High Containment Facilities Research Articles

The planetary protection strategy of Mars Sample Return’s Earth Return Orbiter mission

The Mars Sample Return campaign aims to use three flight missions and one ground element to safely bring rock cores, regolith and atmospheric samples from the surface of Mars to Earth to answer key questions about the geologic and climate history of Mars, including the potential for ancient life. Since its landing in Jezero Crater in 2021, the first mission, NASA’s Mars 2020, has collected a number of samples on the crater floor and on the delta using the Perseverance rover. Subsequent missions would recover the sealed sample tubes, launch them into Mars orbit, and transport them back to Earth. The ground element would be a high-containment facility that would isolate and protect the samples during initial sample characterization, which would include sample safety assessments and time-sensitive scientific investigations. These elements are currently in the planning and design stages of development, and represent an international effort of NASA, the European Space Agency (ESA), and many industry partners. The work presented here provides an overview of the planetary protection strategy of the third flight mission, the ESA-led Earth Return Orbiter, which hosts the NASA-provided Capture, Containment, and Return System. The orbiter would detect and capture the container with up to 30 sealed tubes previously put in Martian orbit, contain them in redundant containers to ensure that no potentially hazardous Mars particles are released, and return them to Earth through an entry vehicle. Both NASA and ESA policies comply with the United Nations’ Outer Space Treaty by planning to protect Earth’s biosphere from any potential adverse effects from material returned from solar system bodies beyond the Earth-Moon system. In the conduct of Mars Sample Return, the two agencies have mutually agreed to apply approaches consistent with their own planetary protection standards to the campaign elements they each provide.

Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein

Louping ill virus (LIV) is a tick-borne flavivirus that predominantly causes disease in livestock, especially sheep in the British Isles. A preventive vaccine, previously approved for veterinary use but now discontinued, was based on an inactivated whole virion that likely provided protection by induction of neutralizing antibodies recognizing the viral envelope (E) protein. A major disadvantage of the inactivated vaccine was the need for high containment facilities for the propagation of infectious virus, as mandated by the hazard group 3 status of the virus. This study aimed to develop high-efficacy non-infectious protein-based vaccine candidates. Specifically, soluble envelope protein (sE), and virus-like particles (VLPs), comprised of the precursor of membrane and envelope proteins, were generated, characterized, and studied for their immunogenicity in mice. Results showed that the VLPs induced more potent virus neutralizing response compared to sE, even though the total anti-envelope IgG content induced by the two antigens was similar. Depletion of anti-monomeric E protein antibodies from mouse immune sera suggested that the neutralizing antibodies elicited by the VLPs targeted epitopes spanning the highly organized structure of multimer of the E protein, whereas the antibody response induced by sE focused on E monomers. Thus, our results indicate that VLPs represent a promising LIV vaccine candidate.

Evaluation of an iELISA for detection and quantification of rabies antibodies in domestic dog sera

Many rabies endemic-countries have recognized rabies as a public health problem that can be eliminated. As a result, some countries have started implementing small-scale vaccination programs with the aim of scaling them up. Post-vaccination serological monitoring is crucial to assess the efficacy of these programs. The recommended serological tests, the rapid fluorescent focus inhibition test, and the fluorescent antibody virus neutralization (FAVN) are accurate; however, the procedures require considerable expertise and must be carried out in high containment facilities, which are often not available in rabies endemic countries. Given these constraints, enzyme linked immunosorbent assays (ELISAs) have been considered as alternative methods to neutralization tests. This is the first study to evaluate, under field conditions, the performance of the commercial rabies indirect-ELISA (iELISA), the PlateliaTM Rabies II kit ad usum Veterinarium kit, using sera from domestic dogs. Serum samples were collected from two groups of community dogs in northern Tanzania: i) dogs with no history of vaccination against rabies (n = 100) and ii) dogs vaccinated with the Nobivac Canine Rabies® vaccine (n = 101) four weeks previously. When compared to the gold standard FAVN test, the iELISA was found to be 99% specific and 98% sensitive and there was a significant correlation between the two tests (p < 0.001, r = 0.92). Given these findings, we conclude that the PlateliaTM Rabies II kit ad usum Veterinarium can be considered a valuable tool for the rapid assessment of vaccination status of animals in vaccination programs.

