Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms.
A new anthrax vaccine under clinical investigation is based on recombinant Bacillus anthracis protective antigen (rPA). Here, we investigated microneedle-based cutaneous and nasal mucosal delivery of rPA in mice and rabbits. In mice, intradermal (id) delivery achieved up to 90% seroconversion after a single dose, compared with 20% after intramuscular (im) injection. Intranasal (inl) delivery of a liquid formulation required 3 doses to achieve responses that were comparable with those achieved via the id or im routes. In rabbits, id delivery provided complete protection against aerosol challenge with anthrax spores; in addition, novel powder formulations administered inl provided complete protection, whereas a liquid formulation provided only partial protection. These results demonstrate, for the first time, that cutaneous or nasal mucosal administration of rPA provides complete protection against inhalational anthrax in rabbits. The novel vaccine/device combinations described here have the potential to improve the efficacy of rPA and other biodefense vaccines.
Mikszta
John A
JA
BD Technologies, 21 Davis Dr., Research Triangle Park, NC 27709, USA. john_mikszta@bd.com
Sullivan
Vincent J
VJ
Dean
Cheryl
C
Waterston
Andrea M
AM
Alarcon
Jason B
JB
Dekker
John P
JP
Brittingham
John M
JM
Huang
Juan
J
Hwang
C Robin
CR
Ferriter
Matthew
M
Jiang
Ge
G
Mar
Kevin
K
Saikh
Kamal U
KU
Stiles
Bradley G
BG
Roy
Chad J
CJ
Ulrich
Robert G
RG
Harvey
Noel G
NG
D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D016503:Drug Delivery Systems; D051379:Mice; D011817:Rabbits; D014611:Vaccination
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial