News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include strengthening the biomanufacturing supply chain, wide-area biological agent detection systems, animal models for Influenza A, and an overview of vaccine carriers to induce mucosal immunity.
POLICY + GOVERNMENT
BARDA Selects Management Firm for New Biopharmaceutical Manufacturing Preparedness Consortium
BARDA has selected Advanced Technology International (ATI) as the new Biopharmaceutical Manufacturing Preparedness Consortium (BioMaP-Consortium) management firm. The Consortium is a new 10-year program to improve domestic capabilities to manufacture and deliver vital medical countermeasures by bringing together industry partners across the biomanufacturing supply chain. MedicalCountermeasures.gov
Citing Misinformation, Florida Health Official Calls for Halt to Covid Vaccines
Florida’s surgeon general on Wednesday called for a halt to the use of Covid vaccines, citing widely debunked concerns that contaminants in the vaccine can permanently integrate into human DNA. Dr. Joseph Ladapo was appointed surgeon general in 2021 by Gov. Ron DeSantis, a Republican, and has since increasingly aligned himself with anti-vaccine claims that the shots cause serious harm. New York Times
Virology—The Path Forward
In the first 23 years of the 21st century, we have already been confronted with two pandemics (H1N1 influenza virus and COVID-19) and at least four major viral outbreaks (SARS, MERS, Zika, and Ebola). Well-developed and implemented oversight in pathogen research is crucially important; however, implementation of the proposed NSABB recommendations will leave the US more vulnerable to future viral outbreaks. New oversight must not impede the scientific mission of identifying and addressing well-evidenced natural threats. Journal of Virology
Global Health Security Partnerships Annual Progress Report
This report highlights the Administration’s actions to accelerate implementation of the National Biodefense Strategy and Implementation Plan for Countering Biological Threats, Enhancing Pandemic Preparedness, and Achieving Global Health Security. By 2025, the U.S. is committed to directly supporting at least 50 countries to strengthen and achieve regional, national and local capacity in five critical areas to prevent, detect, and respond to infectious disease threats. WhiteHouse.gov
MEDICAL COUNTERMEASURES
Efficacy of Different AV7909 Dose Regimens in a Nonclinical Model of Pulmonary Anthrax
The vaccine AV7909, consisting of the licensed anthrax drug substance AVA adjuvanted with CpG7909, induces high levels of toxin neutralizing antibodies in healthy adults using fewer doses than AVA. This study compares the ability of one- or two-dose regimens of AV7909 to induce a protective immune response in guinea pigs challenged with a lethal dose of aerosolized B. anthracis spores 6 weeks after the last vaccine dose. Human Vaccines and Immunotherapeutics
Comparative Pathology of Animal Models for Influenza A Virus Infection
Animal models are essential for studying disease pathogenesis and to test the efficacy and safety of new vaccines and therapeutics. For most diseases, there is no single model that can recapitulate all features of the human condition, so it is vital to understand the advantages and disadvantages of each. The purpose of this review is to describe popular comparative animal models, including mice, ferrets, hamsters, and non-human primates (NHPs), that are being used to study clinical and pathological changes caused by influenza A virus infection with the aim to aid in appropriate model selection for disease modeling. Pathogens
Tubeimosides are Pan-Coronavirus and Filovirus Inhibitors
SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. This paper details screening of 974 natural compounds and identification of Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Of six NPC1 inhibitors tested, they all blocked EBOV entry, but only Tubeimosides strongly inhibited SARS-CoV-2 infection. Researchers also found that the VSV and EBOV entry are more sensitive to the lysosomotropic agents than SARS-CoV-2, which supports that unlike VSV and EBOV, SARS-CoV-2 could use alternative routes for infection. Nature Communications
Use of Real-World EMR Data to Rapidly Evaluate Treatment Effects of Existing Drugs for Emerging Infectious Diseases
Most of the medications thrown at the novel coronavirus in 2020 have proven to be ineffective or only marginally effective to treat COVID-19 by more rigorous RCT or secondary data analyses later. Here researchers propose to use real-world electronic medical records (EMR) data to develop real-time treatment evaluation and monitoring systems to identify effective treatments or avoid ineffective treatments for emerging diseases in the future. Statistics in Biosciences
Antigen Self-Anchoring Onto Bacteriophage T5 Capsid-Like Particles for Vaccine Design
