Smallpox, eradicated globally in 1980, remains a major biodefense concern due to retained Variola virus stocks and the absence of population immunity following cessation of routine vaccination. Monkeypox virus (MPXV), a related orthopoxvirus, has reemerged as a global public health threat, with major outbreaks in 2022 and renewed spread from 2024 onward.

Ricin, a potent protein toxin derived from Ricinus communis, is considered one of the most significant threats in cases of bioterrorism, homicide, suicide, and accidental acute poisoning. However, its clinical and pathological features in fatal cases have not been systematically summarized. This systematic review aimed to summarize the current evidence regarding the clinical manifestations, toxicological biomarkers, autopsy findings, and medico-legal aspects of fatal ricin poisoning. A comprehensive literature search was conducted in accordance with PRISMA guidelines. Original studies, case reports, and case series reporting detailed clinical, toxicological, or autopsy data following fatal or near-fatal human exposure to ricin were included in the review. The available evidence suggests a relatively consistent clinical course, characterized by rapid progression from mild, nonspecific gastrointestinal symptoms to hypovolemic shock, multi-organ failure, and refractory cardiovascular collapse. Ricinine was consistently detected in blood, urine, and postmortem tissues, supporting its role as a reliable biomarker of ricin exposure, although current evidence is insufficient to establish definitive correlations with poisoning severity or toxicokinetics. Reported autopsy findings commonly included hemolysis, hemorrhagic necrosis of the gastrointestinal tract, hepatic injury, renal tubular necrosis, and evidence supporting the presence of a capillary leak syndrome. Several specific medico-legal challenges emerged from the reviewed literature, including the need for the development of novel analytical methods with improved detection limits and quantification capabilities for ricinine, the interpretation of postmortem redistribution phenomena, the distinction between lethal and non-lethal exposures, and the differential diagnosis with other septic shock-like syndromes. Overall, the available evidence suggests a relatively consistent clinicopathological pattern associated with fatal ricin poisoning that can be corroborated through ricinine detection, while emphasizing the importance of early toxicological investigations, particularly when no history of exposure is available. These findings provide a concise and integrated body of evidence to support clinical management, inform forensic investigations, and enhance public health preparedness, while highlighting the need for standardized postmortem sampling protocols and further research into the toxicodynamics of ricin in humans.

The plant toxin ricin, derived from the castor bean plant Ricinus communis, is a major bioterrorism agent that requires analytical strategies to confirm both toxin identity and functionality. Ricin consists of an enzymatically active A chain (RTA) and a galactose-binding B chain (RTB) linked by an inter-chain disulfide bond. Conventional bottom-up mass spectrometry identifies ricin using proteotypic peptides from the individual chains but does not establish whether the toxin is present as an intact, active holotoxin. Here, we present an integrated workflow that enables structural and functional detection of ricin present at trace levels in complex matrices. The proteomic mass spectrometry assay combines targeted detection of multiple peptides from both chains with the challenging inter-chain disulfide-linked peptide, an unambiguous marker of intact ricin. Dramatic enhancement of sensitivity in complex matrices was achieved through optimized immunocapture with sheep anti-mouse magnetic beads, enabling ∼80% recovery of ricin and compatibility with nano-LC-MS/MS acquisition at concentrations below 1 ng/mL. The proteomic method matched the sensitivity of the parallel adenine-release assay, with limits of detection (LOD) down to 10 pg/mL for the A-, B-chain peptides and adenine. The most abundant linker peptide variants were detected at 500 pg/mL. Good repeatability was achieved, with average CV values below 20% across analyses and matrices. This approach enables simultaneous assessment of chain connectivity and biological activity, increasing confidence in identification relative to conventional approaches and providing unique insights into the toxin's functionality.

