News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include West Africa’s first Marburg case; GAO’s findings on shortfalls in U.S. biodefense preparedness; a halt to prion research in France after lab worker exposures; and the urgent need for a correlate of protection for SARS-CoV-2 vaccines.
POLICY + INITIATIVES
After-Action Findings and COVID-19 Response Revealed Opportunities to Strengthen Preparedness
GAO’s analysis of after-action reports for selected interagency biological incident exercises and real-world incidents, as well as the COVID-19 response, identified long-standing biodefense challenges. The U.S. lacked elements necessary for preparing for nationally significant biological incidents, including a process at the interagency level to assess and communicate priorities for exercising capabilities. GAO determined that agencies do not routinely work together in monitoring results from exercises and real-world incidents to identify patterns and root causes for systemic challenges. GAO
Key Accomplishments and Priorities of the National Biodefense Strategy
Examples highlighted include: moving towards influenza vaccine modernization with launch of first universal flu vaccine clinical trial; launch and promotion of ASPR’s S3: Science, Safety, Security resource portal to increase biosecurity and biosafety communication; planning guidance from HHS for handling solid waste contaminated with Category A infectious substance; Antimicrobial Resistance Challenge commitments; One Health toolkit; and Community Mitigation Framework for local COVID-19 mitigation strategies. NACCHO
Don’t Restrict Valid Pathogen Research, ASM & Partners Warn Congress
ASM and partner organizations issued a letter to the House Appropriations Committee urging them to reject attempts to impose restrictions on federally funded research or the operations of federal science agencies based on premature conclusions about how the pandemic emerged. Such efforts could have serious, negative unintended consequences for potentially lifesaving research. American Society for Microbiology
W.H.O. Experts Seek Limits on Human Gene-Editing Experiments
Their recommendations, made after two years of deliberation, aim to head off rogue science experiments with the human genome, and ensure that proper uses of gene-editing techniques are beneficial to the broader public, particularly people in developing countries, and not only the wealthy. The New York Times
HHS Further Amends Declaration Under the PREP Act to Address Influenza and COVID-19 Impact and Add Pharmacist Vaccinators
Influenza season requires many people to be vaccinated within a short period of time, potentially creating a surge on the system, concurrent with COVID-19 vaccination demands. The eighth amendment to the Declaration Under the Public Readiness and Emergency Preparedness Act (PREP Act) for Medical Countermeasures Against COVID–19 adds and/or clarifies that pharmacy interns and technicians, under proscribed circumstances, can aide in the vaccination efforts. JD Supra
Unvaccinated Health Workers Are “Unethical and Appalling”—Experts Want Mandates
Seven major health organizations—including the Society for Healthcare Epidemiology of America, the Association for Professionals in Epidemiology and Infection, the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society—published a consensus statement, saying that “COVID-19 vaccination should be a condition of employment for all healthcare personnel.” While more than 96 percent of physicians reported being fully vaccinated, the numbers are lower for other types of staff and vary by region, and only 55 percent of nursing home staff have been vaccinated nationwide. ARS Technica
MEDICAL COUNTERMEASURES
A Correlate of Protection for SARS-CoV-2 Vaccines is Urgently Needed
Recent studies suggest that neutralizing antibodies could serve as a correlate of protection for vaccines against SARS-CoV-2 in humans. Having an established correlate of protection would allow healthcare providers to manage the vaccination of immunocompromised individuals more efficiently, provide a more cost-effective path to vaccine development based on immune readouts, and would also allow healthcare and governing bodies to efficiently determine what percentage of the population is protected. Although seroprevalence is currently used as a crude measure of community immunity, having a correlate of protection would allow more-precise estimations that could then trigger interventions. Nature Medicine
Adenoviral Vector Vaccine Platforms in the SARS-Cov-2 Pandemic
