These fridge-free COVID-19 vaccines are grown in plants and bacteria

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - SAN DIEGO

Nanoengineers at the University of California San Diego have developed COVID-19 vaccine candidates that can take the heat. Their key ingredients? Viruses from plants or bacteria.

The new fridge-free COVID-19 vaccines are still in the early stage of development. In mice, the vaccine candidates triggered high production of neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19. If they prove to be safe and effective in people, the vaccines could be a big game changer for global distribution efforts, including those in rural areas or resource-poor communities.

“What’s exciting about our vaccine technology is that is thermally stable, so it could easily reach places where setting up ultra-low temperature freezers, or having trucks drive around with these freezers, is not going to be possible,” said Nicole Steinmetz, a professor of nanoengineering and the director of the Center for Nano-ImmunoEngineering at the UC San Diego Jacobs School of Engineering.

The vaccines are detailed in a paper published Sept. 7 in the Journal of the American Chemical Society.

The researchers created two COVID-19 vaccine candidates. One is made from a plant virus, called cowpea mosaic virus. The other is made from a bacterial virus, or bacteriophage, called Q beta.

Both vaccines were made using similar recipes. The researchers used cowpea plants and E. coli bacteria to grow millions of copies of the plant virus and bacteriophage, respectively, in the form of ball-shaped nanoparticles. The researchers harvested these nanoparticles and then attached a small piece of the SARS-CoV-2 spike protein to the surface. The finished products look like an infectious virus so the immune system can recognize them, but they are not infectious in animals and humans. The small piece of the spike protein attached to the surface is what stimulates the body to generate an immune response against the coronavirus.

The researchers note several advantages of using plant viruses and bacteriophages to make their vaccines. For one, they can be easy and inexpensive to produce at large scales. “Growing plants is relatively easy and involves infrastructure that’s not too sophisticated,” said Steinmetz. “And fermentation using bacteria is already an established process in the biopharmaceutical industry.”

Another big advantage is that the plant virus and bacteriophage nanoparticles are extremely stable at high temperatures. As a result, the vaccines can be stored and shipped without needing to be kept cold. They also can be put through fabrication processes that use heat. The team is using such processes to package their vaccines into polymer implants and microneedle patches. These processes involve mixing the vaccine candidates with polymers and melting them together in an oven at temperatures close to 100 degrees Celsius. Being able to directly mix the plant virus and bacteriophage nanoparticles with the polymers from the start makes it easy and straightforward to create vaccine implants and patches. 

The goal is to give people more options for getting a COVID-19 vaccine and making it more accessible. The implants, which are injected underneath the skin and slowly release vaccine over the course of a month, would only need to be administered once. And the microneedle patches, which can be worn on the arm without pain or discomfort, would allow people to self-administer the vaccine.

“Imagine if vaccine patches could be sent to the mailboxes of our most vulnerable people, rather than having them leave their homes and risk exposure,” said Jon Pokorski, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering, whose team developed the technology to make the implants and microneedle patches.

“If clinics could offer a one-dose implant to those who would have a really hard time making it out for their second shot, that would offer protection for more of the population and we could have a better chance at stemming transmission,” added Pokorski, who is also a founding faculty member of the university’s Institute for Materials Discovery and Design.

In tests, the team’s COVID-19 vaccine candidates were administered to mice either via implants, microneedle patches, or as a series of two shots. All three methods produced high levels of neutralizing antibodies in the blood against SARS-CoV-2.

Potential pan-coronavirus vaccine

These same antibodies also neutralized against the SARS virus, the researchers found.

It all comes down to the piece of the coronavirus spike protein that is attached to the surface of the nanoparticles. One of these pieces that Steinmetz’s team chose, called an epitope, is almost identical between SARS-CoV-2 and the original SARS virus.

“The fact that neutralization is so profound with an epitope that’s so well conserved among another deadly coronavirus is remarkable,” said co-author Matthew Shin, a nanoengineering Ph.D. student in Steinmetz’s lab. “This gives us hope for a potential pan-coronavirus vaccine that could offer protection against future pandemics.”

Another advantage of this particular epitope is that it is not affected by any of the SARS-CoV-2 mutations that have so far been reported. That’s because this epitope comes from a region of the spike protein that does not directly bind to cells. This is different from the epitopes in the currently administered COVID-19 vaccines, which come from the spike protein’s binding region. This is a region where a lot of the mutations have occurred. And some of these mutations have made the virus more contagious.

Epitopes from a nonbinding region are less likely to undergo these mutations, explained Oscar Ortega-Rivera, a postdoctoral researcher in Steinmetz’s lab and the study’s first author. “Based on our sequence analyses, the epitope that we chose is highly conserved amongst the SARS-CoV-2 variants.”