The ProVector® Biodegradable, visual Olfactory, and Chemical (BVOC™) vector control device was tested to attract and control mosquitoes, meet Department of Defense (DoD) thermal and camouflage criteria, and applicability for deployment by air and hand. The BVOC device is composed of non-toxic biodegradable composite materials that can be formed into various containers and sizes. The BVOC, with pesticides can be deployed from the air, by air gun, and by hand. It can be camouflaged to match the military operational environment and incorporate low thermal detectability, and incorporates biodegradable, visual, olfactory, and chemical components to attract and control mosquito populations and potentially other vectors. The BVOC offers several advantages over current technologies; 1) reduces the impact on the environment, 2) targets adult and larvae mosquitoes with less pesticide,as it is retained in a bait station and reduces impact on non-target organisms, 3) can be used for collection of mosquito species, and 4) reduces risk to military personnel by blending into the environment (visual and IR) and eliminates the need to refill or collect the device. The device is designed for the safety of military personnel and requires no specialized training. The BVOC can be used for control and surveillance of mosquitoes and other vectors from tree level to ground level, and water. The ProVector BVOC device can also be used to release the MEVLABS Multi-Bioagent Simulant and MEVLABS Infectious disease control reagents, and has both military and civilian applications.

Several ixodid tick species that are competent vectors of disease-causing pathogens to humans, domestic animals and wildlife are expanding their geographic range, with population redistribution within their respective geographic range. These range and population distribution changes pose a significant threat to U.S. Military Health Service beneficiaries, working dogs, and the public health at large. We report new findings of established Gulf Coast tick (Amblyomma maculatum Koch) populations occurring outside the historic and most recently described geographic range projections for the species. More than 470 ixodid tick specimens collected from farm dogs were identified and tested for rickettsial pathogens during 2023 and 2024. Of the ticks submitted and identified to species, 14% were confirmed to be Gulf Coast ticks detected. Of the Gulf Coast ticks, 6.82% were positive for Borrelia spp., one tick was positive for Ehrilichia spp., and 93.18% were positive for Rickettsia spp. As the geographic range of established Gulf Coast tick and other ixodid tick vector populations continues to expand northerly and westerly into the Southcentral and southern Midwest Regions of the United States, the increasing threat to human and veterinary health will be an increasingly significant concern.

Correlates that predict protection against intracellular pathogens, including the highly pathogenic bacterium Francisella, are of interest to evaluate novel candidate vaccines and to facilitate clinical trials. We have previously established an in vitro co-culture assay that measures the control of intramacrophage bacterial replication by immune T cells and serves as a functional correlate. Moreover, this assay is a tool to identify additional molecular correlates of protection and to better understand protective T cell responses against Francisella. To study the role of metabolic shifts in protective T cell responses, we used co-cultures to profile the metabolic activities of macrophages and lymphocytes from mice vaccinated with F. tularensis Live Vaccine Strain (LVS). Previous studies indicated that LVS infection of macrophages dysregulates macrophage metabolism and limits glycolysis. Here, we show that co-cultures of LVS-infected macrophages with LVS-primed lymphocytes, which controlled intramacrophage bacterial growth, exhibited more glycolysis than co-cultures containing naïve cells. Further, LVS-primed lymphocytes exhibited a significant loss of respiratory capacity over time, consistent with a transition to an effector T cell state. Gene expression analyses of splenic T cells recovered from co-cultures revealed a set of metabolic genes that were not only upregulated in glycolytic LVS-primed T cells but could also be detected in total primed splenocytes and peripheral blood lymphocytes. Taken together, we find that LVS-primed effector T cells override bacterial-induced metabolic dysregulation in macrophages to control bacterial infection. These results support future studies exploring the use of metabolic intermediates as potential correlates of protection.IMPORTANCECurrently, there are no licensed vaccines against the deadly bacterium Francisella tularensis, which causes the disease called tularemia in people and in many animals. F. tularensis is also a potential bioterrorism agent. In this study, we showed that metabolic activity measurements of cells from mice immunized with a candidate tularemia vaccine correlated well with protection against disease. These results suggest a new approach to developing lab tests that can predict successful vaccination before undertaking a clinical trial.

Melioidosis, caused by the gram-negative bacillus Burkholderia pseudomallei - a Tier 1 Select Biological agent - remains a significant cause of severe community-acquired infection in tropical regions, but with recent expanding recognition in temperate climates, including the United States. Pulmonary involvement is the most frequent clinical manifestation, ranging from subclinical nodules to fulminant necrotizing pneumonia and acute respiratory distress syndrome. Despite its clinical severity, melioidosis remains underdiagnosed due to its radiologic mimicry of tuberculosis, broad clinical manifestations, and limited laboratory capacity in many endemic areas. Special Operations Forces (SOF) participating in field exercises or operations in B. pseudomallei endemic countries are at significantly increased risk of infection. Accordingly, SOF medical providers should maintain a high index of suspicion for melioidosis and be familiar with its clinical recognition, diagnosis, and management.

