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Theresa Trunkle, Xinghong Yang, Catherine M Bosio, David W Pascual, Co-Expression of Yersinia pestis F1- and V-Ags by the Same Salmonella Vaccine Protects Against Nasal Y. pestis Challenge (41.14), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Page S32, https://doi.org/10.4049/jimmunol.178.Supp.41.14
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Abstract
To test whether the protective antigens (Ags) to Yersinia pestis can be simultaneously delivered, the Y. pestis cafI operon encoding the F1 Ag, and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vector. F1-Ag expression was controlled under its endogenous promoter from the cafI operon and amply expressed; a chimeric promoter consisting of ptetS and pphoP in the pV55 plasmid showed enhanced V-Ag expression. Immunofluorescence data showed that the single construct, Salmonella-(F1-V)Ags, could co-express both Ags. When orally tested, the Salmonella-(F1-V)Ags vaccine elicited elevated Ab titers to both F1- and V-Ags. Supportive CD4+ T cell responses showed that IFN-γ was elevated in response to F1-Ag restimulation and to a lesser degree, IL-4 and IL-13. V-Ag restimulation showed much less IFN-γ and IL-4 production. IL-10 responses were equivalent to both Ags. IgG1 and IgG2a subclass responses to both Ags were equivalent. Upon nasal challenge, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1-V)Ags protected against 100 LD50 Y. pestis, but mice immunized with Salmonella constructs bearing a single Ag showed impaired efficacies. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect immune protection against Y. pestis.
This work is supported by AI-56286 and NIH 1U54 AI-06537.