In addition to mRNA vaccines, the most advanced technology for COVID-19 vaccines is Ad vectors. This review details those currently in human clinical trials and provides an overview of the new technologies employed in their design. NPJ Vaccines
Why Cuba Developed Its Own Covid Vaccine—And What Happened Next
Rather than negotiating with pharmaceutical giants or the Covax vaccine sharing initiative, Cuba bet everything on its prestigious biotech sector coming up with its own vaccine against covid-19. And though the gamble has been shrouded in mystery and met with scepticism, it could be paying off. The BMJ
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. New England Journal of Medicine
Hot Vax Summer? Pfizer’s Mood-Killing, Premature Booster Announcement
Pfizer’s chief scientific officer Mikael Dolsten told Reuters that six months after getting the Pfizer shot, “there likely is the risk of reinfection as antibodies, as predicted, wane.” The company planned to ask the US government to authorize a third shot of its near-miraculous vaccine and even test a new vaccine specifically tailored to the new highly contagious delta variant of the coronavirus causing the pandemic. Bulletin of the Atomic Scientists
Global COVID-19 Vaccine Inequity: Scope, Impact and Challenges
Only 5% of the world has received one dose of the vaccine, and the inequities are even more profound in areas such as the continent of Africa where most countries have administered doses to less than 1% of their population. While initiatives such as COVAX have made some progress in mitigating inequitable vaccine distribution, these efforts currently appear insufficient to address the scale of global need. Cell Host & Microbe
The mRNA Vaccines Are Extraordinary, but Novavax Is Even Better
Maryland-based biotech firm Novavax announced its latest stunning trial results last week, and an efficacy rate of more than 90 percent even against coronavirus variants. The Novavax data confirm that it’s possible to achieve efficacy against COVID-19 with a more familiar technology, that some people may be inclined to trust, that’s also easier to manufacture. The Atlantic
Novavax Says U.S. Will Pause Funding for Production of Its Vaccine
Although the company reported in June that its vaccine had an efficacy of 90 percent against symptomatic Covid-19 cases, and 100 percent against severe disease, Novavax has struggled for months to mass manufacture its product. Its vaccine has not been authorized for distribution in the United States, and federal officials said it is unclear when or if it will be. New York Times
BIOSECURITY + BIOPREPAREDNESS
US Health Security at Risk Because of Medicine Manufacturing Limits
In the US, no manufacturing source exists for more than 80% of the active ingredients in medicines the FDA deems essential for public health – creating an incredible vulnerability to the public health care system and health security. Of 52 COVID-related medicines, 75% had no US source of active pharmaceutical ingredients (APIs). Of the 47 most-prescribed antivirals, 97% had no US source of API. Of the 111 most-prescribed antibiotics, 92% have no US source of API. Of the top 100 generic medicines consumed in the US, 83% had no US source of API. WUSTL
France Issues Moratorium on Prion Research After Fatal Brain Disease Strikes Two Lab Workers
Five public research institutions in France have imposed a 3-month moratorium on the study of prions—a class of misfolding, infectious proteins that cause fatal brain diseases—after a retired lab worker who handled prions in the past was diagnosed with Creutzfeldt-Jakob disease (CJD), the most common prion disease in humans. An investigation is underway to find out whether the patient, who worked at a lab run by the National Research Institute for Agriculture, Food and Environment (INRAE), contracted the disease on the job. Science
Known and Unknown Transboundary Infectious Diseases as Hybrid Threats
The pathogenicity, transmissibility, environmental stability, and potential for genetic manipulation make microbes hybrid threats that could blur the distinction between peace and war. These agents can fall below the detection, attribution, and response capabilities of a nation and seriously affect their health, trade, and security. A framework that could enhance horizon scanning regarding the potential risk of microbes used as hybrid threats requires not only accurately discriminating known and unknown pathogens but building novel scenarios to deploy mitigation strategies. Frontiers in Public Health
Is Genetic Engineering Unleashing Threat of Increased Bioterrorism and Biological Warfare?
