News highlights on health security threats and countermeasures curated by Global Biodefense
This week’s selections include Omicron-specific mRNA vaccine trials getting underway; HHS’ designation as High Risk by GAO; introduction of the PREVENT Pandemics Act; Flu forecasting with Inferno; and increased transmissibility of the BA.2 subvariant.
POLICY + INITIATIVES
For the Federal Response to COVID-19, Significant Improvements Needed in Leadership and Oversight
In a new report, GAO designated HHS’s coordination and leadership of public health emergencies as High Risk. This designation is in keeping with long-standing efforts to identify federal programs needing transformation, and to help ensure sustained executive branch and congressional attention so the nation is prepared for future emergencies. For more than a decade, GAO has reported on HHS’s lead role in preparing for and responding to public health emergencies and found persistent deficiencies in HHS’s execution of this role. These deficiencies have hindered the nation’s response to the current COVID-19 pandemic and a variety of past threats, including other infectious diseases—such as the H1N1 influenza pandemic, Zika, and Ebola—and extreme weather events, such as hurricanes. U.S. Government Accountability Office
Next-Generation Biowarfare: Small in Scale, Sensational in Nature?
Biological security threats are moving from the realm of weapons of mass destruction to the domain of information warfare, where small-scale, targeted attacks may still have a massive psychological impact. The COVID-19 pandemic has shown us how effectively fears of infection can close societies, sow mistrust among allies, and create political turmoil. Future biological wars may use the same dynamics to inflict shock and confusion upon the enemy by the mere threat of mass casualties, thereby circumventing several previous limitations of biological warfare. Preparedness must keep pace with these developments, considering not only defense against disinformation but also the need to rapidly mobilize resources at the frontline of molecular biology. Health Security
Options for Article X of the Biological Weapons Convention
This report outlines ten concrete ideas for States Parties to consider in seeking to enhance the implementation of Article X of the Biological Weapons Convention, including: establishing a voluntary funding mechanism to contribute to biorisk reduction activities; foster Biosecurity Diplomacy programs; build biosecurity capacity in low-resource and developing countries; region-specific cooperation plans; and enhance Implementation Support Unit/remedy institutional deficits. UN Institute for Disarmament Research
Murray, Burr Introduce Discussion Draft of Bipartisan Pandemic and Public Health Preparedness and Response Bill
Senator Patty Murray (D-WA), and Ranking Member, Senator Richard Burr (R-NC), released a discussion draft of the Prepare for and Respond to Existing Viruses, Emerging New Threats, and Pandemics Act (PREVENT Pandemics Act), bipartisan legislation focused on strengthening the nation’s public health and medical preparedness and response systems in the wake of the COVID-19 pandemic. U.S. Senate Committee on Health, Education, Labor and Pensions (HELP), STAT
China’s Zero-COVID Strategy: What Happens Next?
In the past few months, China has experienced its largest COVID-19 outbreak since April 2020. Researchers have differing views on when and how China might plan its exit from the zero-COVID strategy. Although the country’s inactivated-virus vaccines have been the most widely used, China has also approved an adenovirus-vector and a protein-subunit vaccine and has trials underway for mRNA candidates. Supplanting the current inactivated-virus vaccine with boosters from other platforms may be key to easing out of the Zero-COVID strategy. Nature
Fresh from the Biotech Pipeline: Too Much, Too Fast?
