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. 2006 Dec;74(12):6806-10.
doi: 10.1128/IAI.01210-06. Epub 2006 Oct 9.

Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine

Affiliations

Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine

John A Mikszta et al. Infect Immun. 2006 Dec.

Abstract

The recombinant protective antigen (rPA) of Bacillus anthracis is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. Intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following primary and booster inoculation. This dose-sparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 mug of rPA displayed 100% protection from aerosol spore challenge, while i.m. injection of the same dose provided slightly lower protection (71%). Groups immunized with lower antigen doses were partially protected (13 to 29%) regardless of the mode of administration. Overall, our results suggest rPA formulated with aluminum adjuvant and administered to the skin by a microneedle-based device is as efficacious as i.m. vaccination.

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Figures

FIG. 1.
FIG. 1.
PA-specific serum IgG levels following immunization with anthrax rPA vaccine. Rabbits (eight per group) were immunized on d0 and d28. Displayed are antibody response levels from rabbits at d14 (A), d28 (B), d42 (C), and d56 (D). Data represent mean PA-specific IgG levels ± standard errors of the mean.
FIG. 2.
FIG. 2.
Relationship between antibody response levels and survival following aerosol challenge with 263 ± 97 LD50 of Ames strain anthrax spores. (A) Survival versus time. Rabbits were challenged at approximately d80 and monitored daily for morbidity and mortality. Eight animals were challenged per group except for the following groups: i.d., 10 μg (six animals); i.m., 10 μg (seven animals); i.m., 0.08 μg (seven animals); and unimmunized (six animals). In these groups, fatalities had occurred before challenge. These fatalities did not appear to be due to the vaccine or the method of delivery, since they occurred in unimmunized control rabbits as well as in animals immunized by the i.d. and i.m. routes. (B) TNA titers at d56 for individual rabbits that survived or died. (C) Anti-PA IgG levels at d56 for individual rabbits that survived or died.

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