The aerosol form of the bacterium Yersinia pestis causes the pneumonic plague, a 
rapidly fatal disease. At present, no plague vaccines are available for use in 
the United States. One candidate for the development of a subunit vaccine is the 
Y. pestis virulence (V) antigen, a protein that mediates the function of the 
Yersinia outer protein virulence factors and suppresses inflammatory responses 
in the host. On the basis of the knowledge that adenovirus (Ad) gene-transfer 
vectors act as adjuvants in eliciting host immunity against the transgene they 
carry, we tested the hypothesis that a single administration of a 
replication-defective Ad gene-transfer vector encoding the Y. pestis V antigen 
(AdsecV) could stimulate strong protective immune responses without a 
requirement for repeat administration. AdsecV elicited specific T cell responses 
and high IgG titers in serum within 2 weeks after a single intramuscular 
immunization. Importantly, the mice were protected from a lethal intranasal 
challenge of Y. pestis CO92 from 4 weeks up to 6 months after immunization with 
a single intramuscular dose of AdsecV. These observations suggest that an Ad 
gene-transfer vector expressing V antigen is a candidate for development of an 
effective anti-plague vaccine.