Bioterrorism involves the intentional release of biological agents capable of causing mass casualties, public health emergencies, and societal disruption. As frontline healthcare providers, nurses play a critical role in early detection, isolation, emergency care, and surveillance. However, substantial gaps exist in nursing bioterrorism preparedness across healthcare settings, and implementation determinants influencing preparedness remain insufficiently synthesised.

Ribosome-inactivating proteins are a class of toxins that target eukaryotic ribosomes, inhibit protein synthesis, and ultimately induce cell death. Several of these toxins pose significant clinical and public health threats. Among these, ricin, derived from the castor bean plant (Ricinus communis), is a highly potent biotoxin with recognized bioterrorism potential. Other ribosome-inactivating proteins, including Shiga toxin produced by pathogenic Shigella and Escherichia coli, as well as mucoricin from Mucorales fungi, contribute to disease severity and can lead to life-threatening complications. Despite these risks, no approved therapeutics are currently available. The development of effective inhibitors depends on robust and well-defined strategies to identify and validate small molecules that disrupt toxin-ribosome interactions. Efforts to target the catalytic active site have met with limited success, largely due to its broad, shallow, and highly polar architecture, which is not conducive to high-affinity binding by drug-like molecules. In contrast, the ribosome-binding interface represents a more tractable target, as it is essential for toxin recruitment and offers more structurally defined and druggable features. Inhibitors targeting this interface can also exert allosteric effects by disrupting long-range conformational coupling between the ribosome-binding region and the active site, thereby attenuating catalytic activity without directly engaging the catalytic pocket. In this review, we compile and evaluate biophysical and biochemical assays for the discovery and characterization of small-molecule inhibitors that target toxin-ribosome interactions. We examine in vitro binding approaches, including surface plasmon resonance-based fragment screening and fluorescence anisotropy assays for ranking inhibitory activity. We further review biochemical and molecular assays that assess ribosome protection from toxin-mediated depurination, along with complementary cell-based assays that evaluate functional rescue in cellular systems. Collectively, this review consolidates current screening methodologies and highlights opportunities to refine assay strategies, thereby supporting the advancement of targeted therapeutics.

Technology has offered considerable means to create, enhance, and upkeep biosecurity during the last quarter-century. Mostly this refers to routine health promotion means, more or less modified for the much more complex environment of Biosecurity, which includes perpetrated biothreats and thus involves hostile intelligence set to nullify response. This narrative review describes the complexity of the field and presents to bioscience-cognitive audience an update of the current state-of-the-art approaches, their usefulness in Biosecurity applications and their suitability for the diverse current format. The research involved plain internet (Google) search engine and Pubmed searches with matching terms from May 2025 to January 2026. Regarding diagnostics, the Molecular Diagnostics applicable in Resource-Limited Settings, the serodiagnostics, now available in solid formats as Rapid Diagnostic Tests, improved and more powerful Microscopy and cultures updated to Culturomics are the focus. Support functions, from bioinformatics to remote and cybernetic applications, such as lab and diagnostic automations, increase responsiveness and flexibility. Intervention, the second major arm of Biosecurity is also evolving despite the scarcity of new antibiotics. Different classes of Bioamenities combined with advanced and controllable delivery methods emerge for routine medicine and may be adopted, adapted, and modified for Biosecurity use.

Biosecurity threats are issues of public health importance because of their implications for global health security. Although some strategies have been implemented by global organizations to mitigate risks from natural, accidental, or deliberate biological threats, empirical data on global health preparedness for biosecurity threats generally are still evolving. Hence, this study aimed to synthesize existing evidence of the role of emerging technologies in enhancing global health preparedness for biosecurity threats. Using a PRISMA-guided protocol, we conducted a systematic review of (peer-reviewed) published and grey articles regarding biosecurity preparedness and emerging technologies in PubMed, Google Scholar, and EBSCOHOST from 2015 to 2026. Extracted data were used for narrative synthesis. Most relevant and representative 51 out of a total of 349 identified papers were selected and reviewed for this study. Key technologies identified include artificial intelligence, genomic surveillance, synthetic biology, biosensors, robotics, and digital health platforms. These technologies improve outbreak detection, surveillance, and response coordination. However, challenges include dual-use risks, ethical concerns, inequitable access, and regulatory gaps. We conclude that emerging technologies offer great prospects for enhancing global health preparedness but require robust governance frameworks, equitable access, and interdisciplinary collaboration to mitigate risks and maximize benefits. A multidisciplinary approach involving synergy between relevant stakeholders is required to combat biosecurity threats, as the world has become a global village through advances in technology.