This means that the new COVID-19 vaccines could potentially be effective against the variants of concern, said Ortega-Rivera, and tests are currently underway to see what effect they have against the Delta variant, for example.

Plug and play vaccine

Another thing that gets Steinmetz really excited about this vaccine technology is the versatility it offers to make new vaccines. “Even if this technology does not make an impact for COVID-19, it can be quickly adapted for the next threat, the next virus X,” said Steinmetz.

Making these vaccines, she says, is “plug and play:” grow plant virus or bacteriophage nanoparticles from plants or bacteria, respectively, then attach a piece of the target virus, pathogen, or biomarker to the surface.

“We use the same nanoparticles, the same polymers, the same equipment, and the same chemistry to put everything together. The only variable really is the antigen that we stick to the surface,” said Steinmetz.

The resulting vaccines do not need to be kept cold. They can be packaged into implants or microneedle patches. Or, they can be directly administered in the traditional way via shots.

Steinmetz and Pokorski’s labs have used this recipe in previous studies to make vaccine candidates for diseases like HPV and cholesterol. And now they’ve shown that it works for making COVID-19 vaccine candidates as well.

Next steps

The vaccines still have a long way to go before they make it into clinical trials. Moving forward, the team will test if the vaccines protect against infection from COVID-19, as well as its variants and other deadly coronaviruses, in vivo.

###

Paper: “Trivalent subunit vaccine candidates for COVID-19 and their delivery devices.” Co-authors include Angela Chen, Veronique Beiss, Miguel A. Moreno-Gonzalez, Miguel A. Lopez-Ramirez, Maria Reynoso and Joseph Wang, UC San Diego; Hong Wang and Brett L. Hurst, Utah State University.

This work was funded in part by a National Science Foundation both through a RAPID grant (CMMI-2027668) and through the UC San Diego Materials Research Science and Engineering Center (MRSEC, grant DMR-2011924).

Disclosure: Nicole Steinmetz and Jon Pokorski are co-founders of and have a financial interest in Mosaic ImmunoEngineering Inc. All other authors declare no competing interests.

---

JOURNAL

Journal of the American Chemical Society

DOI

10.1021/jacs.1c06600 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Trivalent subunit vaccine candidates for COVID-19 and their delivery devices

ARTICLE PUBLICATION DATE

7-Sep-2021

COI STATEMENT

Nicole Steinmetz and Jon Pokorski are co-founders of and have a financial interest in Mosaic ImmunoEngineering Inc. All other authors declare no competing interests.

Officials leading hurricane response need ‘risk literacy’

Higher numeracy led to better evacuation decisions, study finds

Peer-Reviewed Publication

OHIO STATE UNIVERSITY

COLUMBUS, Ohio – When a hurricane is bearing down on a coastal city, emergency management officials are tasked with making life-and-death choices: Do they mandate that people leave the area? Which communities should evacuate, and when?

 

New research suggests that emergency management officials often do not have the numeracy skills needed to make the best decisions based on data they receive about which residents to evacuate during a hurricane and when to make the decision.

 

The study, published online Aug. 30 in the Bulletin of the American Meteorological Society, showed that the most numerate officials were almost twice as likely as less numerate ones to provide additional evacuation times to their coastal communities. Less numerate ones, on the other hand, gave their communities less advance warning, and when they finally did issue evacuations, over-evacuated tens of thousands more people.

 

And, the study found, federal agencies need to supply emergency management officials with the most complete information available in order for them to make the best choices for people who live in a disaster’s path.

 

This is not to say emergency management officials are not good at math, said Noah Dormady, lead author of the study and an associate professor of public policy at The Ohio State University.

 

“It’s more they haven’t received the right training in probability and risk to effectively understand scientific forecasts that contain probability information,” Dormady said.

 

The study was based on a pair of experiments designed to study and evaluate officials’ decision-making during a natural disaster. The study is among the first to evaluate evacuation decision-making by emergency management officials, rather than by individuals deciding whether or not to leave an area because of a storm.  

 

The study involved 81 emergency managers and other public safety officials predominantly from coastal states that are affected by hurricanes, as well as 227 Ohio State graduate and upper-division students from related fields of study. The researchers began their experiments by testing each subject’s ability to make decisions using probability and statistics – a sort of baseline math test that allowed them to evaluate each participant’s numeracy.  In other words, how well they understood the ways probability and statistics might play out in the real world.

 

Researchers then provided the study participants with a scenario based on a real storm – Hurricane Rita in 2005.  Rita was among the strongest hurricanes ever recorded in the Gulf of Mexico, hitting land near the Louisiana-Texas border, killing 120 people and causing an estimated $18.5 billion in damages. Participants were not told the scenario was based on Rita, so they could not use any knowledge of the storm to guide their decisions.

