Contribution of the Type 3 Secretion System to immunogenicity of a liveYersinia pseudotuberculosisplague vaccine

Abstract

AbstractThe causative agent of plague,Yersinia pestis, remains a treat for public health worldwide. In the perspective to develop effective and safe vaccines, we present here a derived version of ourY. pseudotuberculosisVTnF1 live attenuated vaccine candidate that lacks the pYV virulence plasmid coding for the Type 3 Secretion system (T3SS) and no antibiotic resistance cassettes. This strain, called VpYV-, was safe for immunodeficient mice, and thus can be considered as deeply attenuated. It still has tropism for lymphatic tissues (Peyer’s patches, Mesenteric lymph nodes) but hardly reaches the spleen and liver. It elicits IgG to the F1 antigen as efficiently as VTnF1 but less directed to other Yersinia antigens. A single oral dose induced 100% protection against bubonic and pneumonic forms of plague, but this protection decreased faster with time than that of VTnF1. In the same line, VpYV-was 30% less protective against a F1-negativeY. pestis, revealing that the tools encoded by pYV are mandatory to obtain a large spectrum protection. Finally, VTnF1 like theY. pestisvaccine EV76 can induce protection against co-infectedY. pestisrelying on ‘host iron nutritional immunity”, indicating a potential use as therapeutics of recent infection. In contrast VpYV-failed to do so, revealing an importance of the T3SS in this mechanism. Overall, VpYV- and its parental strain VTnF1 offer a choice between more attenuation and safety or vaccine performances. They give an alternative and may represent useful tools to prevent and treatY. pestisinfection in healthy or immunosuppressed individuals.