adaptation of the gut microbial milieu to T-cell-induced systemic inflammation.