Killed but metabolically active bacillus anthracis vaccines induce broad and protective immunity against anthrax

Justin Skoble, John W. Beaber, Gao Yi, Julie A. Lovchik, Laurie E. Sower, Weiqun Liu, William Luckett, Johnny Peterson, Richard Calendar, Daniel A. Portnoy, Rick C. Lyons, Thomas W. Dubensky

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Bacillus anthracis is the causative agent of anthrax. We have developed a novel whole-bacterial-cell anthrax vaccine utilizing B. anthracis that is killed but metabolically active (KBMA). Vaccine strains that are asporo- genic and nucleotide excision repair deficient were engineered by deleting the spoIIE and uvrAB genes, rendering B. anthracis extremely sensitive to photochemical inactivation with S-59 psoralen and UV light. We also introduced point mutations into the lef and cya genes, which allowed inactive but immunogenic toxins to be produced. Photochemically inactivated vaccine strains maintained a high degree of metabolic activity and secreted protective antigen (PA), lethal factor, and edema factor. KBMA B. anthracis vaccines were avirulent in mice and induced less injection site inflammation than recombinant PA adsorbed to aluminum hydroxide gel. KBMA B. anthracis-vaccinated animals produced antibodies against numerous anthrax antigens, including high levels of anti-PA and toxin-neutralizing antibodies. Vaccination with KBMA B. anthracis fully protected mice against challenge with lethal doses of toxinogenic unencapsulated Sterne 7702 spores and rabbits against challenge with lethal pneumonic doses of fully virulent Ames strain spores. Guinea pigs vaccinated with KBMA B. anthracis were partially protected against lethal Ames spore challenge, which was comparable to vaccination with the licensed vaccine anthrax vaccine adsorbed. These data demonstrate that KBMA anthrax vaccines are well tolerated and elicit potent protective immune responses. The use of KBMA vaccines may be broadly applicable to bacterial pathogens, especially those for which the correlates of protective immunity are unknown.

Original languageEnglish (US)
Pages (from-to)1649-1663
Number of pages15
JournalInfection and Immunity
Volume77
Issue number4
DOIs
StatePublished - Apr 2009

Fingerprint

Bacillus anthracis
Anthrax
Immunity
Vaccines
Anthrax Vaccines
Spores
Antigens
Vaccination
Ficusin
Aluminum Hydroxide
Inactivated Vaccines
Ultraviolet Rays
Neutralizing Antibodies
Point Mutation
DNA Repair
Genes
Guinea Pigs
Rabbits
Inflammation
Lung

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Skoble, J., Beaber, J. W., Yi, G., Lovchik, J. A., Sower, L. E., Liu, W., ... Dubensky, T. W. (2009). Killed but metabolically active bacillus anthracis vaccines induce broad and protective immunity against anthrax. Infection and Immunity, 77(4), 1649-1663. https://doi.org/10.1128/IAI.00530-08

Killed but metabolically active bacillus anthracis vaccines induce broad and protective immunity against anthrax. / Skoble, Justin; Beaber, John W.; Yi, Gao; Lovchik, Julie A.; Sower, Laurie E.; Liu, Weiqun; Luckett, William; Peterson, Johnny; Calendar, Richard; Portnoy, Daniel A.; Lyons, Rick C.; Dubensky, Thomas W.

In: Infection and Immunity, Vol. 77, No. 4, 04.2009, p. 1649-1663.

Research output: Contribution to journalArticle

Skoble, J, Beaber, JW, Yi, G, Lovchik, JA, Sower, LE, Liu, W, Luckett, W, Peterson, J, Calendar, R, Portnoy, DA, Lyons, RC & Dubensky, TW 2009, 'Killed but metabolically active bacillus anthracis vaccines induce broad and protective immunity against anthrax', Infection and Immunity, vol. 77, no. 4, pp. 1649-1663. https://doi.org/10.1128/IAI.00530-08
Skoble, Justin ; Beaber, John W. ; Yi, Gao ; Lovchik, Julie A. ; Sower, Laurie E. ; Liu, Weiqun ; Luckett, William ; Peterson, Johnny ; Calendar, Richard ; Portnoy, Daniel A. ; Lyons, Rick C. ; Dubensky, Thomas W. / Killed but metabolically active bacillus anthracis vaccines induce broad and protective immunity against anthrax. In: Infection and Immunity. 2009 ; Vol. 77, No. 4. pp. 1649-1663.
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