Saudi Cultural Missions Theses & Dissertations
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Item Restricted Immunity and protection induced by outer membrane vesicles against Invasive non-Typhoidal Salmonella(University of Birmingham, 2024-05-24) Alshayea, Areej; Cunningham, AdamSalmonella enterica is responsible for causing both diarrheal and systemic illnesses, which remain significant global concerns. The development of vaccines that offer broad protection against multiple serovars holds potential in effectively managing diseases caused by Salmonella. Outer Membrane Vesicles (OMVs), which are naturally released by Gram-negative bacteria, show promising potential for developing subunit vaccines due to their high immunogenicity and protective effectiveness. The O-antigen of lipopolysaccharide (LPS) has been identified as a key target for inducing protective immunity. However, variation in O-antigen expression between closely related pathogens, such as S. Typhimurium and S. Enteritidis, limits cross-protection after natural infection. Modifications in the O-antigen chain length can alter outer membrane structure and composition. In this study, genetic mutations were introduced into Salmonella OMV-producing strains in order to reduce or delete LPS O-antigen expressions. The cellular, humoral, and functional immune responses to OMV from S. Typhimurium expressing wild-type length O-antigens (WT-OMV), ≤1 O-antigen repeat (wzy-OMV), or no O-antigen (wbaP-OMV) were assessed in mice immunisation studies. All OMV induced similar plasma cell and germinal centre responses, although the nature and outcomes of these responses differed. Surprisingly, wzy-OMV elicited comparable levels of anti-LPS IgG responses to WT-OMV. However, wzy-OMV and wbaP-OMV induced more robust responses against cell-surface-exposed porin proteins and cross-reactive antibodies targeting S. Enteritidis. Immunisation with wzy-OMV provided protection against S. Typhimurium comparable to that induced by WT-OMV. In contrast, after one immunisation, with any OMV type, there was minimal control of S. Enteritidis infections, except in the blood. However, after boosting with OMVs, there was an enhanced level of cross-protection.4 0