 

Participants were randomly assigned to treatments with varying amounts of information about the approaching storm. Some subjects received a great deal of information, including the forecasted track and potential alternative tracks; others received limited information.

 

The researchers asked study participants to determine whether to evacuate, when to evacuate and whom to evacuate. Decisions were structured to coincide with the release of advisories from the National Hurricane Center (NHC).

 

Basing the experiments on a real disaster allowed researchers to determine which choices were “good.” Because the outcome was known to the researchers, they could evaluate the areas affected – those that either under-evacuated or over-evacuated regions.

 

The researchers found that people who scored well on the baseline math test made better choices on behalf of the community. People with higher numeracy issued evacuation orders that gave people more time to leave the storm’s path. People who have the practical ability to evaluate and understand risk ordered evacuations in the simulated disaster about nine hours earlier than people who did not have that skillset, the study found.

 

“This tells us that public trust in evacuation orders, which has been waning for years, could be improved if the population had greater confidence in their emergency management leaders’ ability to make sound decisions when they are given probabilistic forecasts,” Dormady said. “People need to trust that their neighborhood is not being over-evacuated out of an abundance of caution simply because public officials didn’t understand the risk.”

 

The study also found that officials who had the most complete set of forecast data were more likely to issue evacuation orders earlier, giving people in the hurricane’s path more time to get out of town than they would have had otherwise. That additional time was significant, the study found, adding between 16.6 and 22.8 hours to a community’s evacuation time.

 

Those hours, Dormady said, could be the difference between life and death for people in a storm’s path, and could also make evacuations, which are often a safety risk themselves, more safe. In fact, in some major disasters, more people die from poorly administered evacuations than from the catastrophic event itself.

 

“Extra hours are crucial – they give people more time to pack and prepare, they give emergency management officials more time to communicate the importance of evacuating, and they make evacuations, overall, more safe,” said Dormady, “And what we saw is that more complete forecast information gave emergency management officials the tools they needed to make better choices for their communities.”  

 

Co-authors of this study include Anthony Fasano, Drew Flanagan and William Welch at Ohio State, Alfredo Roa-Henriquez at Johns Hopkins University, and Dylan Wood at the University of Notre Dame.

 

This work was funded by the National Science Foundation.

 

 

#

 

 

CONTACT: Noah Dormady, dormady.1@osu.edu

 

Written by Laura Arenschield, arenschield.2@osu.edu

---

JOURNAL

Bulletin of the American Meteorological Society

DOI

10.1175/BAMS-D-21-0008.1 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Informational Determinants of Large-area Hurricane Evacuations

ARTICLE PUBLICATION DATE

30-Aug-2021

 

Neanderthal genes tell us about how old our ancestors were when they had children

Peer-Reviewed Publication

AARHUS UNIVERSITY

 

IMAGE: ARCHAIC SEQUENCE LENGTH DECAY (BLACK BANDS ON CHROMOSOMES) FOR DIFFERENT POPULATIONS SAMPLED AT MULTIPLE TIME POINTS. THE LENGTH OF GENERATION INTERVALS (GI) IS REPRESENTED BY THE COLOR GRADIENT ON THE TREE (YELLOW : LONG GI; MAROON : SHORT GI). view more 

CREDIT: MOISÈS COLL MACIÀ, AARHUS UNIVERSITY

A new study suggests that generation intervals have fluctuated during the past 40,000 years of human evolution in contrast to what has been commonly assumed. The results indicate that human life history can change appreciably in response to external and cultural factors

The authors from Aarhus University in Denmark and the Max Planck Institute for Evolutionary Anthropology in Germany used Neanderthal fragments scattered in non-African genomes as molecular clocks to estimate generation intervals in Eurasian and American populations.

“This new way of using genomic data enabled us to retrieve information about our human life traits buried in the past, which complements what can be learned from archaeology about our history,” says Professor Mikkel Heide Schierup, leader of the project.

The research team report in Nature Communications on 7. September, that humans in populations in Europe reproduced on average at a younger age than populations from east Eurasia and America over the past 40,000 years.

“We estimate a difference of 3 to 5 years between the mean generation interval among populations. We believe that this difference was probably more dramatic. If the change happened during the last 10,000 years for example, we are probably diluting the signal over the 40,000 years period we study,” says PhD student Moisès Coll Macià, first author of the study.

The results obtained about generation intervals are reflected in the accumulation of genetic changes in different parts of the world.

“Older parents transmit different mutations than younger ones to their children. In this study, we find that populations estimated to have older parents from their Neanderthal legacy also have mutations suggesting older parenthood” says Coll Macià.

These mutational differences also allowed the researchers to tease apart whether changes in generation interval is due to changes in the fathers’ age at reproduction, the mothers’ age at reproduction or both.

