Open AccessKilled but Metabolically Active Bacillus anthracis Vaccines Induce Broad and Protective Immunity against Anthrax
Author(s) -
Justin Skoble,
John W. Beaber,
Yi Qin Gao,
Julie Lovchik,
Laurie Sower,
Weiqun Liu,
William Luckett,
Johnny W. Peterson,
Richard Calendar,
Daniel A. Portnoy,
C. Rick Lyons,
Thomas W. Dubensky
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00530-08
Subject(s) - bacillus anthracis , anthrax vaccines , anthrax toxin , microbiology and biotechnology , biology , virology , vaccination , immunity , attenuated vaccine , virulence , antibody , immune system , immunization , immunology , recombinant dna , bacteria , gene , fusion protein , dna vaccination , biochemistry , genetics
Bacillus anthracis is the causative agent of anthrax. We have developed a novel whole-bacterial-cell anthrax vaccine utilizingB. anthracis that is killed but metabolically active (KBMA). Vaccine strains that are asporogenic and nucleotide excision repair deficient were engineered by deleting thespoIIE anduvrAB genes, renderingB. anthracis extremely sensitive to photochemical inactivation with S-59 psoralen and UV light. We also introduced point mutations into thelef andcya 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. KBMAB. anthracis vaccines were avirulent in mice and induced less injection site inflammation than recombinant PA adsorbed to aluminum hydroxide gel. KBMAB. anthracis -vaccinated animals produced antibodies against numerous anthrax antigens, including high levels of anti-PA and toxin-neutralizing antibodies. Vaccination with KBMAB. 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 KBMAB. 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.