As the realm of genetic engineering has advanced, tailored development of lethal and contagious pathogens is feasible, rendering biodefense a challenging phenomenon. The dark side of biotechnology or ‘black biology’ has made it attainable to create ‘designer genes’ that can be exploited as lethal bioweapons. Genetic Literacy Project
Tennessee’s Former Top Vaccine Official: ‘I Am Afraid for My State’
“Today I became the 25th of 64 state and territorial immunization program directors to leave their position during this pandemic. That’s nearly 40% of us. And along with our resignations or retirements or, as in my case, push from office, goes the institutional knowledge and leadership of our respective COVID-19 vaccine responses. I will not sit quietly by while our public health infrastructure is eroded in the midst of a pandemic.” Tennessean
SELECT AGENTS + CBRNE THREATS
Guinea Records Probable Case of Marburg Virus
A probable case of Marburg virus, a deadly hemorrhagic fever similar to Ebola, has been detected in southeastern Guinea’s Nzerekore health district, near the borders with Liberia and Ivory Coast. Two national laboratories based in Guéckédou and Conakry confirmed the identification. The samples have been sent to Pasteur Institute in Dakar, Senegal, a higher level lab, for confirmation.This would represent the first case of human Marburg in West Africa. Nzerekore experienced an Ebola outbreak earlier this year in which 23 cases, including 12 deaths, were registered. It was also where West Africa’s 2013-2016 Ebola outbreak, the largest ever, began before sweeping through Liberia and Sierra Leone. Reuters, Forbes
Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response
This report provides CDC recommendations regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Y. pestis is categorized as a Tier 1 bioterrorism Select Agent, due in part to its low infectious dose, high case-fatality rate in untreated infection, and history of use as an agent of bioterrorism. The most concerning scenario involves dispersing Y. pestis into the air, leading to primary pneumonic plague among exposed persons. The WHO has estimated that a release of 50 kg of Y. pestis into the air over a city of 5 million persons could result in 150,000 cases of pneumonic plague and 36,000 deaths. Moreover, infection of animals after such an attack could spark a local epizootic, resulting in primary bubonic plague among persons who handle infected animal carcasses or are bitten by infected fleas. MMWR
In Vivo Activity of Repurposed Amodiaquine as a Host-Targeting Therapy for the Treatment of Anthrax
Antimalarial amodiaquine acts as a host-oriented inhibitor of anthrax toxin endocytosis. nearly doubled the survival of mice infected subcutaneously with a B. anthracis LD60. Surprisingly, the anthrax efficacy of antimalarial amodiaquine relies on an additional host macrophage-directed antibacterial mechanism, which was validated in the toxin-independent Drosophila model of Bacillus infection. The results support further experiments on AQ as an adjunctive anthrax treatment. ACS Infectious Diseases
A Trans-Agency Workshop on the Pathophysiology of Radiation-Induced Lung Injury
Research and development of medical countermeasures (MCMs) for radiation-induced lung injury relies on the availability of animal models with well-characterized pathophysiology, allowing effective bridging to humans. To develop useful animal models, it is important to understand the clinical condition, advantages and limitations of individual models, and how to properly apply these models to demonstrate MCM efficacy. Radiation Research
Europe Isn’t Ready for Russian Chemical and Biological Warfare
In NATO, CBRN training has lapsed. While Czechia (Czech Republic) retains one of the only live-agent chemical weapons training facilities in NATO, there is far less focus on the CBRN threat in NATO nations, in both civil defense and military settings. While Russia has upgraded its CBRN reconnaissance vehicles twice since the 2000s, the United States last procured an upgrade for its German M93 Fox CBRN reconnaissance vehicles in 2007. National Interest
Posttranslational Regulation of Botulinum Neurotoxin
Botulinum neurotoxin (BoNT) is a public health and bioterrorism concern as well as an important and widely used pharmaceutical, yet the regulation of its synthesis by BoNT-producing clostridia is not well understood. This paper highlights the role of environmentally controlled posttranslational regulatory mechanisms influencing processing and stability of biologically active BoNTs produced by C. botulinum. The results of this work will help enhance public health and safety measures and our ability to evaluate safety risks of novel BoNTs and improve production and quality of BoNTs for pharmaceutical use. mBio
Acoustofluidic Device for Capture of Bacillus Anthracis Spore Analogues at Low Concentration
A portable device for the rapid concentration of spores using a thin-reflector acoustofluidic configuration which can be cheaply and robustly manufactured and provide a more reliable acoustic force than previously explored quarter-wave resonator systems. The Journal of the Acoustical Society of America
Detection of Yersinia pestis by Portable Cas12a-UPTLFA Platform
Due to high infectivity and mortality, as well as the potential to be misused as bioterrorism agent, a culture-free, ultrasensitive, specific, and rapid detection method for Y. pestis has long been desired. Here researchers present a novel system composed of Cas12a-based nucleic acid detection and up-converting phosphor technology (termed Cas12a-UPTLFA) for rapid detection of Y. pestis. Frontiers in Microbiology
SURVEILLANCE + DETECTION
Biological Warfare Canaries
