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 dosesparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 g 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.In the autumn of 2001, anthrax spores were intentionally released through the U.S. mail. This bioterror attack resulted in 11 cases of cutaneous anthrax and 11 cases of inhalational anthrax, 5 of which were fatal (7, 9). There has been an unprecedented level of public and private support for the development of new means of preventing and treating anthrax during the years following these attacks. Although antibiotics are nearly 100% effective in treating the cutaneous form of the disease, the case fatality rate for inhalational anthrax was estimated to be 75% or higher, even in the presence of supportive care and postexposure antibiotic treatment (information found at the CDC website [http://www.bt.cdc.gov/agent/anthrax /faq/signs.asp]). A recombinant form of the Bacillus anthracis protective antigen (rPA) is a candidate for replacement of Anthrax Vaccine Adsorbed (BioThrax), the currently licensed anthrax vaccine. Proposed applications of the rPA vaccine include prophylactic vaccination as well as therapeutic postexposure use in combination with antibiotics (5). Numerous preclinical studies have demonstrated that the rPA vaccine can provide complete protection against lethal inhalational anthrax (4, 8,11,13,14,18,23). Results of phase I clinical trials suggest that the vaccine is safe and immunogenic following intramuscular (i.m.) injection in humans (6).Most licensed and new vaccines under clinical development, including rPA, are administered by i.m. or subcutaneous injection using conventional needles and syringes. However, recent studies demonstrate that vaccine delivery to the skin can increase the magnitude of the immune response and, in some cases, do so using less vaccine than required with i.m. injection (1,2,10,12,(18)(19)(20)22). For example, clinical studies evaluating intradermal (i.d.) delivery of influenza vaccine have suggested that dose sparing relative to i.m. administration can be achieved (1, 10). Although conventional needles can be used...
