Anthrax Vaccine Antigen-Adjuvant Formulations Completely Protect New Zealand White Rabbits against Challenge with Bacillus anthracis Ames Strain Spores |
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Authors: | Kristina K. Peachman Qin Li Gary R. Matyas Sathish B. Shivachandra Julie Lovchik Rick C. Lyons Carl R. Alving Venigalla B. Rao Mangala Rao |
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Affiliation: | aU.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, USA;bDepartment of Biology, The Catholic University of America, Washington, DC, USA;cDivision of Retrovirology, Walter Reed Army Institute of Research, U. S. Military HIV Research Program, Rockville, Maryland, USA;dUniversity of New Mexico, Health Sciences Center, Albuquerque, New Mexico, USA |
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Abstract: | In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development. |
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