Looking at 2021’s US Food and Drug Administration (FDA) drug approvals, one might not have known there was still a major health crisis underway. More than 50 new drugs were waved through — close to 2018’s all-time high. The FDA has shown remarkable agility and productivity through the pandemic, but behind the scenes, things were less smooth. The agency has faced staff exhaustion, management upheaval and criticism over lax standards in its accelerated approval pathway. The FDA also lacked a permanent leader for almost the entire year, which some say led to unpredictable decisions. Nature Biotechnology
U.S. Army Begins to Discharge Soldiers Who Refuse COVID-19 Vaccination
As of 26 Jan, 96% of active Army troops have been completely vaccinated, while 3,350 soldiers have refused to get the vaccine. Nearly 5,900 have received temporary exemptions. Soldiers who are discharged for refusing to be vaccinated “will not be eligible for involuntary separation pay” and may have to return any unearned special or incentive pay, the Army said. NPR
‘Dangerous Precedent.’ Ivermectin Could Be Used as COVID Treatment in Indiana Bill
A proposed Indiana bill would allow for ivermectin to be used as a treatment against COVID-19, and health officials warn that if it passes, the consequences could be far-reaching. House Bill 1372 would permit doctors and nurses to “create a standing order” for ivermectin, and pharmacists would be required to dispense the drug, no prescription necessary. The bill would also prohibit the state boards for each profession from taking disciplinary action against any of the medical practitioners involved. Under the bill, information sheets provided with the medication can’t contain any information that might discourage the patient from “using ivermectin for the treatment of COVID-19.” Kansas City Star
White House Issues Planning Guide for Vaccinating Children Under Age 5
The White House today released a preliminary planning guide to inform jurisdictional, federal partner and pharmacy planning to distribute the Pfizer COVID-19 vaccine for children aged 6 months through 4 should the FDA authorize the vaccine for emergency use in this age group. According to the guide, pharmacies may have limited ability to vaccinate these younger children, so encouraging Vaccines for Children providers to enroll as COVID-19 vaccine providers will be critical. American Hospital Association
The $100-billion Toll of a Pig Epidemic in China
Researchers estimate that a 2018 outbreak of African swine fever virus (ASF) led to the loss of at least 38 million more animals than officially acknowledged. Nature (paywall)
MEDICAL COUNTERMEASURES
Gilead COVID Drug Takes Top Spot for U.S. Hospital Spending as Vaccinations Lagged
In 2021 Gilead sold $5.6B of COVID-19 drug remdesivir (average price $2,080 for non-hospitalized patients, $3,120 for hospitalized) and overtook AbbVie’s 20-year-old arthritis drug Humira as the medicine that U.S. hospitals spent the most on. Gilead believes that as the pandemic shifts into an endemic stage and as antiviral pills become more readily available that hospitalizations will decline, limiting the need for Veklury. Still, the company is projecting 2022 sales for the antiviral at $2 billion. Reuters, Fierce Pharma
SARS-CoV-2 Infection and Hospitalization by Vaccination Status, Before and During Omicron Variant Predominance
As of January 8, 2022, during Omicron predominance, COVID-19 incidence and hospitalization rates in Los Angeles County among unvaccinated persons were 3.6 and 23.0 times, respectively, those of fully vaccinated persons with a booster, and 2.0 and 5.3 times, respectively, those among fully vaccinated persons without a booster. During both Delta and Omicron predominance, incidence and hospitalization rates were highest among unvaccinated persons and lowest among vaccinated persons with a booster. CDC Morbidity and Mortality Weekly Report (MMWR)
Pfizer and BioNTech Start Trials of New Omicron-Specific Jab
Pfizer and BioNTech have started clinical trials of a new Covid vaccine which targets the Omicron variant. Pfizer said it expects initial findings from the study, which will enroll 1,420 volunteers, to be available during the first half of 2022. However, it is not exactly clear what data regulators such as those at the FDA would require before authorizing an Omicron-specific vaccine, or what requirements the CDC will have for recommending one. A senior FDA official previously told STAT that the agency hopes to seek global consensus over whether new, variant-specific vaccines are needed and hopes to remain “cautious” and “agile.” BBC News
See also: Moderna Begins Testing Omicron-Matched COVID Shots in Adults AP News
Is the BCG Vaccine an Answer to Future Pandemic Preparedness?
