Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens

Abstract

A variety of techniques, including the use of live oral vaccines, have been used to deliver antigens to the gut-associated lymphoid tissues in an attempt to initiate production of specific secretory immunoglobulin A for protection against pathogens that colonize or cross mucosal surfaces to initiate infection. A number of attenuated Salmonella mutants are able to interact with the lymphoid tissues in the Peyer's patches but are not able to cause systemic disease. Some of these mutants are effective as live vaccines (i.e., able to protect against infection with the virulent Salmonella parent) and are candidates for use as carriers for virulence determinants of other mucosal pathogens. This has been shown to be an effective means of stimulating significant levels of specific mucosal secretory immunoglobulin A directed against the carrier strains and against a variety of heterologous antigens and has been shown to stimulate production of serum antibodies and cell-mediated responses as well. This review examines the history of this mechanism of vaccine delivery and summarizes the most recent applications of this evolving technology. This is a technique for vaccine delivery with significant potential for influencing the management of infectious diseases on a large scale. It can be used not only for vaccines against enteric bacterial pathogens but also for vaccines against a variety of other bacteria, viruses, and parasites. The results obtained to date are encouraging, and there is great potential for development of safe, effective, affordable vaccines.

Cancer immunotherapy based on recombinant Salmonella enterica serovar Typhimurium aroA strains secreting prostate-specific antigen and cholera toxin subunit B

“…[34][35][36] In this context, it is widely known that bacterial carriers, especially Salmonella spp. can induce potent, protective humoral and cellular immune responses against the heterologous antigens 37,38 and can activate the components of the innate immune system. [39][40][41] This knowledge explains why bacteria like Salmonella represent promising vectors for delivery of tumor antigens.…”

Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment

“…The objective of this study was to construct and evaluate a biological containment system that would be consistent with the requirements for efficacious vaccination, in particular, colonization of host lymphoid tissues for an amount of time sufficient for optimal antigen delivery. RASV are capable of delivering a variety of bacterial, viral, fungal, and parasitic antigens, thereby eliciting humoral and cellular immunity in the immunized host (1,(34)(35)(36). Immune responses, especially antibody responses, are enhanced when the antigen is released into the extracellular environment as opposed to being sequestered in the bacterial cytoplasm (11,12).…”

“…A variety of attenuating mutations (reviewed in refs. 1 and 2) and antibiotic-free balancedlethal plasmid stabilization systems has been developed for this purpose (1,(3)(4)(5). However, biological containment systems are required to address the potential risk posed by the unintentional release of these genetically modified organisms into the environment, a subject of considerable concern (6,7).…”

“…L ive attenuated pathogens, such as Salmonella enterica, have been developed as homologous vaccines and as carriers of heterologous antigens because of their capacity for efficient mucosal antigen delivery (1,2). A variety of attenuating mutations (reviewed in refs.…”

The Vaccine Potential of Heat-killed Attenuated Strain of <i>Salmonella</i>

“…Salmonella strains induce strong local and systemic immune responses, as well as cellular responses, and a live attenuated strain of Salmonella has been evaluated as a potential oral vaccine or vaccine vector for delivery of recombinantly expressed foreign Ags (2)(3)(4). Attenuation has focused on strains mutated in the aro genes, which encode enzymes of the pre-chorismate metabolic pathway that are involved in aromatic compound biosynthesis (5,6).…”