Development and Validation of a Competitive ELISA Based on Bovine Monoclonal Antibodies for the Detection of Neutralizing Antibodies against Foot-and-Mouth Disease Virus Serotype A.

The level of neutralizing antibodies in vaccinated animals is directly related to their level of protection against a virus challenge. The virus neutralization test (VNT) is a "gold standard" method for detecting neutralizing antibodies against foot-and-mouth disease virus (FMDV). However, VNT requires high-containment facilities that can handle live viruses and is not suitable for large-scale serological surveillance. In this study, a bovine broadly neutralizing monoclonal antibody (W145) against FMDV serotype A was successfully produced using fluorescence-based single-B-cell antibody technology. Using biotinylated W145 as a detector antibody and another bovine cross-reactive monoclonal antibody, E32, which was produced previously as a capture antibody, a competitive enzyme-linked immunosorbent assay for the detection of neutralizing antibodies (NAC-ELISA) against FMDV serotype A was developed. The specificity and sensitivity of the assay were evaluated to be 99.04% and 100%, respectively. A statistically significant correlation (r = 0.9334, P < 0.0001) was observed between the NAC-ELISA titers and the VNT titers, suggesting that the NAC-ELISA could detect neutralizing antibodies against FMDV serotype A and could be used to evaluate protective immunity.

Decoding Transcription Regulatory Mechanisms Associated with Coccidioides immitis Phase Transition Using Total RNA.

ABSTRACTNew or emerging infectious diseases are commonly caused by pathogens that cannot be readily manipulated or studied under common laboratory conditions. These limitations hinder standard experimental approaches and our abilities to define the fundamental molecular mechanisms underlying pathogenesis. The advance of capped small RNA sequencing (csRNA-seq) now enables genome-wide mapping of actively initiated transcripts from genes and other regulatory transcribed start regions (TSRs) such as enhancers at a precise moment from total RNA. As RNA is nonpathogenic and can be readily isolated from inactivated infectious samples, csRNA-seq can detect acute changes in gene regulation within or in response to a pathogen with remarkable sensitivity under common laboratory conditions. Studying valley fever (coccidioidomycosis), an emerging endemic fungal infection that increasingly impacts livestock, pet, and human health, we show how csRNA-seq can unravel transcriptional programs driving pathogenesis. Performing csRNA-seq on RNA isolated from different stages of the valley fever pathogen Coccidioides immitis revealed alternative promoter usage, connected cis-regulatory domains, and a WOPR family transcription factor, which are known regulators of virulence in other fungi, as being critical for pathogenic growth. We further demonstrate that a C. immitis WOPR homologue, CIMG_02671, activates transcription in a WOPR motif-dependent manner. Collectively, these findings provide novel insights into valley fever pathogenesis and provide a proof of principle for csRNA-seq as a powerful means to determine the genes, regulatory mechanisms, and transcription factors that control the pathogenesis of highly infectious agents.IMPORTANCE Infectious pathogens like airborne viruses or fungal spores are difficult to study; they require high-containment facilities, special equipment, and expertise. As such, establishing approaches such as genome editing or other means to identify the factors and mechanisms underlying caused diseases, and, thus, promising drug targets, is costly and time-intensive. These obstacles particularly hinder the analysis of new, emerging, or rare infectious diseases. We recently developed a method termed capped small RNA sequencing (csRNA-seq) that enables capturing acute changes in active gene expression from total RNA. Prior to csRNA-seq, such an analysis was possible only by using living cells or nuclei, in which pathogens are highly infectious. The process of RNA purification, however, inactivates pathogens and thus enables the analysis of gene expression during disease progression under standard laboratory conditions. As a proof of principle, here, we use csRNA-seq to unravel the gene regulatory programs and factors likely critical for the pathogenesis of valley fever, an emerging endemic fungal infection that increasingly impacts livestock, pet, and human health.

