%0 Journal Article
%T Advanced Development of the rF1V and rBV A/B Vaccines: Progress and Challenges
%A Mary Kate Hart
%A George A. Saviolakis
%A Susan L. Welkos
%A Robert V. House
%J Advances in Preventive Medicine
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/731604
%X The development of vaccines for microorganisms and bacterial toxins with the potential to be used as biowarfare and bioterrorism agents is an important component of the US biodefense program. DVC is developing two vaccines, one against inhalational exposure to botulinum neurotoxins A1 and B1 and a second for Yersinia pestis, with the ultimate goal of licensure by the FDA under the Animal Rule. Progress has been made in all technical areas, including manufacturing, nonclinical, and clinical development and testing of the vaccines, and in assay development. The current status of development of these vaccines, and remaining challenges are described in this chapter. 1. Introduction Certain highly pathogenic microorganisms and their products have the potential to be used as weapons against either military or civilian populations. The Centers for Disease Control and Prevention (CDC) classifies these agents into one of three categories (A, B, or C) according to seriousness of consequences following exposure (http://emergency.cdc.gov/agent/agentlist-category.asp; accessed April 7, 2011). The US Department of Defense (DoD) has a long history of developing therapeutics and prophylactics (vaccines) to protect the warfighter against offensive use of these agents. Until relatively recently, these countermeasures could be used under an investigational new drug application (IND) mechanism. Now, the DoD mandates that any such products administered to the US warfighters be licensed by the US Food and Drug Administration (FDA). Currently, DVC is developing two vaccines for DoD¡¯s Joint Vaccine Acquisition Program (JVAP); these include a recombinant vaccine to protect against fatal botulism following inhalational exposure to the A1 and B1 serotypes of botulinum neurotoxin (rBV A/B), as well as a recombinant vaccine to protect against pneumonic plague following inhalational exposure to Yersinia pestis (Y. pestis) (rF1V). The specific performance and regulatory requirements, progress, challenges, and successes in each program are reviewed below. 2. Disease Characteristics 2.1. Botulism Botulism is caused by neurotoxins produced by the bacterium Clostridium botulinum (C. botulinum), and disease presents in different forms including infant, wound, adult colonization, and foodborne botulism [1]. The clinical picture is due to cholinergic inhibition, and characteristic signs include a descending muscle weakness, dry mouth, difficulty swallowing, slurred speech, double or blurred vision, and drooping eyelids. The botulinum neurotoxin (BoNT) eventually causes paralysis of the
%U http://www.hindawi.com/journals/apm/2012/731604/