Protective Immunity against Respiratory Tract Challenge with Yersinia pestis in Mice Immunized with an Adenovirus‐Based Vaccine Vector Expressing V Antigen
1Department of Genetic Medicine and 2Belfer Gene Therapy Core Facility, Weill Medical College of Cornell University, New York, New York; 3Public Health Research Institute at the International Center for Public Health, Newark, New Jersey
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.
Received 3 August 2005; accepted 14 May 2006; electronically published 25 September 2006.
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Online publication date: 1-Apr-2008.
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Potential conflicts of interest: none reported.
Financial support: National Institutes of Health (grants U54 AI057158 and R01 AI 55844); Will Rogers Memorial Fund, Los Angeles, California; Robert A. Belfer (gift to support the development of an antibioterrorism vaccine).
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M.J.C. and J.L.B. contributed equally to this study.