Inactivation of African Swine Fever Virus by reagents commonly used in containment laboratories

Rapid and effective virus inactivation is an essential step for safe diagnostic testing and for research and vaccine development using infectious viruses. We characterised the reduction of African Swine Fever Virus (ASFV) infectivity using Virkon™ S (Lanxess) 1% w/v disinfectant, FACS™ Lysing buffer (BD), and AVL™ buffer (Qiagen), using porcine cell culture. No virus was detected following a 30 s 20:1 v/v mixing ratio of Virkon™ S 1% with high titre ASFV, supporting its effective use as a laboratory surface disinfectant. FACS™ Lysing and AVL™ buffers also inactivated ASFV, permitting safe removal of treated infected samples from high containment facilities.

Technical and Anatomical Considerations for Reproducible Inactivation of Large Animal Carcasses by Steam Sterilization.

Introduction: The complete inactivation of infectious tissues of large animal carcasses is one of the most challenging tasks in high-containment facilities. Steam sterilization is a method frequently in use to achieve biological inactivation of liquid and solid waste. Objective: This study aims to highlight parameters most effective in creating reproducible cycles for steam sterilization of pig and calf carcasses. Methods: Two pigs or 1 calf were sterilized by running a liquid cycle (n = 3) at 121°C for at least 120 minutes in a pass-through autoclave. To assess the physical and biological parameters, temperature data loggers and biological indicators (BIs) with spores of Geobacillus stearothermophilus (ATCC 7953) were placed at defined positions within animal carcasses. After completion of each cycle, data loggers were analyzed and BIs were incubated for 7 days at 60°C. Results: Initial testing with an undissected pig carcass resulted in suboptimal temperatures at the tissue level with growth on 1 BI. After modifications of the used stainless-steel boxes and by placing the reference probe of the autoclave in the animal carcass, reproducible cycles could be created. A complete inactivation of BIs and a temperature profile of >121°C for at least 20 minutes could be achieved in almost all probed tissues. Conclusion: Only minor modifications in carcass preparation and the used sterilization equipment resulted in effective and reproducible cycles to inactivate large animal carcasses by using a steam autoclave.

Airborne Disinfection by Dry Fogging Efficiently Inactivates Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Mycobacteria, and Bacterial Spores and Shows Limitations of Commercial Spore Carriers.

Airborne disinfection of high-containment facilities before maintenance or between animal studies is crucial. Commercial spore carriers (CSC) coated with 106 spores of Geobacillus stearothermophilus are often used to assess the efficacy of disinfection. We used quantitative carrier testing (QCT) procedures to compare the sensitivity of CSC with that of surrogates for nonenveloped and enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mycobacteria, and spores, to an aerosolized mixture of peroxyacetic acid and hydrogen peroxide (aPAA-HP). We then used the QCT methodology to determine relevant process parameters to develop and validate effective disinfection protocols (≥4-log10 reduction) in various large and complex facilities. Our results demonstrate that aPAA-HP is a highly efficient procedure for airborne room disinfection. Relevant process parameters such as temperature and relative humidity can be wirelessly monitored. Furthermore, we found striking differences in inactivation efficacies against some of the tested microorganisms. Overall, we conclude that dry fogging a mixture of aPAA-HP is highly effective against a broad range of microorganisms as well as material compatible with relevant concentrations. Furthermore, CSC are artificial bioindicators with lower resistance and thus should not be used for validating airborne disinfection when microorganisms other than viruses have to be inactivated.IMPORTANCE Airborne disinfection is not only of crucial importance for the safe operation of laboratories and animal rooms where infectious agents are handled but also can be used in public health emergencies such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We show that dry fogging an aerosolized mixture of peroxyacetic acid and hydrogen peroxide (aPAA-HP) is highly microbicidal, efficient, fast, robust, environmentally neutral, and a suitable airborne disinfection method. In addition, the low concentration of dispersed disinfectant, particularly for enveloped viral pathogens such as SARS-CoV-2, entails high material compatibility. For these reasons and due to the relative simplicity of the procedure, it is an ideal disinfection method for hospital wards, ambulances, public conveyances, and indoor community areas. Thus, we conclude that this method is an excellent choice for control of the current SARS-CoV-2 pandemic.

Adaptation of Research Infrastructure to Meet the Priorities of Global Public Health.

The rise of SARS-CoV-2 has resulted in the urgent need to unlock the mechanisms behind the disease it causes, COVID-19, and to develop countermeasures. As a result, there has been a massive push to study the virus and to test potential candidate vaccines, therapeutics, and antivirals. This has caused a rush at many institutions to switch research priorities to contribute to knowledge about the virus and COVID-19. This means that biosafety professionals have been tasked with figuring out how to conduct research with a novel pathogen safely and securely, often without the requisite knowledge and experience to safely assess the risk. Due to the similarity to another coronavirus, SARS-CoV, many biosafety professionals use the risk mitigation measures for this virus as a starting point. Research with live SARS-CoV-2 requires biosafety level 3 (BSL-3) high containment with additional risk mitigation measures, such as specialized training, engineering controls, personal protective equipment, and health monitoring as well as being mindful of the communication complexities of an ever-connected world. Analyzing human samples, developing diagnostics tests, studying downstream metabolites or proteins, or conducting immunology assays may be performed in a BSL-2 facility with enhanced practices depending upon an institution's risk assessment and risk tolerance. Globally, there are regional differences in high containment laboratories and what is studied in each facility. It is unknown if high-containment laboratory capacity in the United States meets or exceeds the national need or if they can be operated safely (Kingsbury, 2009). In addition, not all BSL-3 facilities are created equal and some do not have the optimal safeguards in place for conducting research with pathogens of pandemic potential. The Government Accountability Office (GAO) previously determined the absence of national standards for high containment laboratory design, construction, commissioning, operations, and maintenance raised concerns and increased the risk of laboratory accidents [US Government Accountability Office (GAO), 2013]. Some BSL-3 laboratories are built for specific purposes and others are built with a limited scope of use. Others are designed in an attempt to anticipate all future uses. More often than not, BSL-3 laboratories are value-engineered due to the high costs of construction, daily-operations, upkeep, and maintenance. Organizations do not want to overspend for features they might not use even though they might need them later on. As a result, there are a limited number of BSL-3 high containment facilities in the United States capable of conducting live SARS-COV-2 research safely and securely, especially with animal models. In addition, not all researchers have the training and expertise to work inside of BSL-3 laboratories. Training programs vary greatly depending on the structure and expertise of the trainer and the previous experiences of researchers. Due to the different designs and resulting standard operating procedures (SOPs), often the training from one facility is not necessarily applicable to another. Although the principles and practices behind biosafety and biosecurity are the same regardless of the design, individuals must demonstrate competency in conducting experiments and the laboratory SOPs before working unescorted. In addition, the COVID-19 pandemic is an ever-evolving situation, and as a result, public health guidance is changing frequently. Currently, there is a greater risk of researchers being exposed to SARS-CoV-2 in the community than from working in the laboratory. In combination, these factors present a challenging environment for biosafety professionals who facilitate research and ensure it is being performed in a safe and secure manner. It takes the entire institutional infrastructure—including but not limited to compliance and safety departments, facilities and maintenance personnel, oversight committees, information technology and security, and media relations—to ensure the research can be brought online swiftly and with limited hindrance in the most effective way possible.

The Use of Arthropod-Borne Challenge Models in BSL-3Ag and BSL-4 Biocontainment.

The study of many arthropod-borne pathogens requires high biosafety considerations, including the use of specialized facilities and equipment for arthropod containment. Mosquito- and tick-borne viruses such as yellow fever, West Nile, and Crimean Congo hemorrhagic fever viruses require facilities that are suitable for housing vertebrates. Multidisciplinary studies that incorporate the vector, vertebrate, and pathogens are essential for a complete understanding of the interactions between these transmission cycle components, especially if they aim to evaluate and model relative susceptibilities of different arthropods and vertebrates to infection and transmission between these. Under laboratory conditions, these studies can be relatively simple, for example, involving colonized arthropods, small animals, and attenuated viruses. Other studies are complex with large animals, high-biocontainment pathogens, and field-collected arthropods. These require a higher level of containment and special design considerations. Both of these types of experiments have their relative merits. A thorough understanding of the issues related to these types of studies and the benefits and drawbacks to using various challenge models will enable the researcher to develop realistic goals for various experiments. This review examines the varied issues that should be considered prior to starting these experiments and covers the basics from the procurement of various arthropods, rearing, high-containment facilities and operational issues specific to work with arthropods, types of infection experiments, and specific issues with arthropod and animal experiments in biosafety levels 3 and 4.

