News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include expanded monkeypox vaccination efforts; Nipah virus VSV vaccine development; and the expansion of tick-borne diseases into warming areas of North America.
POLICY + GOVERNMENT
Back to the Future for Verification in the Biological Disarmament Regime?
Twenty years after the termination of the Biological and Toxin Weapons Convention (BWC) Ad Hoc Group negotiations, the notion of adopting a BWC verification protocol is now almost an article of faith among some States Parties to the Convention. Yet it is clear that in 2001, the work of the Ad Hoc Group was a long way from agreement around a robust regime capable of ensuring confidence in compliance with the BWC’s prohibitions. Moreover, if there are some elements of continuity in the biosecurity sphere since then, much has also changed – geopolitically, technologically and economically. These changes generate challenges as well as opportunities to strengthen the BWC, which remains a central multilaterally-agreed component of a much wider set of measures that have emerged over the last two decades to prevent the hostile use of biology and manage the challenge of dual use biology around the globe. This report looks at these changes and identifies areas to move forward. United Nations Institute for Disarmament Research (UNIDIR)
WHO Declines to Label Monkeypox a Global Emergency
After 2 days of deliberation, an advisory panel convened by the World Health Organization concluded the monkeypox outbreak that has spread to more than 50 countries does not yet warrant the declaration of a Public Health Emergency of International Concern (PHEIC), its highest alert level. WHO currently has PHEIC declarations for polio and COVID-19, and many infectious disease scientists had expected one for monkeypox. While endemic in many African countries, monkeypox has never before spread so widely on other continents; more than 5800 cases have been recorded so far. Science
U.S. Covid Test Makers Anticipate Layoffs After Government Reallocates Funds
Declining demand for tests had already caused some companies to scale back production, and some said further cuts, as well as layoffs, were probable after White House officials said last week that funding earmarked for testing and personal protective equipment would instead go to buy vaccines and Paxlovid oral antiviral treatment. And it doesn’t look like the White House will be getting more funding to replenish their Covid-19 response accounts from Congress anytime soon. STAT
CDC Opens Monkeypox Center as Europe Begins Vaccinations
The CDC on 28 June activated its Emergency Operations Center (EOC) to better address the monkeypox outbreak. This action stands up the CDC’s command center for monitoring and coordinating the emergency response to monkeypox and mobilizing additional CDC personnel and resources. CIDRAP
Improve CDC’s Quarantine Stations to Prevent the Next Pandemic
A new NASEM report, “Improving the CDC Quarantine Station Network’s Response to Emerging Threats,” offers a roadmap for supporting and strengthening the Division of Global Migration and Quarantine to anticipate and respond effectively to prevent the next pandemic before it takes hold. Included in the key recommendations are expansion of regulatory authority, addressing inadequate staffing issues, overhauling data tools, and the addition of a maritime unit to deal with the cruise ship industry. STAT
MEDICAL COUNTERMEASURES
Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study
Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed. In this Phase 2a study, this RSV bivalent prefusion F (RSVpreF) vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. New England Journal of Medicine
A Cloned rVSV-Vectored Marburg Vaccine Protects Guinea Pigs from Lethal Marburg Virus Disease
Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Study results demonstrated that a single dose of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Vaccines
The U.S. Will Offer Nearly 300,000 Doses of Monkeypox Vaccine in the Coming Weeks
The Department of Health and Human Services will make 296,000 doses available in the coming weeks — within that amount, 56,000 doses will be made available immediately — and expects a total of 1.6 million doses to be available in the U.S. by the end of the year. The vaccine being distributed is the JYNNEOS vaccine, which is administered in two doses given 28 days apart. There are now more than 300 confirmed cases of monkeypox in the U.S., according to the CDC, a likely undercount of actual cases. NPR
Preclinical and Clinical Developments for Combination Treatment of Influenza
The neuraminidase inhibitor class of drugs, including oseltamivir, have been the standard of care for severe influenza illness for many years. The approval of drugs with novel mechanisms of action, such as baloxavir marboxil, broadens potential treatment options for combination therapy. One potential benefit of a combination antiviral treatment strategy is that the combination of drugs with different mechanisms of action may lower the selection of resistance due to treatment. Combination therapy may also become an important treatment option to improve patient outcomes in those with severe illness due to influenza or those that are immunocompromised. This is a summary of preclinical and clinical advances in combination therapy for the treatment of influenza with reference to immunocompromised animal models and clinical data in hospitalized patient cohorts where available. PLoS Pathogens
FDA Calls for Inclusion of Omicron BA.4/5 in Future Boosters
Heeding the advice of its expert advisory committee, the US FDA on Thursday recommended the inclusion of an Omicron BA.4/5 spike protein component in modified COVID-19 vaccine boosters for the upcoming fall and winter seasons. The recommendation follows a 19-2 vote in favor of adding an Omicron-specific component to future boosters by FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) earlier this week. Regulatory Focus
FDA: Don’t Rush a Move to Change the Covid-19 Vaccine Composition
Moderna and Pfizer executives have claimed that the Omicron vaccines will be protective for longer. That may be true, but how long is longer? A few weeks? A month or two? Again, detailed modeling of the data might provide important information. It’s important to be sure that changing the booster vaccine to include the Omicron sequence offers enough of an advantage to justify the cost and complexity associated with making the switch.
