TY - JOUR
T1 - A bivalent anthrax-plague vaccine that can protect against two Tier-1 bioterror pathogens, Bacillus anthracis and Yersinia pestis
AU - Tao, Pan
AU - Mahalingam, Marthandan
AU - Zhu, Jingen
AU - Moayeri, Mahtab
AU - Kirtley, Michelle L.
AU - Fitts, Eric C.
AU - Andersson, Jourdan A.
AU - Lawrence, William S.
AU - Leppla, Stephen H.
AU - Chopra, Ashok K.
AU - Rao, Venigalla B.
N1 - Publisher Copyright:
© 2017 Tao, Mahalingam, Zhu, Moayeri, Kirtley, Fitts, Andersson, Lawrence, Leppla, Chopra and Rao.
PY - 2017/6/26
Y1 - 2017/6/26
N2 - Bioterrorism remains as one of the biggest challenges to global security and public health. Since the deadly anthrax attacks of 2001 in the United States, Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the CDC as Tier-1 biothreat agents. Currently, there is no Food and Drug Administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vaccine. Here, we report the development of a single recombinant vaccine, a triple antigen consisting of all three target antigens, F1 and V from Y. pestis and PA from B. anthracis, in a structurally stable context. Properly folded and soluble, the triple antigen retained the functional and immunogenicity properties of all three antigens. Remarkably, two doses of this immunogen adjuvanted with Alhydrogel® elicited robust antibody responses in mice, rats, and rabbits and conferred complete protection against inhalational anthrax and pneumonic plague. No significant antigenic interference was observed. Furthermore, we report, for the first time, complete protection of animals against simultaneous challenge with Y. pestis and the lethal toxin of B. anthracis, demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized B. anthracis and/or Y. pestis. This bivalent anthrax-plague vaccine is, therefore, a strong candidate for stockpiling, after demonstration of its safety and immunogenicity in human clinical trials, as part of national preparedness against two of the deadliest bioterror threats.
AB - Bioterrorism remains as one of the biggest challenges to global security and public health. Since the deadly anthrax attacks of 2001 in the United States, Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, gained notoriety and were listed by the CDC as Tier-1 biothreat agents. Currently, there is no Food and Drug Administration-approved vaccine against either of these threats for mass vaccination to protect general public, let alone a bivalent vaccine. Here, we report the development of a single recombinant vaccine, a triple antigen consisting of all three target antigens, F1 and V from Y. pestis and PA from B. anthracis, in a structurally stable context. Properly folded and soluble, the triple antigen retained the functional and immunogenicity properties of all three antigens. Remarkably, two doses of this immunogen adjuvanted with Alhydrogel® elicited robust antibody responses in mice, rats, and rabbits and conferred complete protection against inhalational anthrax and pneumonic plague. No significant antigenic interference was observed. Furthermore, we report, for the first time, complete protection of animals against simultaneous challenge with Y. pestis and the lethal toxin of B. anthracis, demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized B. anthracis and/or Y. pestis. This bivalent anthrax-plague vaccine is, therefore, a strong candidate for stockpiling, after demonstration of its safety and immunogenicity in human clinical trials, as part of national preparedness against two of the deadliest bioterror threats.
KW - Anthrax vaccines
KW - Biodefense vaccines
KW - Bivalent vaccines
KW - Capsular antigen f1
KW - Low calcium response V antigen LcrV
KW - Plague vaccine
KW - Protective antigen
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UR - http://www.scopus.com/inward/citedby.url?scp=85021232064&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.00687
DO - 10.3389/fimmu.2017.00687
M3 - Article
C2 - 28694806
AN - SCOPUS:85021232064
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JUN
M1 - 687
ER -