Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates.

The development of safe, efficacious recombinant attenuated bacterial antigen delivery systems requires attention to some desired attributes. The vaccine design should be focused on—enhancing immunogenicity and the magnitude and duration of the immune response to the expressed protective antigen, and on diminishing the potentially competing immune responses to antigens of the attenuated bacterial antigen delivery vector. Depending upon the disease to be prevented and the nature of the pathogen causing that disease—it may be necessary to make genetic modifications of the antigen delivery system, to maximize a Th2 response important for inducing mucosal and systemic antibody responses or, in other cases, a Th1 response to enhance the cellular immunity. It is potentially desirable to introduce biological containment features into vaccines to prevent their survival and persistence in environments into which they might be introduced as a consequence of immunization. The magnitude of protective immunity to an expressed protective antigen in regard to mucosal and systemic antibody responses, is more or less dependent on the amount of protective antigen delivered to the immunized host.

Chapter 56 – Antigen Delivery Systems II: Development of Live Recombinant Attenuated Bacterial Antigen and DNA Vaccine Delivery Vector Vaccines

Phenotype, virulence and immunogenicity of Edwardsiella ictaluri cyclic adenosine 3',5'-monophosphate receptor protein (Crp) mutants in catfish host.

Salmonella has been employed to deliver therapeutic molecules against cancer and infectious diseases. As the carrier for target gene(s), the cargo plasmid should be stable in the bacterial vector. Plasmid recombination has been reduced in E. coli by mutating several genes including the recA, recE, recF and recJ. However, to our knowledge, there have been no published studies of the effect of these or any other genes that play a role in plasmid recombination in Salmonella enterica. The effect of recA, recF and recJ deletions on DNA recombination was examined in three serotypes of Salmonella enterica. We found that (1) intraplasmid recombination between direct duplications was RecF-independent in Typhimurium and Paratyphi A, but could be significantly reduced in Typhi by a ΔrecA or ΔrecF mutation; (2) in all three Salmonella serotypes, both ΔrecA and ΔrecF mutations reduced intraplasmid recombination when a 1041 bp intervening sequence was present between the duplications; (3) ΔrecA and ΔrecF mutations resulted in lower frequencies of interplasmid recombination in Typhimurium and Paratyphi A, but not in Typhi; (4) in some cases, a ΔrecJ mutation could reduce plasmid recombination but was less effective than ΔrecA and ΔrecF mutations. We also examined chromosome-related recombination. The frequencies of intrachromosomal recombination and plasmid integration into the chromosome were 2 and 3 logs lower than plasmid recombination frequencies in Rec+ strains. A ΔrecA mutation reduced both intrachromosomal recombination and plasmid integration frequencies. The ΔrecA and ΔrecF mutations can reduce plasmid recombination frequencies in Salmonella enterica, but the effect can vary between serovars. This information will be useful for developing Salmonella delivery vectors able to stably maintain plasmid cargoes for vaccine development and gene therapy.

/pdf/improving-salmonella-vector-with-rec-mutation-to-stabilize-2yo6xhk1ch.pdf

Improving Salmonella vector with rec mutation to stabilize the DNA cargoes

Attenuated Strains of Salmonella enterica Serovars Typhi and Paratyphi as Live Oral Vaccines Against Enteric Fever

Bacteremia Associated with Live Attenuated χ8110 Salmonella enterica serovar Typhi ISP1820 in Healthy Adult Volunteers

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Bacteremia Associated with Live Attenuated χ8110 Salmonella enterica serovar Typhi ISP1820 in Healthy Adult Volunteers