Attenuated Salmonella vaccine as a vector for heterologous antigens

Abstract

Salmonella enterica, serotype Typhi, is the causing agent of typhoid fever, a disease that affects the inhabitants of the poorest areas in the world. Many researchers have focused their attention on its fascinating cell invasion mechanisms, intracellular multiplication and bacterial intercellular dissemination expressed in vivo and in vitro. Although the above mechanisms are directly associated with pathogenicity and disease severity, defined mutations in the Salmonella chromosome have allowed the use of these virulence mechanisms in benefit of the mammalian host. Attenuated Salmonella mutants are still able to invade M cells of the intestinal mucosa and to migrate to the lymphoid cells of the reticuloendothelial system. Once inside the host, the attenuated Salmonella is unable to cause disease, instead. it effectively activates the humoral and cellular immune responses not only towards the Salmonella antigens themselves but also to the recombinant heterologous antigens being expressed and delivered by the bacteria. In the present review, recent advances in the field of live attenuated Salmonella vaccines will be discussed; the preclinical and clinical data will be evaluated, and the clinical application as antigen delivery systerns will be anticipated. lnformation will be given on current molecular biology techniques on cloning and prokaryotic expression of tetanus, diphtheria and pertussis toxins, as well as Helicobacterpylori and Plasmodium falciparum antigens. Similarly, the use of attenuated Salmonella as a vector for DNA vaccine delivery and further eukaryotic expression of recornbinant antigens will be proposed. Continuous scientific and technological efforts in the field of vaccination with live attenuated vectors suggest that Salmonella is a promising weapon to face the challenge irnposed by typhoid fever. Similarly, preclinical and phase I clinical studies indicate how efficient lisve attenuated Salrnonella vaccines may be as a delivery systern for heterologous antigens. More phase II and phase III clinical studies will be necessarv to demonstrate that Salmonella vectors may be part of the vaccine arsenal capable of protecting the world population against the constant risk of infectious diseases due to emergent and re-emergent microorganisms.