Live attenuated bacterial vaccines: new approaches for safety and efficacy.

Problems arising from reversion to virulence in genetically attenuated bacterial vaccines can be overcome by the combination, in one strain, of multiple temperature-sensitive mutations of identical phenotype. Immunogenicity of attenuated strains may be enhanced by incorporation of mutations which permit limited replication in the vaccinee (thereby increasing antigen mass while minimising the possibility of vaccine reactions) and the expression of genes coding for antigens which are synthesised only during infection of the host.