The promises of vaccines based on virus-like particles stimulate demand for universal non-infectious virus-like platforms that can be efficiently grafted with large antigens. The capsid of bacteriophage T5 offers major advantages for Ag display and vaccination. The procapsid form, devoid of DNA, is easy to produce and to maturate into a capsid-like particle (CLP) with the same structure, stability and affinity for the decoration protein pb10 compared to the native virion. NPJ Vaccines
The Role of Engineered Materials in Mucosal Vaccination Strategies
Mucosal vaccines need to penetrate the mucus layer, reach the target tissue and activate robust immune responses in the mucosal tissues. This review provides an overview of current mucosal vaccines, and discusses the different classes of materials currently being used as vaccine carriers to induce antigen-specific mucosal immunity, including lipids, natural and synthetic polymers, inorganic materials and pathogen-inspired materials. Nature Reviews Materials
BIOSECURITY + BIOPREPAREDNESS
Laboratory Accidents and Biocontainment Breaches
This paper discusses the findings of a new review of all reports of laboratory accidents worldwide that were published between 2000 and 2021. The review highlights that few countries require the reporting of laboratory accidents, and that what is reported is a significant understatement of the scale of the problem. Chatham House
Plagues, Cyborgs, and Supersoldiers
The authors of this report examine the existing and potential future uses of biotechnology in warfare and battle and look at the human body as a warfighting domain. They envision a future in which biotechnology is used by both state and nonstate actors to affect warfighting. Sophisticated future actors may use pathogens, brain-computer interfaces (BCIs), genomic enhancements, and wearable technology to supplement and strengthen warfighters. Rand
Kansas Highly Infectious Disease and Pandemic Plan 2024
To prepare for the next pandemic, the Kansas Department of Health and Environment (KDHE), in cooperation with local and state partners, has developed this Kansas Highly Infectious Disease and Pandemic Plan, which provides an overview of strategies to reduce highly infectious disease or pandemic related morbidity, mortality, and social disruption in the state. Kansas Department of Health and Environment
SELECT AGENTS + PRIORITY PATHOGENS
Dissecting Pandemic-Prone Viral Families – Volume 1: The Picornaviridae
Of concern is the observation that non-pharmaceutical interventions (NPIs) put in place to slow the spread of SARS-CoV-2 – which belongs to the Coronaviridae family – did not suppress the spread of key viruses in the Picornaviridae family (which includes rhinoviruses and enteroviruses) as markedly as they did for other virus families. Often, infected individuals with minimally symptomatic disease can perform their activities of daily living while contagious to others. There is real concern that an uncharacterized member of this family may emerge with the ability to cause widespread severe disease or that a previously identified member with concerning features may acquire the ability to spread more widely. Center for Health Security
Establishment of a Novel Minigenome System for the Identification of Drugs Targeting Nipah Virus Replication
This study aimed to develop two minigenome systems (transient and stable expression) based on a helper cell line expressing the NiV P, N and L proteins required to initiate NiV RNA replication. Stable minigenome cells were resistant to ribavirin, remdesivir and favipiravir but sensitive to interferons. Microbiology Society
Domestic Pigs are Susceptible to Experimental Infection with NHP-Derived Reston Virus Without the Need for Adaptation
Pork consumption has driven the intensification of pig production expanding into environments conducive to increased emergence and spread of infectious diseases, including the spillover of pathogens into human populations. One of these emerging viruses, Reston virus (RESTV), is an enigma among the Orthoebolavirus genus in that its lack of human pathogenicity is in stark contrast to the high virulence associated with most other ebolaviruses. RESTV is, however, associated with outbreaks of highly lethal hemorrhagic disease in non-human primates (NHP), as well as poorly understood clinical manifestations of mixed virulence and lethality in naturally and experimentally infected domestic pigs. These results show it is possible for RESTV derived from an NHP to infect domestic pigs resulting in a spectrum of disease, from asymptomatic to severe respiratory distress. Scientific Reports
AVIAN INFLUENZA
Avian Flu Strikes More US Poultry in 5 States
Five states reported more highly pathogenic avian influenza outbreaks in poultry over the last few days, including California where more layer farms were hit by the virus. Since the H5N1 outbreaks in US poultry began in February 2022, the events have led to a loss of a record 79.7 million birds across 47 states. CIDRAP
First Case of Lethal Bird Flu in Polar Bears Reported in Alaska
