The potential application of Yersinia pestis for bioterrorism emphasizes the urgent need to develop more effective vaccines against airborne infection. The current status of plague vaccines has been reviewed. The present emphasis is on subunit vaccines based on the F1 and LcrV antigens. These provide good protection in animal models but may not protect against F1 strains with modifications to the type III secretion system. The duration of protection against pneumonic infection is also uncertain. Other strategies under investigation include defined live-attenuated vaccines, DNA vaccines, mucosal delivery systems and heterologous immunization. The live-attenuated strain Y. pestis EV NIIEG protects against aerosol challenge in animal models and, with further modification to reduce residual virulence and to optimize respiratory protection, it could provide a shortcut to improved vaccines. The regulatory problems inherent in licensing vaccines for which efficacy data are unavailable and their possible solutions are discussed herein.

In response to the epidemiological situation, live attenuated or killed vaccines against anthrax, brucellosis, cholera, glanders, plague and tularemia were developed and used for immunization of at...

Despite many decades of intensive studies of Yersinia pestis, the causative agent of plague, there is no safe and efficient vaccine against this devastating disease. A recently developed F1/V subun...

Yersinia pestisundergoes an obligate flea–rodent–flea enzootic life cycle. The rapidly fatal properties ofY. pestisare responsible for the organism's sustained survival in natural plague foci. Lipopolysaccharide (LPS) plays several roles inY. pestispathogenesis, prominent among them being resistance to host immune effectors and induction of a septic-shock state during the terminal phases of infection. LPS is acylated with 4–6 fatty acids, the number varying with growth temperature and affecting the molecule's toxic properties.Y. pestismutants were constructed with a deletion insertion in thelpxMgene in both virulent and attenuated strains, preventing the organisms from synthesizing the most toxic hexa-acylated lipid A molecule when grown at 25 °C. The virulence and/or protective potency of pathogenic and attenuatedY. pestisΔlpxMmutants were then examined in a mouse model. The ΔlpxMmutation in a virulent strain led to no change in the LD₅₀value compared to that of the parental strain, while the ΔlpxMmutation in attenuated strains led to a modest 2.5–16-fold reduction in virulence. LPS preparations containing fully hexa-acylated lipid A were ten times more toxic in actinomycin D-treated mice then preparations lacking this lipid A isoform, although this was not significant (P>0.05). The ΔlpxMmutation in vaccine strain EV caused a significant increase in its protective potency. These studies suggest there is little impact from lipid A modifications on the virulence ofY. pestisstrains but there are potential improvements in the protective properties in attenuated vaccine strains.

Deletion mutants in the lpxM gene in two Yersinia pestis strains, the live Russian vaccine strain EV NIIEG and a fully virulent strain, 231, synthesise a less toxic penta-acylated lipopolysaccharide (LPS). Analysis of these mutants revealed they possessed marked reductions in expression and immunoreactivity of numerous major proteins and carbohydrate antigens, including F1, Pla, Ymt, V antigen, LPS, and ECA. Moreover, both mutants demonstrated altered epitope specificities of the antigens as determined in immunodot-ELISAs and immunoblotting analyses using a panel of monoclonal antibodies. The strains also differed in their susceptibility to the diagnostic plague bacteriophage L-413C. These findings indicate that the effects of the lpxM mutation on reduced virulence and enhanced immunity of the Y. pestis EV DeltalpxM is also associated with these pleiotropic changes and not just to changes in the lipid A acylation.