Coming of AGE: facile generation of attenuated vaccine strains through heterologous gene expression

Abstract

Live attenuated vaccine strains for bacterial pathogens are conventionally constructed by inactivating genes important for virulence or metabolism to render the organism less virulent. Ideally, these strains follow a natural route of infection, yet elicit an immune response without causing disease. In particular, live attenuated vaccines often have the advantage of generating cellular immune responses that killed organisms and purified antigens fail to stimulate. Importantly, a fine balance between attenuation and sufficient persistence in the host must be achieved in order to produce a protective and durable immune response. Unfortunately, the reality is that, in most cases, the complete repertoire of factors responsible for virulence is unknown or not well understood, hindering the creation of attenuated vaccine strains. Thus, the generation of live attenuated vaccines would be greatly facilitated by novel, portable approaches for attenuating Gram-negative pathogens.