While the development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines was rapid, time to development and implementation challenges remain that may impact the response to future pandemics. Trained immunity via bacille Calmette-Guerin (BCG) vaccination (an antigen agnostic strategy) offers a potential intervention against future novel pathogens via an existing, safe, and widely distributed vaccine to protect vulnerable populations and preserve health system capacity while targeted vaccines are developed and implemented. Vaccines
FDA Fully Approves Moderna COVID Vaccine, Spikevax
After more than a year under Emergency Use Authorization, the U.S. Food and Drug Administration granted full approval on 31 Jan to the mRNA COVID-19 vaccine made by Moderna, which will now be known as Spikevax. In August 2021, FDA granted full approval to the Pfizer/BioNTech mRNA vaccine, known as Comirnaty. CIDRAP, STAT
Early Data Indicate Vaccines Still Protect Against Omicron’s Sister Variant, BA.2
BA.1 is what has driven massive spikes in cases around the world, but in countries including India, the Philippines, South Africa, and several countries in Europe, BA.2 has been picking up proportional steam and demonstrating a growth advantage over BA.1. The two lineages share many mutations but have their own individual genetic twists as well. Thus far, there does not seem to be any loss of vaccine effectiveness against BA.2 compared to BA.1. STAT
Efficacy of an Inactivated Zika Vaccine Against Virus Infection During Pregnancy in Animal Model
A Zika purified inactivated virus (ZPIV) was previously shown to be protective in non-pregnant mice and rhesus macaques. This study further examined the efficacy of ZPIV against Zika virus infection during pregnancy in same animal models. Both single-dose and two-dose (28 days apart) ZPIV vaccination provided approximately 80% efficacy in the prevention of fetal malformations induced by Zika virus infection. The ability of ZIKV to cross the placental and blood-brain barriers to cause severe neurological disorders in developing fetuses makes the development of vaccines an urgent global health priority. NPJ Vaccines
Neutralizing Immunity in Vaccine Breakthrough Infections from the SARS-Cov-2 Omicron and Delta Variants
Researchers found a significantly smaller rise of neutralization titers associated with milder Omicron breakthrough infection in vaccinated individuals, to only approximately one-third of the rise associated with boosting. Results suggest that Omicron-induced immunity may not be sufficient to prevent infection from another, more pathogenic variant, should it emerge in the future. They also highlight the continued importance of vaccine boosters in enhancing immunity, as breakthrough infection alone may not be reliable in eliciting protective titers against re-infection or future infection from different variants. MedRxiv pre-print
BIOSECURITY + BIOPREPAREDNESS
Nipah Virus–Another Pandemic Potential Threat from the World of Zoonotic Viruses
The high mortality characteristic of Nipah virus (NiV) is a factor that can limit the spread of a virus that does not infect another due to the death of the host. However, current NiV outbreaks were usually detected in sparsely populated villages. It can be assumed that in the event of an epidemic in a highly populated place, the increase in infections rate could be much higher, especially since, according to WHO, the incubation period for NiV in extreme cases may last 45 days. Amidst the known and tested strains of NiV so far, differences have been observed in transmission methods, the symptoms type and severity, and finally the size of genomes confirmed by molecular analyses. Indirectly, this indicates the need to include the risk of the emergence of mutations, e.g., facilitating the human-to-human viral transmission. In addition to human-human contact, NiV infection can occur through contact with animals. The primary reservoir of NiV is bats. Frontiers in Microbiology
Pandemic Preparedness: Synthetic Biology and Publicly Funded Biofoundries Can Rapidly Accelerate Response Time
Biofoundries are high-throughput robotic DNA and organism engineering facilities that can generate hundreds or thousands of constructs/strains in just a few days — critical synthetic biology infrastructure which should be available to all nations as a part of their independent bioengineering, biosecurity, and countermeasure response systems. Nature Communications
NBAF Update – Building Scientific Expertise
The U.S. Department of Agriculture’s National Bio and Agro-Defense Facility continues hiring, training in preparation to stand up a national science facility with biosafety level-2, -3 and -4 laboratories in Manhattan, Kansas. NBAF’s workforce development efforts, through a variety of partnerships with USDA Agricultural Research Service (ARS) include longer-term graduate training for those interested in a career in research to prevent foreign animal diseases at several major research universities such as Auburn University, Mississippi State University and Kansas State University. ARS also has partnered with K-State’s Center of Excellence for Emerging and Zoonotic Animal Diseases on a two-week biosafety and transboundary animal diseases summer program for recent bachelor’s and master’s degree graduates. It will provide intensive, hands-on and classroom training at K-State’s Biosecurity Research Institute. The Mercury
An Exploratory Analysis of Infection and Fatality Rates in 177 Countries Associated with Pandemic Preparedness for COVID-19
