Effects of Live and Peptide-Based Antimicrobiota Vaccines on Ixodes ricinus Fitness, Microbiota, and Acquisition of Tick-Borne Pathogens

This study explored the effects of antimicrobiota vaccines on the acquisition of <i>Borrelia</i> and <i>Rickettsia</i>, and on the microbiota composition of <i>Ixodes ricinus</i> ticks. Using a murine model, we investigated the immunological responses to live <i>Staphylococcus epidermidis</i> and multi-antigenic peptide (MAP) vaccines. Immunized mice were infected with either <i>Borrelia afzelii</i> or <i>Rickettsia helvetica</i>, and subsequently infested with pathogen-free <i>I. ricinus</i> nymphs. We monitored the tick feeding behavior, survival rates, and infection levels. Additionally, we employed comprehensive microbiota analyses, including the alpha and beta diversity assessments and microbial co-occurrence network construction. Our results indicate that both live <i>S. epidermidis</i> and MAP vaccines elicited significant antibody responses in mice, with notable bactericidal effects against <i>S. epidermidis</i>. The vaccination altered the feeding patterns and fitness of the ticks, with the Live vaccine group showing a higher weight and faster feeding time. Microbiota analysis revealed significant shifts in the beta diversity between vaccine groups, with distinct microbial networks and taxa abundances observed. Notably, the MAP vaccine group exhibited a more robust and complex network structure, while the Live vaccine group demonstrated resilience to microbial perturbations. However, the effects of antimicrobiota vaccination on <i>Borrelia</i> acquisition appeared taxon-dependent, as inferred from our results and previous findings on microbiota-driven pathogen refractoriness. <i>Staphylococcus</i>-based vaccines altered the microbiota composition but had no effect on <i>B. afzelii</i> infection, and yielded inconclusive results for <i>R. helvetica</i>. In contrast, previous studies suggest that <i>E. coli</i>-based microbiota modulation can induce a pathogen-refractory state, highlighting the importance of both bacterial species and peptide selection in shaping microbiota-driven pathogen susceptibility. However, a direct comparison under identical experimental conditions across multiple taxa is required to confirm this taxon-specific effect. These findings suggest that antimicrobiota vaccination influences tick fitness and microbiota assembly, but its effects on pathogen transmission depend on the bacterial taxon targeted and the selected peptide epitopes. This research provides insights into the need for strategic bacterial taxon selection to enhance vaccine efficacy in controlling tick-borne diseases.