The reason why the Omicron and earlier variant boosters are little or no better than a standard booster is rooted in immunology. The immune system responds to the first sight of the viral spike protein by making neutralizing antibodies and by starting to lay down memory cells that are an archive of what it is seeing. Those memory cells improve over a multi-month period and are then triggered into action when the immune system reencounters the spike protein, either as an infection or in a booster vaccination. The resulting neutralizing antibody response doesn’t appear to depend very much on whether the boost was with the original sequence, the Beta sequence, the Delta sequence, or the Omicron sequence — all are about equally as good at reawakening immune memory cells. The Omicron vaccines also seem to elicit some neutralizing antibodies that are unique to that variant and that make a minor contribution to the overall response. It’s possible that component could improve over time or after additional boosts, but we have no data to evaluate. STAT
The Use of Viral Vectors in Vaccine Development
While traditional licensed vaccines consist of either inactivated/attenuated versions of the entire pathogen or subunits of it, most novel experimental vaccines against emerging infectious diseases employ nucleic acids to produce the antigen of interest directly in vivo. These include DNA plasmid vaccines, mRNA vaccines, and recombinant viral vectors. This review presents an overview of pre-clinical and clinical data on recombinant viral vector vaccines and discuss the advantages and limitations of the different viral vector platforms. NPJ Vaccines
Recombinant Vesicular Stomatitis Vaccine Against Nipah Virus Has a Favorable Safety Profile
Nipah virus (NiV) disease is a highly lethal bat-borne virus with epidemic potential causing inflammation of the brain and a severe respiratory syndrome and is a high priority for vaccine development. Researchers here have developed a novel single-dose vaccine that protects animals against disease and death caused by NiV and have started clinical trials. The vaccine is a live, recombinant vesicular stomatitis virus (VSV) vector identical to the recently approved Ebola vaccine (Ervebo) but also expressing the NiV G protein responsible for attachment of the virus to cell receptors. Vaccination results in antibodies to the G protein that block entry of the virus into cells. Since addition of the NiV receptor-binding G protein to a live virus could potentially target it to receptors on brain cells, extensive safety tests for neurovirulence were required involving direct inoculation of the vaccine virus into brains of different animal models. They showed that the vaccine candidate was significantly less neurovirulent in non-human primates than an unrelated approved live viral vaccine against yellow fever which has a long record of safe use and a known incidence of rare neurological adverse events. The findings are important because they illustrate the complexities of phenotypic assessment of novel viral vectors with tissue tropisms determined by transgenic proteins, and because it is unprecedented to use a heterologous comparator virus in a regulatory-enabling study. This approach may have value in future studies of other novel viral vectors. PLoS Pathogens
BIOSECURITY + BIOPREPAREDNESS
Looking for ‘Black Swan’ Outbreaks Can Prepare for Future Pandemics
“Black swan” disease outbreaks —those unexpected outbreaks notable for their duration, spread or severity—share some commonalities that could serve as warning signs of future pandemics or unusually devastating outbreaks. The spread of disease depends on three major factors: One is a pathogen’s ability to adapt to a wide variety of hosts. Another is the population of susceptible hosts that could provide a home for the pathogen. The third is environmental conditions that support — or hinder — the pathogen. STAT
Knowledge and Practice of Nursing Students Regarding Bioterrorism and Emergency Preparedness
Given the essential role of nurses at the frontline of the healthcare system in dealing with bioterrorism and the importance of long-lasting education the present study aimed to compare the effectiveness of simulation and workshop on knowledge and practice of nursing students regarding bioterrorism. The simulation group had better results in terms of enhancing knowledge, preparedness, disaster triage, reporting, incident management, communication and isolation domains compared to the workshop group. BMC Nursing
Agencies Update Guidance for Handling Infectious Waste, Including Monkeypox
