Can a 'flawless' live vector vaccine strain be engineered?

The efficiency of any live bacterial vector vaccine hinges on its ability to present sufficient foreign antigen to the human immune system to initiate the desired protective immune response(s). However, synthesis of sufficient levels of heterologous antigen can result in an increase in metabolic burden with an accompanying decrease in the fitness of the live vector, which can ultimately lower desired immune responses to both live vector and heterologous antigen. Here, we explore the underlying mechanisms of metabolic load and propose ways of minimizing such burdens to enhance the fitness and immunogenicity of Salmonella-based live vector vaccines.