Protective Immunity Against Respiratory Tract Challenge With Yersinia Pestis in Mice Immunized With an Adenovirus-Based Vaccine Vector Expressing V Antigen

J Infect Dis. 2006 Nov 1;194(9):1249-57. doi: 10.1086/507644. Epub 2006 Sep 25.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / metabolism*
  • Animals
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • Mice
  • Plague / prevention & control*
  • Plague Vaccine / immunology*
  • Pore Forming Cytotoxic Proteins / immunology*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Vaccines, Synthetic / immunology
  • Yersinia pestis / immunology*

Substances

  • Antigens, Bacterial
  • LcrV protein, Yersinia
  • Plague Vaccine
  • Pore Forming Cytotoxic Proteins
  • Vaccines, Synthetic