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.
Subject(s)
Anthrax Vaccines/administration & dosage , Anthrax Vaccines/immunology , Anthrax/prevention & control , Antigens, Bacterial/administration & dosage , Antigens, Bacterial/immunology , Bacterial Toxins/administration & dosage , Bacterial Toxins/immunology , Administration, Cutaneous , Animals , Female , Immunoglobulin G/blood , Injections, Intramuscular , Microinjections , Needles , Rabbits , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology , Vaccines, SyntheticABSTRACT
Flaviviral diseases such as yellow fever, Japanese encephalitis (JE) and dengue hemorrhagic fever cause enormous morbidity and mortality worldwide. There is an urgent need for alternative technologies for mass vaccination against these and other diseases, particularly in the developing world. Here, we administered a live attenuated, chimeric JE vaccine (ChimeriVax)-JE) to nonhuman primates by skin microabrasion and intradermal delivery using microneedles. Both cutaneous delivery methods induced mild viremia similar in magnitude to that observed following subcutaneous (SC) injection. The duration of viremia induced by cutaneous delivery (5-7 days), however, was substantially longer than via SC (0-3 days). In addition, mean neutralizing antibody titers in cutaneous delivery groups were up to 7-fold greater than via SC injection. There were no safety issues identified and both cutaneous delivery methods appeared to be well tolerated. Thus, cutaneous delivery may represent a minimally-invasive alternative approach for flavivirus vaccines that more closely resembles the natural route of viral infection.
