Rabies virus glycoprotein as a carrier for anthrax protective antigen.
Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems.
Smith
Mary Ellen
ME
Department of Microbiology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Koser
Martin
M
Xiao
Sa
S
Siler
Catherine
C
McGettigan
James P
JP
Calkins
Catherine
C
Pomerantz
Roger J
RJ
Dietzschold
Bernhard
B
Schnell
Matthias J
MJ
D000818:Animals; D000881:Anthrax / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics* / Q000276:immunology; D023482:Bioterrorism / Q000517:prevention & control; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D011819:Rabies Vaccines / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001427:Bacterial Toxins; D006023:Glycoproteins; D011819:Rabies Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C030325:anthrax toxin; C064951:glycoprotein G, Rabies virus