Bioshield: Linking Bioscience, Biosecurity and Strategic Plan for Biodefense in Pandemics

Biological threats, whether intentional, unintentional or natural are considered most dangerous hazards worldwide, seriously affecting the health system and global economy. In 21st century where scientists were busy to create superhuman, COVID-19 outbreak spread to 212 countries, struck the world and we found ourselves ill equipped as international comity to defeat the virus. The economic, health and political foundation were shacked globally and exposed the global health security system due to poor implementations of the policy guidelines. Similarly, Pakistan being an endemic region for emerging and reemerging infectious diseases, encountered badly by numerous different outbreaks in past. Pakistan share border with China, India, Iran and Afghanistan and increase influx of travelers through both air and land route puts Pakistan at high risk to the infectious agents. In 21st century the game of bio warfare cannot be eliminated and pose significant challenges to the security. Countries who learned from past like Korea, China with best preparedness readiness and response tackled the situation as they have best biosecurity, biorisk management system. Biosecurity as biodefense against outbreaks, pandemics, biological warfare and bioterrorism has been underestimated in developing countries like Pakistan and therefore need to highlight the urgency at national level to cope with any future outbreaks. Risk assessment, and mitigation strategies through collaborative work should need to adopt by stakeholders for strategic plan of biosecurity. Better means to protect military, health care workers operating in difficult environment are also needed. A national biosecurity system in response to outbreaks, prioritizing the emergency R&amp;D in diagnostics, establishing high containment facilities, vaccination should be initiated. Moreover, a permanent national defense force or bio-umbrella on biosecurity should be established to shield the country from biological, chemical, nuclear and radiological threat agents. National Biological Defense Program (NBDP) should be initiated to train and protect military personnel against wide range of biological threat.

Polymer microarrays rapidly identify competitive adsorbents of virus-like particles

The emergence of SARS-CoV-2 highlights the global need for platform technologies to enable the rapid development of diagnostics, vaccines, treatments, and personal protective equipment (PPE). However, many current technologies require the detailed mechanistic knowledge of specific material-virion interactions before they can be employed, for example, to aid in the purification of vaccine components or in the design of a more effective PPE. Here, we show that an adaption of a polymer microarray method for screening bacterial-surface interactions allows for the screening of polymers for desirable material-virion interactions. Nonpathogenic virus-like particles including fluorophores are exposed to the arrays in an aqueous buffer as a simple model of virions carried to the surface in saliva/sputum. Competitive binding of Lassa and Rubella virus-like particles is measured to probe the relative binding properties of a selection of copolymers. This provides the first step in the development of a method for the discovery of novel materials with promise for viral binding, with the next being development of this method to assess absolute viral adsorption and assessment of the attenuation of the activity of live virus, which we propose would be part of a material scale up step carried out in high containment facilities, alongside the use of more complex media to represent biological fluids.

Technical and Anatomical Considerations for Reproducible Inactivation of Large Animal Carcasses by Steam Sterilization

Introduction: The complete inactivation of infectious tissues of large animal carcasses is one of the most challenging tasks in high-containment facilities. Steam sterilization is a method frequently in use to achieve biological inactivation of liquid and solid waste. Objective: This study aims to highlight parameters most effective in creating reproducible cycles for steam sterilization of pig and calf carcasses. Methods: Two pigs or 1 calf were sterilized by running a liquid cycle (n = 3) at 121°C for at least 120 minutes in a pass-through autoclave. To assess the physical and biological parameters, temperature data loggers and biological indicators (BIs) with spores of Geobacillus stearothermophilus (ATCC 7953) were placed at defined positions within animal carcasses. After completion of each cycle, data loggers were analyzed and BIs were incubated for 7 days at 60°C. Results: Initial testing with an undissected pig carcass resulted in suboptimal temperatures at the tissue level with growth on 1 BI. After modifications of the used stainless-steel boxes and by placing the reference probe of the autoclave in the animal carcass, reproducible cycles could be created. A complete inactivation of BIs and a temperature profile of &gt;121°C for at least 20 minutes could be achieved in almost all probed tissues. Conclusion: Only minor modifications in carcass preparation and the used sterilization equipment resulted in effective and reproducible cycles to inactivate large animal carcasses by using a steam autoclave.