The findings from this analysis are not surprising but are thoughtfully laid out. The factors that explained the most variation in COVID-19 infection-fatality ratio (IFR) was the age profile of the country, GDP per capita, and national mean BMI. The results also support previous research that has found an association between trust and compliance with public health guidance. The Lancet
Threat, Challenges, and Preparedness for Future Pandemics: A Descriptive Review of Phylogenetic Analysis-Based Predictions
Phylogenomic approaches may further help to facilitate the identification of potential virulent determinants, specifically in the case of emerging viruses, and elucidate evolutionary models of virulence. Infection, Genetics and Evolution
SELECT AGENTS + CBRNE THREATS
The Complexity of Safety in BSL-4 Labs
Every BSL-3 and -4 laboratory operates differently. Each engineering system has different response times, the equipment reacts differently depending on manufacturer, and the architectural fit and finish performs differently in every facility. These subtle differences profoundly affect the control system functionality and necessitate highly flexible and adaptable systems. Lab Manager
Wyoming Biocontainment Facility Now Open
Housed in the back of the Wyoming State Vet Lab (WSVL) in Laramie is the University of Wyoming Biocontainment Facility. The state-of-the-art lab recently received its certification from the CDC as a biosafety level three laboratory (BSL-3) and includes a necropsy suite that can accommodate large animals such as a full-sized bison. “This necropsy suite is designed to help us serve the National Animal Laboratory Health Network. If there was say, an outbreak of Foot and Mouth Disease, we would need a way to get those animals in and test them.” They are planning to focus study on the bacteria that cause wildlife diseases in Wyoming like Q fever, plague, and brucellosis. Wyoming Public Media
Challenges in the Establishment of a Biosafety Testing Laboratory for COVID-19 in Bangladesh
Molecular detection of SARS-CoV-2 must be performed in a BSL-2 laboratory with BSL-3-equivalent infection prevention and control practices. Establishing these facilities within a short timeframe proved to be an enormous challenge, including locating a remote space distant from the university campus to establish a laboratory, motivating the laboratory staff to work with a novel pathogen without any prior experience, allocation of funds for essential equipment and accessories, and arrangement of a safe waste management system for environmental hazard reduction. This report also highlights several limitations, such as the facility’s architectural design that did not follow the biosafety guidelines, lack of continuous flow of funds, and an inadequate number of laboratory personnel. The Journal of Infection in Developing Countries
Bivalent Single Domain Antibody Constructs for Effective Neutralization of Venezuelan Equine Encephalitis
Multiple studies have shown the advantage in using multivalent Single domain antibodies (sdAb) constructs for viral neutralization. Using an immune phage display library derived from a llama immunized with an equine vaccine that included inactivated Venezuelan equine encephalitis virus (VEEV), five sdAb sequence families were identified that showed varying ability to neutralize VEEV. One of the bivalent constructs showed effective neutralization of both VEEV and chikungunya virus. The most potent of the bivalent sdAb constructs inhibited VEEV and prevented the infection of cells at low levels, thus offering the potential to be developed as therapeutics for the treatment of VEEV. Scientific Reports
Transmission Models Indicate Ebola Virus Persistence in Non-Human Primate Populations is Unlikely
Recent serological findings suggest that few non-human primates have antibodies to EVD-causing viruses throughout tropical Africa, suggesting low transmission rates and/or high EVD mortality. Here, stochastic transmission models of EVD in non-human primates assuming high case-fatality probabilities and experimentally observed or field-observed parameters did not allow viral persistence, suggesting that non-human primate populations are highly unlikely to sustain EVD-causing infection for prolonged periods. Journal of the Royal Society Interface
ETEC Heat-Stable Toxin and Ebola Virus Delta Peptide: Similarities and Differences
Enterotoxigenic Escherichia coli (ETEC) STb toxin exhibits striking structural similarity to Ebola virus (EBOV) delta peptide. Both ETEC and EBOV delta peptide are enterotoxins. Comparison of the structural and functional similarities and differences of these two toxins illuminates features that are important in induction of pathogenesis by a bacterial and viral pathogen. Pathogens
Complete Protection Against Yersinia pestis in Mouse Model by Immunization with Inhalable Formulations of rF1-V10 Fusion Protein
Inhalation delivery of vaccines has received increasing attention due to its ability to recruit local immune responses of the bronchopulmonary mucosa in addition to the broader systemic immune response. For more than 70 years, the Y. pestis EV NIIEG strain has been used as a human plague vaccine in the former Soviet Union and confers protection against bubonic and pneumonic plague after administration via inhalation. However, the protection appears to be short-lived, and the vaccine is highly reactogenic, limiting licensing of this vaccine for use in many parts of the world. The preparation of live Y. pestis dry powder is rarely reported in the literature, possibly because of bacterial viability being lost during preparation. Subunit vaccine candidates may thus prove a better option for inhalable powder. Frontiers in Immunology
PUBLIC HEALTH
Side-by-side Comparison of Parent vs. Technician-Collected Respiratory Swabs