In the face of germ warfare, just knowing you are under attack is half the battle. Once a year a select group of scientists and engineers gathers at Dugway Proving Ground for an unusual showdown: to field-test their systems for detecting biological warfare agents. Shortly before the trial gets under way, the competitors make final adjustments to their devices and then retire to trailers nearly a kilometer away. Moments later, an aerosol cloud containing spores of Bacillus globigii is released into the air about 90 meters from the devices. This is no idle contest; this is serious business, critical to national security. IEEE Spectrum
A Global Nucleic Acid Observatory for Biodefense and Planetary Health
Researchers propose a global Nucleic Acid Observatory (NAO) to monitor the relative frequency of everything biological through comprehensive metagenomic sequencing of waterways and wastewater. By searching for divergences from historical baseline frequencies at sites throughout the world, NAO could detect any virus or invasive organism undergoing exponential growth whose nucleic acids end up in the water, even those previously unknown to science. Continuously monitoring nucleic acid diversity would provide us with universal early warning, obviate subtle bioweapons, and generate a wealth of sequence data sufficient to transform ecology, microbiology, and conservation. arXiv (pre-print)
The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses
Although currently understudied, H6Nx avian influenza viruses pose a substantial threat to both poultry and human health, and are being detected globally with increasing frequency. Some H6Nx lineages are becoming enzootic in Asian poultry and sporadic incursions into European poultry are occurring more frequently. H6Nx viruses that contain mammalian adaptation motifs pose a zoonotic threat and have caused human cases. Viruses
Veterinary Intelligence: Integrating Zoonotic Threats Into Global Health Security
Ignoring the potential for animal infections to produce and propagate human disease is a failure of health security. The siloing of veterinary and medical communities obstructs the development of an effective health security research agenda and training pathways that promote collaboration and synergistic working in these domains. Integration, not only within a One Health agenda, but in a systematised health security intelligence framework opens up horizons for a more holistic disease preparedness system, able to detect and respond to an array of infectious disease threats from novel viruses to AMR whether they emerge in animals or humans. Journal of Royal Society of Medicine
Performance of Saliva and Mid-turbinate Swabs for Detection of Variants of Concern
When moving from wildtype SARS-CoV-2 to the Beta variant-of-concern, the positive percentage agreement (PPA) of saliva swabs with nasopharyngeal swabs increased by 21 percentage points, whereas the PPA for mid-turbinate swabs relative remained similar. Why the improvement in saliva but not mid-turbinate samples? The findings suggest that established diagnostic methods might require re-validation with the emergence of novel variants. Further analysis is underway to determine whether the beta VOC is associated with compartmentalized replication, distinct oral shedding dynamics, increased viral burden, and increased infectious duration. The Lancet Infectious Diseases
HISTORICAL REFLECTIONS
Historical Political Opposition to Bioweapons Verification
Nations have been unable to agree on how to strengthen the BWC, and in particular, verification mechanisms. An effective bioweapons verification process would require nations to identify a large number of civilian facilities. Inspectors would need to monitor them regularly. The monitoring would need to be intrusive, allowing inspectors to demand “challenge inspections,” meaning access on short notice to both known and suspected facilities. Developing bioweapons defenses – as permitted under the treaty – typically requires working with dangerous pathogens and toxins, and even delivery systems. So distinguishing legitimate biodefense programs from illegal bioweapons activities often comes down to intent – and intent is hard to verify. Brandeis Now
1967 Chemical and Biological Warfare – The Weapons and Policies
Useful attributes of chemical and biological agents, from a military point of view, are that they can penetrate structures, cover large areas, and produce a range of effects for varying periods – severe illness for a brief time or less-severe illness for a long time, tears or hallucinations, paralysis or death. A useful quality of biological weapons, according to the unclassified military field manual FM 3-10, is their ability to “accomplish their effects…with little or no physical destruction. This constitutes an advantage both in combat operations… and – from a longer-range viewpoint – in postwar rehabilitation, where overall rebuilding requirements would be reduced.” Science
1969 Symposium on Chemical and Biological Warfare
The decision to confine (U.S.) biological research to defensive measures such as immunization and safety measures largely or completely removes the need for secrecy at the U.S. Army Biological Laboratories at Fort Detrick, Maryland and opens the way for the application of its substantial resources to the solution of such outstanding problems as the elimination of infectious disease, biological insect control, and the application of microbiology to the abatement of pollution. / Once chemical weapons enter military inventories and once the long-observed rule of “no gas” is abandoned, there is no unique and equally simple standard for agreement on where to hold the line. The largescale military employment of anti-plant chemicals poses special ecological and public health problems of its own, regarding which we still know very little. PNAS