The Utility of Human Immune System Mice for High-Containment Viral Hemorrhagic Fever Research.

Human immune system (HIS) mice are a subset of humanized mice that are generated by xenoengraftment of human immune cells or tissues and/or their progenitors into immunodeficient mice. Viral hemorrhagic fevers (VHFs) cause severe disease in humans, typically with high case fatality rates. HIS mouse studies have been performed to investigate the pathogenesis and immune responses to VHFs that must be handled in high-containment laboratory facilities. Here, we summarize studies on filoviruses, nairoviruses, phenuiviruses, and hantaviruses, and discuss the knowledge gained from using various HIS mouse models. Furthermore, we discuss the complexities of designing and interpreting studies utilizing HIS mice while highlighting additional questions about VHFs that can still be addressed using HIS mouse models.

Role of Training and Experience in Biosafety Practices Among Nurses Working in Level 2 or 3 Patient Containment.

This study was conducted to assess the difference in biosafety behaviors among nurses working in a levels 2 and 3 hospital unit in Morocco and the need for additional biosafety training before working in a high-containment facility. A prospective cross-sectional and observational study was conducted among new and experienced nurses in the Center of Virology and Tropical Infectious Diseases of the Military Teaching Hospital Mohammed V of Rabat, Morocco, between December 1, 2017 and February 28, 2018 (3 months). We compared behaviors in biosafety practices (donning gloves, handwashing, etc) between the 2 groups, and data were collected by observing workers directly or via camera. A total of 31 nurses, 14 newly graduated nurses (45.2%) and 17 experienced and trained (54.8%) nurses, were observed during 89 entries into high-containment hospital rooms. Among the behaviors observed, only donning an inner pair of gloves was observed consistently between the 2 groups. Experienced and trained nurses washed their hands (100%) and observed the antiseptic contact time (71%), whereas recently graduated nurses ignored these activities significantly (79% and 32%, respectively). During handling of the patient, the trained and experienced nurses were significantly better than the new ones in the practices of biosafety and personal protection. Gaps in biosafety were observed more frequently among newly graduated workers, especially donning outer gloves before patient contact, nurses touching their faces, and the act of wearing jewelry while working. Safety training should begin early in the training curriculum with theoretical and practical courses. It must be introduced into the general biosafety policy as part of a safety and standard working culture. It is recommended that personnel be required to pass a proficiency exam in critical biosafety tasks before working with high-risk patients.

Evaluation of MERS-CoV Neutralizing Antibodies in Sera Using Live Virus Microneutralization Assay.

The microneutralization (MN) assay is a standard and important technique in virology, immunology, and epidemiology. It is a highly specific and sensitive assay for evaluating virus-specific neutralizing antibodies (nAbs) in human and animal sera. It provides the most precise answer to whether or not an individual or animal has antibodies that can neutralize or inhibit the infectivity of a specific virus strain. However, using live virus-based MN assay might require working under high containment facilities especially when dealing with high-risk pathogens such as the Middle East respiratory syndrome-coronavirus (MERS-CoV). In this chapter, we describe the isolation, amplification, and titration of MERS-CoV, as well as detailed MN assay to measure nAb levels in sera from different mammalian species.

Generation of MERS-CoV Pseudotyped Viral Particles for the Evaluation of Neutralizing Antibodies in Mammalian Sera.

Pseudotyped viral particle production has been used extensively and broadly for many viruses to evaluate levels of neutralizing antibodies, viral entry inhibitors and vaccine immunogenicity. This assay is extremely safe and useful alternative to live virus-based assay without the need for high containment facilities. In this chapter, we describe the generation of MERS-CoV pseudotyped viral particles (MERSpp) expressing full-length spike protein using second-generation lentiviral packaging system. This platform is optimized to generate high titer of MERSpp and to test sera from different mammalian species.

