Induction of protective immunity against lethal anthrax challenge with a patch.
BACKGROUND
Transcutaneous immunization (TCI) is a needle-free technique that delivers antigens and adjuvants to potent epidermal immune cells. To address critical unmet needs in biodefense against anthrax, we have designed a novel vaccine delivery system using a dry adhesive patch that simplifies administration and improves tolerability of a subunit anthrax vaccine.


METHODS
Mice and rabbits were vaccinated with recombinant protective antigen of Bacillus anthracis and the heat-labile toxin of Escherichia coli. Serologic changes, levels of toxin-neutralizing antibodies (TNAs), and pulmonary and nodal responses were monitored in the mice. A lethal aerosolized B. anthracis challenge model was used in A/J mice, to demonstrate efficacy.


RESULTS
The level of systemic immunity and protection induced by TCI was comparable to that induced by intramuscular vaccination, and peak immunity could be achieved with only 2 doses. The addition of adjuvant in the patch induced superior TNA levels, compared with injected vaccination.


CONCLUSIONS
Anthrax vaccine patches stimulated robust and functional immune responses that protected against lethal challenge. Demonstration of responses in the lung suggests that a mechanism exists for protection against challenge with aerosolized anthrax spores. A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.
IOMAI, Gaithersburg, Maryland 20878, USA. rkenney@iomai.com
Richard T
RT
Kenney
Jianmei
J
Yu
Mimi
M
Guebre-Xabier
Sarah A
SA
Frech
Adam
A
Lambert
Barbara A
BA
Heller
Larry R
LR
Ellingsworth
James E
JE
Eyles
E Diane
ED
Williamson
Gregory M
GM
Glenn
D000276:Adjuvants, Immunologic; D000279:Administration, Cutaneous; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D029968:Escherichia coli Proteins; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; C027538:heat-labile enterotoxin, E coli