Konstrukcja szczepionek podjednostkowych z wykorzystaniem komórek Salmonella enterica jako nośnika heterologicznych genów
1. Salmonella jako idealny nośnik heterologicznych antygenów. 2. Atenuacja komórek S.enterica. 3. Stabilność utrzymania transgenu. 4. Poziom ekspresji transgenu. 5. Lokalizacja antygenu a typ odpowiedzi immunologicznej. 6. Podsumowanie
Abstract: Salmonella enterica strains are widely employed as a live delivery vector for subunit vaccine construction. Vaccine strains must be safe but still immunogenic; therefore, it is crucial to obtain a proper balance between the attenuation and the reactogenicity of the constructed strains. Salmonella strains used in immunoprophylaxis are mainly constitutively disrupted in genes involved in auxotrophy, virulence or regulation. A novel promising concept of the Salmonella-based vaccine design is a regulated delayed attenuation in vivo combined with a delayed antigen expression system. Using this approach bacteria display features of a wild-type strain at the time of oral vaccination to effectively colonize the lymphoid tissue and the fully attenuated phenotype after host tissue colonization. Expression of heterelogous genes in Salmonella cells is mainly achieved by introducing recombinant plasmids harboring gene of interest. Alternatively, a transgene can be integrated into a chromosomal DNA. Diverse strategies were developed to control plasmid maintenance and foreign gene expression. Among them the most frequently used are the balanced-lethal and toxin-antidote systems or operator-repressor titration technology. Overproduction of a recombinant protein often causes a metabolic burden in vaccine cells resulting in the loss of their viability. To overwhelm the problem, the transgene expression is kept under control of an in vivo inducible promoter or a promoter which activity is regulated by appropriate small molecules. Alternatively, plasmids with a regulated copy number or a delayed antigen synthesis system have been employed by various research groups. Localization of an antigen in a carrier cell is also critical for the strength and type of immune response. A programmed lysis of carrier cells is used to deliver the antigen to host immune cells. Moreover, Salmonella is used to carry DNA vaccines. Here, we review the latest strategies in the design of Salmonella-based subunit vaccines.
1. Salmonella as a perfect carrier of heterologous antigens. 2. Attenuation of S.enterica cells. 3. Transgene stability. 4. Transgene expression level. 5. Antigen localization and the type of immune response. 6. Conclusions