A highly lethal form of bird flu that has been spreading across the world has now been detected in a dead polar bear in Alaska. It is the first known case in the Arctic animals, which are listed as threatened under the Endangered Species Act. Alaska has previously reported infections in a brown bear and a black bear, as well as in several red foxes. “The number of mammals reported with infections continues to grow.” New York Times
CHEMICAL + RADIOLOGICAL THREATS
Prediction of Acute Toxicity (LD50) for Organophosphorus-Based Chemical Warfare Agents Using Toxicology In Silico Methods
Estimation was performed using in silico software: Toxicity Estimation Software Tool (TEST), QSAR Toolbox, and ProTox-II. Toxicology findings provide the first comprehensive information on the acute toxicity (LD50, rat, oral) of many V agents. Archives of Toxicology
Development of Drug Products for the Treatment of Acute Radiation Syndrome
The successful development of countermeasures to radio-nuclear threats that cause Acute Radiation Syndrome (ARS) provides the opportunity to explore potential areas of overlap in the scientific approaches to studies of injuries caused by radiation and sulfur mustard exposures in animals. The aim is to evaluate the available scientific knowledge for radiation threat agents and sulfur mustard for potential analogies of fundamental mechanisms of organ injury and dysfunction. Disaster Medicine and Public Health Preparedness
SURVEILLANCE + DETECTION
Blackett Review on Wide-Area Biological Detection
This report identifies a number of technologies and capabilities that could improve government’s ability to detect and respond to an airborne biological attack or infectious disease outbreak. Whilst the review focused on the detection of a deliberate release of a biological agent, the panel concluded that the ability to rapidly detect unusual health signals would have significant benefits for public health. UK Government Office for Science
Uganda Spots Anthrax Outbreak Early Via Enhanced Situational Awareness
In October 2023, anthrax broke out in Uganda and several other East African countries, several months earlier than the usual peak in January and February, when those regions transition from a dry to rainy season. The current outbreak has also hit regions not prone to anthrax. But earlier in the year, before the anthrax season could surge, authorities got a head start by using existing data in new ways. Think Global Health
Inferring Incidence of Unreported SARS-CoV-2 Infections Using Seroprevalence of Open Reading Frame 8 Antigen
Researchers tested seroprevalence of open reading frame 8 antigens to infer the number of unrecognized SARS-CoV-2 Omicron infections in Hong Kong during 2022. Estimated 33.6% of the population was infected, 72.1% asymptomatically. Surveillance and control activities during large-scale outbreaks should account for potentially substantial undercounts. Emerging Infectious Diseases
Developing One Health Surveillance Systems
Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. The proposed framework can be adapted for putative drivers and surveillance of non-infectious disease threats, e.g., chemical contaminants. One Health
INFECTIOUS DISEASES
Whatever Happened to Zika? (The Problem with Jumping Between Emergencies)
As quickly as it appeared, Zika vanished from global awareness. In 2016, most major news sites largely stopped covering the disease regularly. Despite the absence of a treatment or vaccine, the world’s attention moved on. Zika cases dropped precipitously after 2016, and just a few years later, COVID ravaged the planet, giving us all something new to worry about. But that doesn’t mean Zika is gone. The disease is still out there, infecting people every day. There is still no Zika vaccine, and experts say another large-scale outbreak is likely before too long. In this way, Zika reflects a typical epidemic cycle—an emergent crisis, followed by a brief influx of resources, followed by rich countries’ long and fateful forgetting. The Atlantic
ANTIMICROBIAL RESISTANCE CRISIS
A Novel Antibiotic Class Targeting the Lipopolysaccharide Transporter
Identification and optimization of tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against Carbapenem-resistant Acinetobacter baumannii (CRAB). A clinical candidate derived from the MCP class, zosurabalpin (RG6006), effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models of infection, overcoming existing antibiotic resistance mechanisms. Nature
COVID-19 PANDEMIC
Paxlovid Cuts Covid Death Risk. But Those Who Need It Are Not Taking It.
As Covid rises again, killing about 1,500 Americans each week, medical researchers are trying to understand why so few people are taking Paxlovid, a medicine that is stunningly effective in preventing severe illness and death from the disease. A study of a million high-risk people with Covid found that about 135,000 hospitalizations and 48,000 deaths could have been avoided if half of the patients eligible for the antiviral got it. New York Times
‘Paxlovid Rebound’: Is COVID-19 Rebound Related to COVID-19 Therapy?
