Polymorphisms in the lcrV Gene of Yersinia enterocolitica and Their Effect on Plague Protective Immunity

ABSTRACT Current efforts to develop plague vaccines focus on LcrV, a polypeptide that resides at the tip of type III secretion needles. LcrV-specific antibodies block Yersinia pestis type III injection of Yop effectors into host immune cells, thereby enabling phagocytes to kill the invading pathogen. Earlier work reported that antibodies against Y. pestis LcrV cannot block type III injection by Yersinia enterocolitica strains and suggested that lcrV polymorphisms may provide for escape from LcrV-mediated plague immunity. We show here that polyclonal or monoclonal antibodies raised against Y. pestis KIM D27 LcrV (LcrV D27 ) bind LcrV from Y. enterocolitica O:9 strain W22703 (LcrV W22703 ) or O:8 strain WA-314 (LcrV WA-314 ) but are otherwise unable to block type III injection by Y. enterocolitica strains. Replacing the lcrV gene on the pCD1 virulence plasmid of Y. pestis KIM D27 with either lcrV W22703 or lcrV WA-314 does not affect the ability of plague bacteria to secrete proteins via the type III pathway, to inject Yops into macrophages, or to cause lethal plague infections in mice. LcrV D27 -specific antibodies blocked type III injection by Y. pestis expressing lcrV W22703 or lcrV WA-314 and protected mice against intravenous lethal plague challenge with these strains. Thus, although antibodies raised against LcrV D27 are unable to block the type III injection of Y. enterocolitica strains, expression of lcrV W22703 or lcrV WA-314 in Y. pestis did not allow these strains to escape LcrV-mediated plague protective immunity in the intravenous challenge model.