Federal agencies have updated their guidance for handling Category A solid waste, including waste that may be contaminated with monkeypox virus, the CDC advised laboratories this week. According to CDC, the current U.S. monkeypox outbreak has so far involved only the ‘West African’ clade of the virus, which can be classified below Category A under the Hazardous Materials Regulations. Department of Transportation
Complementarity of International Instruments in the Field of Biosecurity
Experts have warned for an urgent need to strengthen international arrangements intended to protect the world against chemical, biological, radiological, and nuclear threats. This paper examines in case of full implementation of the International Health Regulations, what other actions states should take to comply with international biosecurity instruments, including the Biological and Toxin Weapons Convention and United Nations Security Council Resolution 1540, to effectively prevent and defend against intentional biological threats. Frontiers in Public Health
SELECT AGENTS + PRIORITY PATHOGENS
The Democratic Republic of the Congo Declares 14th Ebola Outbreak Over
The Democratic Republic of the Congo today declared the end of the Ebola outbreak that erupted less than three months ago in Mbandaka, the capital of Equateur Province in the northwest. It was the third outbreak in the province since 2018 and the country’s 14th overall. With greater experience in Ebola control, national emergency teams, with the support from WHO and partners, mounted a swift response soon after the outbreak was declared on 23 April, rolling out key counter measures including testing, contact tracing, infection prevention and control, treatment and community engagement. Vaccination – a crucial protective measure – was launched just four days after the outbreak was declared. In all, there were four confirmed cases and one probable case – all of whom died. WHO Africa
Natural History of Sudan ebolavirus to Support Medical Countermeasure Development
While licensed therapeutics and vaccines are available in limited number to treat infections of Zaire ebolavirus, there are currently no effective licensed vaccines or therapeutics for SUDV. A well-characterized animal model of this disease is needed for the further development and testing of vaccines and therapeutics. In this study, twelve cynomolgus macaques (Macaca fascicularis) were challenged intramuscularly with 1000 PFUs of SUDV and were followed under continuous telemetric surveillance. Vaccines
Potential Threats to Human Health from Eurasian Avian-Like Swine Influenza A(H1N1) Virus and Its Reassortants
During 2018–2020, researchers isolated 32 Eurasian avian-like swine influenza A(H1N1) viruses and their reassortant viruses from pigs in China. Genomic testing identified a novel reassortant H3N1 virus, which emerged in late 2020. Derived from G4 Eurasian H1N1 and H3N2 swine influenza viruses. This virus poses a risk for zoonotic infection. Emerging Infectious Diseases
Yeast Display Enables Identification of Covalent Single Domain Antibodies Against Botulinum Neurotoxin Light Chain A
Here researchers describe the use of yeast display, a high-throughput protein discovery platform, in combination with noncanonical amino acids (ncAAs) to identify irreversible variants of single-domain antibodies (sdAbs), also called VHHs and nanobodies, targeting botulinum neurotoxin light chain A (LC/A). ChemRxiv (pre-print)
Projecting the SARS-CoV-2 Transition from Pandemicity to Endemicity: Epidemiological and Immunological Considerations
This review discusses the epidemiological dynamics of different viral infections to project how the transition from a pandemic to endemic SARS-CoV-2 might take shape, drawing from theories of disease invasion and transmission dynamics, waning immunity in the face of viral evolution and antigenic drift, and empirical data from influenza, dengue, and seasonal coronaviruses. PLoS Pathogens
Human Monkeypox Study Pinpoints Incubation Period
A preprint by Dutch researchers indicates that the average monkeypox incubation period in the ongoing outbreak is 8.5 days, but it ranged from 4 to 17 days (5th to 95th percentiles)—a slightly narrower window than the CDC has stated. CIDRAP
Dengue Fever and Zika Virus Make Humans More Attractive to Mosquitoes
A new study set out to test whether humans infected with dengue fever and Zika virus are more attractive to mosquitos. Their results show that a chemical produced by bacteria in the skin makes mosquitos more attracted to hosts infected with both flaviviruses. Smithsonian Magazine
Pathogenic Prion Structures at High Resolution
Within the last year and a half, the first 3 near-atomic resolution cryo-EM structures of highly pathogenic brain-derived prions have been reported. This paper highlights how these new prion structures have begun to address fundamental, long-standing questions in prion biology and transmission dynamics. PLoS Pathogens
