Development of vaccinia virus based reservoir-targeted vaccines.
Abstract: One of
the strategies to control vector-borne diseases is to eradicate or limit the causative
agent from its zoonotic reservoir. We have developed reservoir-targeted oral vaccines
against two diseases: plague and Lyme disease. We have used vaccinia virus (VV) as the
vector for delivery of the vaccine antigens. The plague vaccine is a recombinant VV
expressing F1-V fusion antigen of ... read moreYersinia pestis. A single dose of the vaccine
generates a strong immunogenic response in mice and confers long-term protection against
a lethal challenge of Y. pestis. The Lyme vaccine is a recombinant VV expressing
Borrelia burgdorferi OspA antigen and was previously shown to be effective in protecting
C3H mice against B. burgdorferi -infected tick bite. Here, we have shown development of
an effective bait formulation to deliver the vaccine in the environment. The stability
of the vaccine in the bait formulation was tested under simulated environmental
conditions. We have shown that the VV-ospA baited vaccine is efficacious in protecting
Peromyscus mice against a bite by an infected tick bite. Also, the vaccine is effective
in decreasing acquisition of B. burgdorferi by uninfected larval ticks after feeding on
infected mice. Further, we have used a live, in vivo imaging technology to determine the
localization and distribution of VV in mice after oral infection via gavage
administration and bait feeding. Using the in vivo imaging technology, we have attempted
to optimize the bait composition for increased uptake of the virus during feeding. In
summary, we have developed orally deliverable baited vaccines against two vector-borne
pathogens with the aim of reducing infection in animal reservoirs that in turn will
reduce the number of human cases. The vaccines may be an important part of an integrated
management program to reduce the incidence of plague and Lyme
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Molecular Microbiology.
Advisor: Linden Hu.
Committee: Joan Mecsas, Andrew Camilli, Abraham Sonenshein, and Utpal Pal.
Keywords: Molecular biology, and Microbiology.read less