Marrack and Kappler, 1994; Medzhitov and Janeway, 1997; Okada et al., 1997; Cohen et al., 1998; Kim et al., 1997, 1998). Subsequently, an “adaptive” or antigen-1998; Krieg et al., 1998b; Weiss et al., 1998). specific immune response is generated against determi-The use of DNA plasmids offers several important nants expressed uniquely by the pathogen. Efforts are advantages over conventional vaccine strategies for deunderway to use DNA-based technology, including DNA veloping antibiowarfare agents. DNA vaccines can be vaccines and immunostimulatory synthetic oligodeoxyprepared from minute amounts of DNA isolated from a nucleotides (ODN), to induce both innate and adaptive pathogen, eliminating the need to culture or attenuate immune responses against biothreat agents. large stocks of deadly bacteria or viruses. For this purpose, the genes that encode immunogenic proteins can DNA Vaccines to Counter Bioterrorism be rapidly cloned into pretested vectors and used for The ability of antigen-encoding DNA plasmids to induce vaccine production. Even if the immunogenic genes/cellular and humoral immune responses against patho- proteins from a given pathogen are unknown, the entire genic viruses, bacteria, and toxins is revolutionizing vac- genome can be “shotgun” cloned into such vectors and cine development (Figure 1). DNA vaccines are com- then screened for activity (Johnston and Barry, 1997). posed of an antigen-encoding gene whose expression Using these approaches, scientists have developed is regulated by a strong mammalian promoter expressed first-generation DNA vaccines against biothreat agents. on a plasmid backbone of bacterial DNA (Ulmer et al., These include vaccines targeting cell surface, envelope, and/or nucleoproteins expressed by bacterial and viral pathogens (such as Ebola and Yersinia [Vanderzanden* To whom correspondence should be addressed (e-mail: klinman@