Faculty Collaboration Database

Flagellin-F1-V fusion protein is an effective plague vaccine in mice and two species of nonhuman primates. Clin Vaccine Immunol 2009 Jan;16(1):21-8

Date

11/07/2008

Pubmed ID

18987167

Pubmed Central ID

PMC2620661

DOI

10.1128/CVI.00333-08

Scopus ID

2-s2.0-58149392737 (requires institutional sign-in at Scopus site)   113 Citations

Abstract

A number of studies have clearly demonstrated that flagellin is a potent adjuvant that promotes robust immune responses when it is given with a protein antigen. In view of the potential biological and practical benefits of a recombinant protein vaccine composed of a single fusion protein containing flagellin and antigen, we have evaluated the efficacy of a fusion protein composed of flagellin and two protective antigens of Yersinia pestis (F1 and V) in eliciting protection against respiratory challenge with Y. pestis. Flagellin-F1-V was produced and purified in high yield under good manufacturing practices conditions. The fusion protein retains full Toll-like receptor 5-stimulating activity in vitro. Using a prime-boost immunization protocol, we found that flagellin-F1-V elicits robust antigen-specific humoral immunity in mice and two species of nonhuman primates. Immune mice were fully protected against intranasal challenge with 150 mean tolerated doses of Y. pestis CO92. In immune mice, the bacteria were completely cleared within 3 days after challenge. Flagellin-F1-V exhibited full stability for at least 297 days at 4 degrees C and at least 168 days at 25 degrees C. At between 29 and 84 days at 37 degrees C, the protein exhibited a loss of biological activity that appeared to be associated with a substantial change in protein diameter, possibly due to oligomerization. On the basis of our results, we believe that flagellin-F1-V is an outstanding candidate for evaluation in studies with humans.

Author List

Mizel SB, Graff AH, Sriranganathan N, Ervin S, Lees CJ, Lively MO, Hantgan RR, Thomas MJ, Wood J, Bell B

Author

Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Bacterial
Antigens, Bacterial
Bacterial Proteins
Drug Stability
Drug Storage
Female
Flagellin
Immunization, Secondary
Macaca fascicularis
Male
Mice
Mice, Inbred BALB C
Plague Vaccine
Pore Forming Cytotoxic Proteins
Recombinant Fusion Proteins
Survival Analysis
Temperature
Time Factors
Toll-Like Receptor 5
Virulence Factors
Yersinia pestis