Generation of vaccine strains of gram-negative bacteria with reduced adverse reactions

The main shortcoming of the modem live and killed vaccines based on gram-negative bacterial strains is their ability to cause adverse reactions. The majority of the adverse reactions are associated with the effect of biological activity of lipopolysaccharide. The report covers the problems concerned with biogenesis of the lipid A, lipopolysaccharide structural component, responsible for its endotoxic activity, as well as with genes determining lipid A synthesis. The special attention is paid to gene-engineering technique for reduction of adverse reactions of vaccine strains that are based on the knock-out mutagenesis of genes waaM and/or waaN responsible for addition of lauroyl and myristoyl residues to the distal glucosamine unit lipid A, generating acyloxyacyl moieties.