Biological threat preparedness through vaccine development and stockpiling: challenges and strategic implications

Abstract

Biological threat agents such as Bacillus anthracis, Variola virus, and botulinum toxin pose serious risk to national security and public health due to their high transmissibility, lethality, and potential for weaponization. This study analyzes the current status of vaccine development and strategic stockpiling for five biological agents-B. anthracis, Variola virus, Yersinia pestis, Vibrio cholerae, and botulinum toxin-which are believed to be potentially weaponized by North Korea. It reviews both traditional and next-generation vaccine platforms, including live-attenuated, inactivated, protein subunit, viral vector, DNA, RNA, and novel technologies such as self-amplifying RNA vaccine and advanced adjuvants. The study also examines the vaccine stockpiling strategies of major countries and international organizations, with a focus on key pathogens, logistical frameworks, and policy implications. Based on the findings, the paper highlights the need for enhanced global cooperation, public-private partnerships, and long-term investment to improve vaccine preparedness. Developing rapid deployment systems under military coordination, along with harmonizing international vaccine-sharing protocols, is considered essential for strengthening biodefense and emergency response readiness.

Keywords: biodefense strategy; biological threats; public health preparedness; vaccine platform technologies; vaccine stockpiling; weaponizable biological agents.

Figure 1

Overview of vaccine platform technologies, including live-attenuated, inactivated (killed), protein subunit, viral vector, DNA, RNA, and virus-like particle (VLP) vaccines. Each platform differs in antigen delivery mechanism, immunogenicity, and applicability for rapid development and biodefense use. Created in BioRender. https://BioRender.com/14m8zdd.

Figure 2

Mechanism of anthrax toxin entry into host cells. The protective antigen (PA) binds to the anthrax receptor on the host cell membrane and is cleaved by furin protease into PA63. The cleaved PA oligomerizes, enabling binding of lethal factor (LF) and edema factor (EF). The toxin complex is internalized via endocytosis, and LF/EF are translocated into the cytosol, where they exert cytotoxic effects. Created in BioRender. https://BioRender.com/fu6awpz.

Figure 3

Mechanism of smallpox virus infecting host cells. The replication cycle of Vaccinia virus involves entry via fusion or endocytosis of the intracellular mature virus (IMV), followed by uncoating, DNA/RNA replication within viral factories, wrapping in the Golgi apparatus, and release as extracellular enveloped virus (EEV) through exocytosis. Created in BioRender. https://BioRen-der.com/s5e8sye.

Figure 4

Mechanism of Yersinia pestis infection and immune evasion. Following flea-borne transmission, Y. pestis invades macrophages using F1 pili and delivers effector proteins such as YopJ and YopE. YopJ inhibits TAK1 signaling, activating caspase-8 and inducing pyroptosis, while YopE facilitates inflammasome activation, promoting immune evasion. Created in BioRender. https://Bio-Render.com/4ohol2n.

Figure 5

Mechanism of cholera toxin activity in intestinal epithelial cells. The cholera toxin binds to ganglioside receptors via its B subunit and enters the host cell through endocytosis. The A1 fragment of the A subunit activates adenylate cyclase through G protein signaling, leading to an increase in intracellular cAMP levels. This cascade activates protein kinase A (PKA), triggering Cl⁻ and Na⁺ efflux and water secretion, ultimately resulting in severe diarrhea. Created in BioRender. https://BioRender.com/52xqq40.

Figure 6

Mechanism of action of botulinum neurotoxin. BoNT binds to its receptor at the neuromuscular junction, enters the presynaptic neuron, and cleaves SNARE proteins (including SNAP-25, syntaxin, and synaptobrevin). This cleavage prevents the release of acetylcholine, resulting in muscle paralysis. Created in BioRender. https://BioRender.com/si2qwsy.