Use of Genetically Modified Bacteria to Modulate Adaptive Immunity

Abstract

Infectious diseases caused by virulent bacteria are a significant cause of morbidity and mortality worldwide, especially in developing countries. However, attenuated strains derived from pathogenic bacteria, such as Salmonella, are highly immunogenic and can be used as vaccines to promote immunity against parental pathogenic bacteria strains. Further, they can be genetically manipulated to either express foreign antigens or deliver exogenous DNA, in order to induce immunity against other pathogens or antigens. Contrarily, specific structural modifications in attenuated Salmonella have allowed the generation of strains that can be well tolerated by the immune system and reduce inflammatory responses. It is thought that those strains could be considered as vectors to promote specific immune tolerance for certain auto-antigens or allergens and reduce unwanted or self-reactive immune responses. In addition, some structural features of Salmonella can contribute to defining the nature and type of polarization of the adaptive immune response induced after immunization, which can be considered as a tool to modulate antigen-specific immunity. In this article we discuss recent advances in the understanding of immune system modulation by molecular components of bacteria and their exploitation for the rational induction of pathogen immunity or antigen-specific tolerance.

Concomitant Tumor and Autoantigen Vaccination Supports Renal Cell Carcinoma Rejection

“…However, whereas we and other groups (24-26) did not observe a response against the eukaryotic vector, SLs themselves are immunogenic (58) and are prone to deviating an immune response toward immunosuppression in favor of their survival (59). Although the latter feature is largely circumvented by using a eukaryotic expression vector (23), we noted a slight upregulation of IL-1b, IL-10, and MDSC in SL-fed mice.…”

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

“…Because of its importance, several viruses have evolved molecular mechanisms to impair T-cell activation and gain advantage over the host immune response to disseminate within infected tissues. 33,38 Given that DCs play a major role in naive T-cell priming, several pathogens have evolved molecular mechanisms to impair the function of DCs. 10,31,39 A recent study using antigen-specific mouse T cells showed that conventional DCs isolated from hMPVinfected lungs fail to induce the proliferation of pOVAspecific DO11.10 T cells.…”

Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines

“…An optimal live oral Salmonella vaccine would retain its ability to colonize and invade host lymphoid tissues while remaining completely avirulent [4]. Several Salmonella strains with various modifications have been created in an attempt to balance safety and immunogenicity (see reviews [1, 3, 5]), however, there is a need for improved strains.…”