In Animal Model, New Vaccine Protects from Pneumonic Plague

In a new study, researchers from the University of Chicago in Illinois and the Lovelace Biomedical and Environmental Research Institute in Albuquerque, N.M., developed a vaccine incorporating the protein V10 and found that it protected macaques from lethal pneumonic plague and may have implications for use in humans. They report their findings in the December 2008 issue of the journal Infection and Immunity.

Yersinia pestis is the causative agent of pneumonic plague infections in humans. Recent wildlife studies indicate that plague is rampant among rodent populations in the southwestern United States, Southeast Asia, Eastern Europe, central and southern Africa as well as South America where humans are highly susceptible to infection. The potential for large-scale human infections as well as continuously emerging antibiotic-resistant strains of Y. pestis reinforces the need for an effective vaccine.

Currently, antiplague subunit vaccines in development for human use contain recombinant low-calcium-response V antigens (rLcrV) and recombinant F1 (rF1) antigens either in equal amounts or as a fusion protein (rF1-rLcrV). In the study the researchers immunized cynomolgus macaques with an aerosol vaccine incorporating a variant of the rLcrV protein, recombinant V10 (rV10) and challenged them with a lethal dose of pneumonic plague. Results showed that rV10 prevented infection and displayed equally protective immunity to vaccines containing rLcrV or rLcrV plus rF1. Further studies showed that some antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, conferred protection in mice challenged with bubonic plague.

"Here, we show that immunization with either purified rLerV (a protein at the tip of type III needles) or a variant of this protein, recombinant V10 (rV10) (lacking amino acid residues 271 to 300), alone or in combination with rF1, prevented pneumonic lesions and disease pathogenesis," say the researchers.

Reference: C.A. Cornelius, L.E. Quenee, K.A. Overheim, F. Koster, T.L. Brasel, D. Elli, N.A. Ciletti, O. Schneewind. 2008. Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague. Infection and Immunity. 76. 12: 5588-5597.