MUCOSAL IMMUNIZATION AGAINST PLAGUE
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Date
1999-06
Type of Work
Department
Hood College Biology
Program
Biomedical and Environmental Science
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Abstract
Yersinia pestis is the causative agent of plague. There are two forms of the disease,
the bubonic and the pneumonic form. The bubonic form can be acquired by humans from
the bite of an infected flea which can lead to the pneumonic form where aerosol
transmission between humans is highly fatal. There are two vaccines (USP and EV76)
currently in use throughout the world and both have serious limitations. The USP vaccine
is a formalin-killed whole-cell preparation. Unfortunately this vaccine does not seem to
protect against the pneumonic form of the disease. The EV76 preparation is a live
attenuated vaccine which has been associated with high reactogenicity.
The Low Calcium Response Virulence (LcrV) antigen of Y. pestis is a promising
candidate antigen. In this study the LcrV antigen was genetically fused to the N-terminus
of cholera toxin A subunit (CtxA) (MTD672) or to the A2 peptide of CtxA (MTD669).
These fusion proteins were co-expressed with the B subunit of cholera toxin (CtxB) in
Escherichia coli to form a functional chimeric holotoxin. The resulting holotoxins were
purified and characterized. Both chimeras retained their ability to bind to Gm ganglioside
and to cross react with polyclonal antiserum to LcrV and to Ctx. The chimeras were
assessed for their immunogenicity in mice by both the intraperitoneal and intranasal routes
of immunization. The results indicate that the chimeras were able to elicit IgG antibody in
the serum and the lung by both routes of immunization. Attempts to assess the ability of
these vaccine candidates to protect mice against aerosol challenge with Y. pestis were
thwarted by the failure of the positive control group to survive challenge.