Cross-border biological threats are increasing both in frequency and complexity. Whether of natural, accidental, or deliberate origin, they pose serious risks for public and animal health, economics, and national security. They can also create vulnerabilities capable of being exploited by malicious actors, worsening health crises, and undermining trust in response efforts. Although both the health and security sectors share a common interest in mitigating these threats, they often operate in silos. The One Health approach, which aims at optimizing the health of animals, people, and the environment, has gained momentum in recent years; however, its implementation faces challenges such as weak governance, lack of resources, and, notably, the exclusion of security actors whose roles and capacities remain underrecognized. Security actors play a vital role in preventing, detecting, and investigating criminal activities related to biological incidents as well as supporting health actors with biological threat response. There is a general lack of understanding of the One Health approach within the security community and health is often predominately viewed through a human safety viewpoint often omitting animal and environmental health. This commentary advocates for the mutual integration of One Health and security approaches to strengthen resilience against cross-border biological threats. Concrete examples and recommendations to foster integration are discussed such as updating legislation, formalizing information sharing mechanisms, and undertaking joint capacity building, all while recognizing common challenges in mutual integration. To protect people, animals, and the environment alike, it is time to act to ensure coordinated efforts to mitigate cross-border biological threats.

Natural toxins represent structurally diverse class of bioactive compounds that pose underrecognized risks extending beyond traditional food safety concerns into chemical security applications. Recent high-profile incidents have highlighted critical gaps in detection capabilities, clinical management, and regulatory frameworks governing these substances. This review discusses the diversity, potency profiles and security implications of natural toxins with a focus on compounds with outstanding acute toxicity, such as batrachotoxin from Phyllobates poison dart frogs (LD50 2-3 μg/kg intravenously), amatoxins from Amanita species (LD50 100-300 μg/kg) and conotoxins from cone snails (LD50 10-100 μg/kg), comparable to synthetic chemical warfare agents. Critical vulnerabilities include the absence of specific antidotes, analytical challenges related to structural diversity and incomplete coverage by routine toxicological screens. Historical examples of intentional intoxications (e.g., ricin assassination of Georgi Markov in 1978 and bioterrorism by mail between 2003 and 2013) illustrate the general availability but also the limitations of this modus operandi. Developments in high-resolution mass spectrometry and computational toxicology offer promising improvements in detection. International regulations under the Chemical Weapons Convention need further improvement to address the growing threat posed by these natural but potentially weaponizable compounds.

Abrin is a type II ribosome-inactivating protein extracted from the seeds of Abrus precatorius. Due to its extreme toxicity and ease of acquisition, it is classified as a Category B bioterrorism agent, and no effective antidote is currently available. In this study, a fully human antibody against abrin, designated A140, was generated via screening of a fully human phage-display antibody library and subsequent expression. The A140 antibody demonstrates high affinity while maintaining specificity for its target antigen. It exhibited potent neutralizing efficacy against abrin toxin in both in vitro and in vivo assays. Intriguingly, the A140 antibody, which enters cells via clathrin-dependent and macropinocytic pathways and is subsequently trafficked to lysosomes, does not prevent the cellular entry of abrin, suggesting that its intracellular neutralization activity may function within the lysosomal compartment. Molecular docking studies based on AlphaFold 3 (AF3) indicate that A140 primarily recognizes residues Ser14, Arg169, and Asn173 of the alpha chain of abrin-a. Transcriptomic analysis based on Vero E6 cells showed that A140 antibody treatment was able to reverse almost 80% of the transcriptomic changes induced by abrin. Preliminary toxicity analysis shows that a high dose of the A140 antibody has no impact on the heart, liver, spleen, lungs, kidneys, and other major organs in mice. Our findings indicate that the A140 antibody, as a novel fully human antibody, holds promise as a key therapeutic agent for the treatment of abrin intoxication.