Participatory Mapping Identifies Risk Areas and Environmental Predictors of Endemic Anthrax in Rural Africa
A combination of GIS tools and participatory approaches yielded information about risk areas and the environmental conditions associated with those areas in a setting hyper-endemic for anthrax. In this study, anthrax occurs mostly in areas characterized by low organic matter and in proximity to water bodies. This suggests that the transmission of B. anthracis to animals likely drives the risk of disease, more than factors that favor the survival of spores in the environment. Interventions for local anthrax control may thus be most effective if targeted towards at-risk areas and livestock management practices that limit transmission to animals. Scientific Reports
Determining the Role of Guanylate-Binding Proteins for Host Defense Against Francisella Tularensis
Due to its intracellular nature, F. tularensis can infect many cell types, but of special relevance is its ability to infect monocytic cells and avoid their otherwise potent antimicrobial effects. Monocytic cells can; however, control infection after activation with IFN-γ, but the molecular mechanisms behind this control are not well understood. Recently, guanylate-binding proteins (GBPs) have been identified as crucial for the control of intracellular F. tularensis and many other bacteria, viruses, and parasites. They represent a vast family of interferon-inducible proteins, but it is incompletely understood how their ubiquitous abilities to control diverse types of infections are executed. The overall aim of the thesis was to obtain a better understanding of how GBPs execute the control of infection caused by Francisella and how the bacterium counteracts the bactericidal effects of the GBPs and of other immune mediators. Digitalia Vetenskapliga Arkivet
CHEMICAL + RADIOLOGICAL THREATS
A Radiological Emergency Health and Safety Plan for City Agencies Without First Response Responsibilities
In the late phase of a radiological incident where components of remediation and recovery have been initiated, other municipal agencies that had not previously planned to respond may be expected to supply various levels of support. In New York City, a Radiological Health and Safety Plan (RHASP) was developed as an appendix to an existing Citywide Health and Safety Plan in order to prepare the personnel of these other agencies to respond to a radiological incident expeditiously. RHASP is designed for an agency-wide health physics program that provides training to understand the hazard; a framework for dosimetry employment; environmental surveillance of the site for worker and public protection; and radioactive waste control. Health Security
Fact Sheet on WMD Threat Reduction Efforts with Ukraine, Russia and Other Former Soviet Union Countries
This Fact Sheet provides an overview of the history of threat reduction and nonproliferation programs supported by the United States, in cooperation with countries of the former Soviet Union, including the Governments of Russia and Ukraine. Defense.gov
SURVEILLANCE + DETECTION
Individual EUAs for Genotyping Tests for SARS-CoV-2
FDA issued an EAU for Labcorp’s VirSeq SARS-CoV-2 NGS Test on the PacBio Sequel II sequencing system. This is the first COVID-19 test to identify specific SARS-CoV-2 Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages. The test is intended to be used when a health care provider decides, based on a patient’s medical history and other diagnostic information, that the test results may help in deciding the appropriate clinical care for the patient (e.g. most efficacious antiviral or therapeutic antibody treatment). FDA
Avian Flu’s Toll on Wild Birds Alarms Experts
This year’s outbreak of the H5N1 virus has resulted in the deaths of nearly 400,000 wild birds worldwide. The count may be a vast underestimate because of how difficult it is to track sick and dead birds. The toll wrought by this H5N1 strain on wild birds — it has struck more than 100 species so far — has been alarming and unprecedented in its depth and breadth. Among wild birds, the spread can be very difficult to contain, posing a greater threat of spillover to other wildlife. And some wild bird species, like cranes and some seabirds, are particularly vulnerable, especially those with low reproductive rates and those already endangered. New York Times
Natural Reassortment of Eurasian Avian-Like Swine H1N1 and Avian H9N2 Influenza Viruses in Pigs, China
Several zoonotic influenza A viruses (IAVs) detected in humans contain genes derived from avian H9N2 subtypes. Researchers here uncovered a Eurasian avian-like H1N1 swine influenza virus with polymerase basic 1 and matrix gene segments derived from the H9N2 subtype, suggesting that H9N2 viruses are infecting pigs and reassorting with swine influenza viruses in China. Emerging Infectious Diseases