Medical rumors die hard, and those surrounding the prevention and treatment of COVID-19 are no exception. However, for individuals who rely on data for decision making, these two studies provide ample evidence in favor of the currently approved drugs for mitigating severe SARS-CoV-2 infection without significantly increasing incidence of rebound, thereby diminishing the likelihood of hospitalization and death. NEJM Journal Watch
Identifying COVID-19 Vaccine Analytics to Prevent Hospitalizations, ED Visits
A large, comprehensive study measured how widespread COVID-19 vaccination needed to be in order to provide protection against serious disease in adults by age groups. “The median number needed to vaccinate to prevent 1 hospitalization was 205 people,” Grannis said. “So if you vaccinate 205 people, you’ll prevent at least 1 hospitalization. The number needed to vaccinate [to prevent] 1 emergency department visit was 156. This is a concrete number that helps providers, helps public health officials, and helps decision makers understand the effectiveness and the volume of vaccines required to have a particular impact.” Contagion Live
Activation-Based Repertoire Analysis for T Cell Clonal Dynamics in Hybrid COVID-19 Immunity
The use of T cell receptor signatures to track activated spike-specific T cell dynamics between recovery from SARS-CoV-2 infection and subsequent mRNA vaccination shows that vaccination effectively recruits pre-existing memory and new CD8+ T cell clonotypes. Nature Immunology
COVID-19 mRNA Vaccine Effectiveness in the Youngest Children
Despite factors that complicate a clear interpretation of these data (e.g., rising rates of natural infection, greater likelihood of vaccine coverage in children with underlying conditions), the most striking information is the overall low rate of vaccine coverage in the youngest age group approved for vaccination. The particularly low rate in non-white children also deserves attention during focused efforts to address vaccine inaccessibility or hesitancy. NEJM Journal Watch
Death Rate of COVID-19 Infection in Different SARS-Cov-2 Variants Related to C-Reactive Protein Gene Polymorphisms
As a result of severe COVID-19, blood cell counts are altered, including an increase in neutrophils and leukocytes, a rise in C-reactive protein (CRP), and a drop in lymphocytes and platelet. The findings of this comprehensive study demonstrate considerable evidence that there are associations between two polymorphisms of the CRP gene with COVID-19 mortality. Scientific Reports
Adapting COVID-19 Contact Tracing Protocols to Accommodate Resource Constraints
Because of constrained personnel time, the Philadelphia Department of Public Health (Philadelphia, PA, USA) adjusted its COVID-19 contact tracing protocol in summer 2021 by prioritizing recent cases and limiting staff time per case. This action reduced required staff hours to prevent each case from 21–30 to 8–11 hours, while maintaining program effectiveness. Emerging Infectious Diseases
Humoral Immune Responses to Monovalent XBB.1.5-Adapted BNT162b2 mRNA Booster in Sweden
Bivalent booster doses delivering both the ancestral and BA.1/BA.5 spike fail to elicit strong omicron-specific humoral immune responses. The global dominance of XBB sublineages prompted the development of further updated monovalent vaccines delivering the XBB.1.5 variant spike. However, a substantially mutated sublineage of BA.2, denoted BA.2.86, has recently emerged and several of its descendants are increasing in frequency. This raises questions whether the XBB.1.5-encoding vaccines will provide adequate protection against this emerging lineage. In this study, monovalent XBB.1.5-adapted booster vaccination substantially enhanced both binding and neutralising antibody responses against a spectrum of variants in an older population with four or more previous vaccine doses. The Lancet Infectious Diseases
Diverse Array of Neutralizing Antibodies Elicited Upon Spike Ferritin Nanoparticle Vaccination in Rhesus Macaques
Here researchers led by the Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research (WRAIR) describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. This study has provided molecular detail of the RBD-specific antibodies that are elicited following SpFN vaccination and explains the previously observed broad neutralizing and protective immune responses. “We are encouraged that neutralizing epitopes targeted by the mAbs isolated in this study overlap with antibody targets elicited in SARS-CoV-2 convalescence, suggesting that SpFN will confer protection beyond animal models.” Nature Communications
ALSO READING
Pathogen Discovery in the Post-COVID Era. Pathogens
Recombination-aware phylogenetic analysis sheds light on the evolutionary origin of SARS-CoV-2. Scientific Reports
Rational Design of a ‘Two-In-One’ Immunogen DAM Drives Potent Immune Response Against Monkeypox Virus. Nature Immunology
Shigella virulence protein VirG is a broadly protective antigen and vaccine candidate. NPJ Vaccines
Swine Disease Reporting System Report #71. Swine Health Information Center
Virological Characteristics of the SARS-Cov-2 JN.1 Variant. The Lancet Infectious Diseases
An mRNA Vaccine Encoding SARS-Cov-2 Receptor-Binding Domain Protects Mice from Omicron Variants. NPJ Vaccines
Impact on the time elapsed since SARS-CoV-2 infection, vaccination history, and number of doses, on protection against reinfection. Scientific Reports
Generation of a Porcine Cell Line Stably Expressing Pig TMPRSS2 for Efficient Isolation of Swine Influenza Virus. Pathogens
Absolute Quantitation of Binding Antibodies From Clinical Samples. NPJ Vaccines