Yersinia outer proteins (YOPS) E, K and N are antigenic but non-protectivecompared to V antigen, in a murine model of bubonic plague

The pathogenic Yersiniae produce a range of virulence proteins, encoded by a 70 kb plasmid, which are essential for infection, and also form part of a contact-dependent virulence mechanism. One of these proteins, V antigen, h as been shown to confer a high level of protection against parenteral infec tion with Y: pestis in murine models, and is considered to be a protective antigen. In this study, the protective efficacy of V antigen has been compa red in the same model with that of other proteins (YopE, YopK and YopN), wh ich are part of the contact-dependent virulence mechanism. Mice immunised w ith two intraperitoneal doses of V antigen or each of the Yops, administere d with either Alhydrogel or interleukin-12, produced high antigen-specific serum IgG titres. As shown in previous studies, V+Alhydrogel was fully prot ective, and 5/5 mice survived a subcutaneous challenge with 90 or 9 x 10(3) LD50's of Y. pestis GB. In addition, these preliminary studies also showed that V + IL-12 was partially protective: 4/5 or 3/5 mice survived a challe nge with 90 or 9 x 10(3) LD50's, respectively. In contrast, none of the mic e immunised with the Yops survived the challenges, and there was no signifi cant delay in the mean time to death compared to mice receiving a control p rotein. These results show that using two different vaccine regimens Yops E , K and N, failed to elicit protective immune responses in a murine model o f plague, whereas under the same conditions, V antigen was fully or partial ly protective. (C) 1999 Academic Press.