Climate Change Influences on the Geographic Distributional Potential of the Gulf Coast Tick and Rocky Mountain Wood Tick
Amblyomma maculatum (Gulf Coast tick), and Dermacentor andersoni (Rocky Mountain wood tick) are two North American ticks that transmit spotted fevers (Rickettsia, Francisella tularnesis, Coltivirus, Anaplasma marginale). Here, researchers used ecological niche modeling (ENM) to assess the potential geographic distributions of these two medically important vector species in North America under current condition and then transfer those models to the future under different future warming climate scenarios with special interest in highlighting new potential expansion areas. New potential for range expansions was anticipated for both tick species northward in response to climate change, extending across the Midwest and New England for A. maculatum, and still farther north into Canada for D. andersoni. PeerJ
The Development of Diagnostic Immunoassays for Melioidosis and Ebola Virus Disease
This dissertation outlines alternative approaches to enhance the detection of B. pseudomallei capsular polysaccharide (CPS) on Lateral flow immunoassay (LFI) as well as outlines the development of a LFI prototype for the rapid diagnosis of early EVD through detection of Ebola virus soluble glycoprotein (sGP). The Active Melioidosis Detect Lateral Flow Immunoassay (AMD LFI) was developed by in collaboration with InBios International, Inc. to diagnose melioidosis through the detection of CPS, a biomarker of the disease, using a sample enrichment protocol for improved clinical detection results. University of Nevada, Reno
Fluorescent Biosensors for the Detection of Viruses Using Graphene and Two-Dimensional Carbon Nanomaterials
Two-dimensional carbon nanomaterials have been commonly employed in the field of biosensors to improve their sensitivity/limits of detection and shorten the analysis time. These nanomaterials act as efficient transducers because of their unique characteristics, such as high surface area and optical, electrical, and magnetic properties, which in turn have been exploited to create simple, quick, and low-cost biosensing platforms. In this review, graphene and two-dimensional carbon material-based fluorescent biosensors are covered between 2010 and 2021, for the detection of different human viruses. This review specifically focuses on the new developments in graphene and two-dimensional carbon nanomaterials for fluorescent biosensing based on the Förster resonance energy transfer (FRET) mechanism. The high-efficiency quenching capability of graphene via the FRET mechanism enhances the fluorescent-based biosensors. The review provides a comprehensive reference for the different types of carbon nanomaterials employed for the detection of viruses such as Rotavirus, Ebola virus, Influenza virus H3N2, HIV, Hepatitis C virus (HCV), and Hepatitis B virus (HBV). Biosensors
SPECIAL INTEREST
Nancy Messonnier Named Dean of Gillings School of Global Public Health
Dr. Nancy Messonnier has been appointed dean of the UNC Gillings School of Global Public Health, effective Sept 1. Messonnier began her public health career in 1995 at the CDC as an epidemic intelligence officer and held several leadership posts at the CDC, including first as deputy director and then as director of the National Center of Immunization and Respiratory Diseases from 2014-2021. University of North Carolina at Chapel Hill
Also Reading:
Comparative value-based pricing of an Ebola vaccine in resource-constrained countries based on cost-effectiveness analysis. Journal of Medical Economics
ThioredoxinA1 Controls the Oxidative Stress Response of Francisella tularensis Live Vaccine Strain (LVS). Journal of Bacteriology
There’s a shortage of monkeypox vaccine. Could one dose instead of two suffice? Science
A Contactless IoT-Based GPS-Tracked Waste Bin to Curb Medical Waste Infections in Ghana. African Journals Online
Dissertation: Movement, mobility and disease modelling in three epidemic contexts. Edinburgh Research Archive
Regulatory Networks Controlling Neurotoxin Synthesis in Clostridium botulinum and Clostridium tetani. Toxins
Draft Genome Sequence of Clostridium botulinum Subtype bont/A5(B2′). Microbiology Resource Announcements
A case report of ulceroglandular tularemia caused by Francisella tularensis subsp. holarctica in Iran. Acta Tropica
Strengthening Vaccines and Medicines Manufacturing Capabilities in Africa: Challenges and Perspectives. EMBO Molecular Medicine
Integrated end-to-end MVA viral vector production: Perfusion culture shows economical advantage over batch culture. ECI Digital Archives
Antibodies to combat viral infections: development strategies and progress. Nature Reviews Drug Discovery