N255 is a key residue for recognition by a monoclonal antibody which protects against Yersinia pestis infection

Hill, Jim; Leary, Sophie E.C.; Smither, Sophie J.; Best, Angus; Pettersson, Jonas; Försberg, Åke; Lingard, Bry; Lipka, Alexandria; Brown, Katherine A.; Williamson, E. Diane; Titball, Richard W.

doi:10.1016/j.vaccine.2009.09.061

Cited by 21 publications

(21 citation statements)

References 32 publications

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“…Furthermore, at least one protective B cell epitope identified in V-antigen fitted into the proposed pentameric structure for V-antigen on the tip of the injectisome [59].…”

Section: Virulence Factors As Immunogensmentioning

confidence: 88%

Protecting against plague: towards a next-generation vaccine

Williamson

Oyston

2013

Clinical and Experimental Immunology

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SummaryThe causative organism of plague is the bacterium Yersinia pestis. Advances in understanding the complex pathogenesis of plague infection have led to the identification of the F1-and V-antigens as key components of a nextgeneration vaccine for plague, which have the potential to be effective against all forms of the disease. Here we review the roles of F1-and V-antigens in the context of the range of virulence mechanisms deployed by Y. pestis, in order to develop a greater understanding of the protective immune responses required to protect against plague.

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“…Furthermore, at least one protective B cell epitope identified in V-antigen fitted into the proposed pentameric structure for V-antigen on the tip of the injectisome [59].…”

Section: Virulence Factors As Immunogensmentioning

confidence: 88%

Protecting against plague: towards a next-generation vaccine

Williamson

Oyston

2013

Clinical and Experimental Immunology

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“…rV10-2 specific IgG responses in human volunteers could then be analyzed for the attributes of protecting passively immunized mice against lethal plague challenge or of blocking Y. pestis type III injection of macrophages [25, 49, 59]. In conjunction with vaccine efficacy trials using both rodents and NHPs, for example guinea pigs and AGM, these assays may be useful as correlates for protective immunity against plague in humans.…”

Section: Discussionmentioning

confidence: 99%

Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

Quenee

Ciletti

Elli

et al. 2011

Vaccine

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Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271–300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing.

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“…pestis-induced apoptosis of J774A.1 macrophages as a measure for type III injection of effector Yops. Earlier work demonstrated that Y. pestis injection of effector Yops into macrophages induces apoptosis, which serves as a quantifiable measure for protein transport via the type III pathway (28). After infection of mouse J774.1 macrophages with Y. enterocolitica or Y. pestis strains, the cultures were incubated with propidium iodide to distinguish live cells from apoptotic remnants.…”

Section: Anti-rv10 Andmentioning

confidence: 99%