Harmonization of Biosafety and Biosecurity Standards for High-Containment Facilities in Low- and Middle-Income Countries: An Approach From the Perspective of Occupational Safety and Health.

Following the global-level Ebola virus disease (EVD) outbreak during 2014–2016, international collaboration with multiorganizational participation has rapidly increased. Given the greater priorities for research and development (R&D) outcomes despite the quantitative and qualitative lack of high-containment laboratory facilities in low- and middle-income countries (LMICs), where biological targets for investigation are located near their natural habitats, occupational readiness for health workers' safety has not been well-addressed, where limited global expert human resources are being deployed to high-containment laboratories including biosafety level 4 (BSL-4) facilities for case management and medical investigations. Pursuing scientific and managerial success to make laboratories efficient and productive, most laboratory safety policies have focused on the functionality of technical skills or performance, procedural methodologies, and supervision over the employees to collaborate in LMICs. The experts dispatched from advanced countries bring a long list of scientific tasks with high-tech devices, supplies, and training programs to introduce their collaboration with local partners in LMICs. However, the dispatched experts would subsequently realize their list becomes endless to establish their basic functions required in high-containment laboratories to ensure qualified scientific outcomes in LMICs. Under such circumstances where dual or multiple policies and standards accommodated pose dilemmas for operational procedures to ensure biosafety and biosecurity, all the frontline experts from both LMICs and advanced countries may be exposed to significant risks of life-threating infection of highly pathogenic agents like EVD, without any pragmatic measures or road maps to establish valued international collaboration, pursuing its sustainability. Given the fact mentioned above, we conducted a quick review of the key biosafety and biosecurity management documents, relevant policy analyses, and research to understand the current status and, if any, measures to dissolve critical dilemmas mentioned above. As a result, we found that occupational safety and health (OSH) aspects had not been sufficiently addressed, particularly in the context of international BSL-4 collaboration in LMICs. Moreover, consideration of OSH can be one of the key drivers to make such collaborative interventions more pragmatic, safer to reorient, harness disease-based vertical approaches, and harmonize policies of biosafety and biosecurity, particularly for collaborations organized in resource-limited settings.

The Insights of Radical Science in the CRISPR Gene-Editing Era: A History of Science for the People and the Cambridge Recombinant DNA Controversy

ABSTRACT In the wake of controversy over human embryonic gene-editing with CRISPR/Cas9 technology, scientists have looked repeatedly to the 1975 Asilomar Conference on Recombinant DNA (rDNA) as a model for adjudicating gene-editing today. However, STS scholars have long critiqued Asilomar as a case of insular scientific self-regulation, and other histories from the early biotech years offer fresh insights for those pursuing an equitable gene-editing landscape in the CRISPR era. Some of the first scientists to approach genetic engineering with a deep understanding of power were the biologists in the radical movement Science for the People (SftP). In 1976, SftP learned that Harvard University was planning to build a high-containment facility for rDNA and fostered a unique moment of democratic technoscientific governance in Cambridge. SftP’s radical framework for regulating rDNA differed from Asilomar’s liberal approach in important ways. While their colleagues at Asilomar ignored the social consequences of rDNA, SftP biologists produced incisive analyses of genetic reductionism, the commercialization of biotechnology, and the public regulation of science – and shared their ideas widely. Along the way, they fostered important intellectual connections with an early community of radical and feminist science studies scholars who were investigating emerging issues around genetic engineering.

Foot-and-mouth disease vaccines: recent updates and future perspectives.

Foot-and-mouth disease (FMD) is a major worldwide viral disease in animals, affecting the national and international trade of livestock and animal products and leading to high economic losses and social consequences. Effective control measures of FMD involve prevention through vaccination with inactivated vaccines. These inactivated vaccines, unfortunately, require short-term protection and cold-chain and high-containment facilities. Major advances and pursuit of hot topics in vaccinology and vectorology are ongoing, involving peptide vaccines, DNA vaccines, live vector vaccines, and novel attenuated vaccines. DIVA capability and marker vaccines are very important in differentiating infected animals from vaccinated animals. This review focuses on updating the research progress of these novel vaccines, summarizing their merits and including ideas for improvement.