Mothers with a range of education levels from low-income communities were able to collect anterior nasal and throat specimens using flocked swabs equally well as technicians. Home-swabbing using dry tubes, and less invasive collection procedures, could enhance respiratory disease surveillance. BMC Public Health
Endemicity Is Meaningless
Even if we could be certain that endemicity was on the horizon, that assuredness does not guarantee the nature of our post-pandemic experience of COVID. There are countless ways for a disease to go endemic. Endemicity says nothing about the total number of infected people in a population at a given time. It says nothing about how bad those infections might get—how much death or disability a microbe might cause. Endemic diseases can be innocuous or severe; endemic diseases can be common or vanishingly rare. Malaria, for example, sickens more than 200 million people a year, and kills at least 400,000, most of them under the age of 5. That, too, is endemicity. The Atlantic
Measles Warning for Children as Jab Rate Falls in England
Coverage for the two doses of MMR that helps protect five-year-olds against measles, mumps and rubella is currently at 85.5%. That is the lowest for a decade, and well below the 95% target recommended to stop a resurgence of measles. BBC News
Official List of Covid-19 Symptoms Must Be Updated
Given that we now know from research such as the ZOE study that the primary symptoms of the omicron variant include runny nose, headache, fatigue, sneezing, and sore throat, it is profoundly unhelpful that the UK government has not updated its official—and now outdated—list of symptoms, which highlights high temperature, a new continuous cough, or a loss or change to sense of smell or taste. The BMJ
Preteens Can Get Vaxxed Without Parent Under California Bill
California would allow children aged 12 and up to be vaccinated without their parents’ consent under a proposal introduced Friday by a state senator who said youngsters “deserve the right to protect themselves” against infectious disease. Currently in California, minors ages 12 to 17 cannot be vaccinated without permission from their parents or guardians, unless the vaccine is specifically to prevent a sexually transmitted disease. AP News
SURVEILLANCE + DETECTION
Fast and Accurate Influenza Forecasting in the U.S. with Inferno
Inferno is a fast and accurate flu forecasting model inspired by Dante, the top performing model in the CDC’s 2018/19 FluSight challenge. Inferno runs in minutes not hours, as other leading forecasting models do. This reduction in runtime constitutes an advancement in flu forecasting, positioning Inferno to scale to more granular geographic units, like counties or health care providers. PLOS Computational Biology
DoD Awards Contract to iHealth Lab for COVID-19 Rapid Antigen Tests in Support of Biden Administration’s 500M Free Home Test Mail-Out
The contract modification on 26 Jan procures an additional 104,166,665 over-the-counter COVID-19 test kits. This effort supports the President’s plan to deliver 500 million free at-home COVID-19 tests to the nation in response to the Omicron variant. The procurement was funded through the American Rescue Plan Act. The transaction brings the total number of kits the DoD has ordered from iHealth Lab at more than 350 million, putting the company at the heart of the government’s effort to boost capacity. Defense.gov, MedTechDive
Study Suggests BA.2 COVID-19 Subvariant More Contagious
A study preprint on how Omicron subvariants transmit in Danish households found that the BA.2 subvariant is substantially more transmissible than the original variant. BA.2 is now dominant in Denmark, with levels rising in other countries, raising questions about how fast current surges will decline. In South Africa, which first reported the original Omicron variant, BA.2 levels are increasing, but against the backdrop of decreasing infections. CIDRAP
HISTORICAL REFLECTIONS
The Great London Plague of 1665 and the US COVID-19 Pandemic Experience Compared
Using Daniel Dafoe’s Journal of the Plague Year, Frank O’Hara examines the experience of the plague, the reactions of people, and changes to social cohesion and compares the current COVID-19 pandemic. These issues get at basic human reactions to crisis, and the similarities and differences between the 17th and 21st centuries are instructive. There were similar behaviors in both centuries regarding hating quarantines, falling for quack remedies, and easing restrictions before the pandemic was over. Maine Policy Review
SPECIAL INTEREST
Alphafold: Highly Accurate Protein Structure Prediction for WHO Priority Pathogens
Alphafold, an AI system that predicts a protein’s 3D structure from its amino acid sequence, has recently added the proteome of nearly all the WHO priority pathogens to their library. DeepMind and EMBL’s European Bioinformatics Institute (EMBL-EBI) have partnered to make these predictions freely available to the scientific community. The database will be expanded during 2022 to cover a substantial proportion of all catalogued proteins. AMR Solutions
DARPA Deputy Returns Home to the UK to Lead a New $1B Government Research Agency
Building off the success of the Defense Advanced Research Projects Agency across the pond, the UK on Tuesday appointed former DARPA deputy Peter Highnam as chief executive of the UK’s new Advanced Research and Invention Agency. UK-born and educated Highnam has spent more than a decade working for the US government, with stints at BARDA, the Intelligence Advanced Research Projects Activity (IARPA), and as director of research at the National Geospatial-Intelligence Agency. Endpoint News