“For instance, we see that east Asian populations tended to have older fathers than mothers, while European populations had similar ages for both,” says Coll Marcià”.

So why did the lengths of generations differ historically around the world?

The authors speculate that this was probably a response to changes in the environment. Differences in climate, but also technological and cultural developments in human societies, might have made living conditions more or less favorable to reproduce and thus played an important role in deciding which was the best time to have descendants.

“In the future, we will be able to use the wealth of ancient and modern human genome sequences appearing at a fast rate to make a fine map of changes to age of human reproduction, that we can relate to environmental and cultural conditions,” professor Schierup suggests.

---

JOURNAL

Nature Communications

DOI

10.1038/s41467-021-25524-4 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Different historical generation intervals in human populations inferred from Neanderthal fragment lengths and mutation signatures

ARTICLE PUBLICATION DATE

7-Sep-2021

 

How can we overcome negotiation impasses? New research from ESMT Berlin explores effective solutions

Peer-Reviewed Publication

ESMT BERLIN

Martin Schweinsberg, assistant professor of organizational behavior at ESMT Berlin and a leading expert in negotiations, together with professor Stefan Thau from INSEAD and professor Madan M. Pillutla from London Business School, examined the impact of impasses in negotiations research. Much of the research on negotiations ignores impasses – situations in which one or two parties discontinue the negotiation, because one or both parties prefer no agreement, or because they could not reach an agreement even if they would have benefitted from the agreement.  

Professor Schweinsberg says, “Many business activities entail negotiations, whether it’s defining a deadline, convincing a stakeholder to support a new strategy, or deciding on a business acquisition. Research shows that leaders spend around 15% to 26% of their working hours negotiating – and many of these negotiations end without an agreement. Understanding why negotiations end with an impasse can help leaders become more effective, improve business outcomes, and make employees happier.” 

The researchers reviewed and systematically coded more than 1,000 research papers on negotiations to understand what we know about why negotiations end without an agreement. Three specific types of negotiation impasses emerged from this careful analysis, and each impasse type requires specific solutions to be resolved. 

Wanted impasse 

Wanted impasses occur when both parties desire an impasse, potentially caused by egocentric biases, time pressure, impoverished communication channels, or simply because they have more attractive alternatives. Wanted impasses can be resolved by negotiating on the levels of interest not positions, accelerating negotiation processes, and offering symbolic concessions. 

Forced impasse 

Forced impasses occur when one party seeks an impasse against the will of the other party and can be caused by interpersonal factors including extreme first offers, dominance, and anger expressions. Forced impasses are resolved by taking the other party’s perspective, swapping lead negotiators, and eventually mediation or arbitration.  

Unwanted impasse 

Unwanted impasses occur when neither party seeks an impasse, and the negotiation still ends without an agreement. Unwanted impasses can be caused by high levels of informational complexity, distorted framing of the negotiation, or by agents. Unwanted impasses can be resolved by framing the negotiation so that both parties recognize the negotiation’s win-win potential, by reducing the agent fees, or by simplifying complex information. 

The negotiation experts suggest that academic research on negotiation impasses is rare partially because negotiation exercises assume that a deal will take place and ignore impasses how to deal with negotiations that end without an agreement. 

“In classroom and laboratory situations, impasses are rare,” says Professor Schweinsberg. “Their prevalence in the real world (around 29% of negotiations, according to our survey) is not mirrored in the negotiation literature. Leaders need to be effective when negotiations are deadlocked and negotiation scholars should help leaders with that.” 

The findings can help management scholars understand the mechanism underlying challenges across all kinds of negotiations, whether they are at the personal, professional, or organizational level.  

###

This research was published open access in the Journal of Management and can be read for free here: https://negotiationimpasses.com/paper/. 

---

JOURNAL

Journal of Management

DOI

10.1177/01492063211021657 

 

NSF grant means first of it's kind laser system coming to US

University of Central Florida will be home to multi-user high-peak-power, high-repetition-rate ultrafast infrared laser system.

Grant and Award Announcement

UNIVERSITY OF CENTRAL FLORIDA

 

IMAGE: LI FANG LEADS THE TEAM THAT WILL SET UP THE LASER, WHICH WILL BE THE BACKBONE OF A MULTI-USER FACILITY FOR ATTOSECOND SOFT X-RAYS AND TERAHERTZ (UFAST). THIS FACILITY ONCE COMPLETE WILL BE ONE OF A KIND IN THE WORLD AND IS EXPECTED TO ENHANCE U.S. COMPETITIVENESS IN HIGH-FLUX ULTRAFAST TECHNOLOGIES AND ATTOSECOND SCIENCE. view more 

CREDIT: UNIVERSITY OF CENTRAL FLORIDA

The U.S. National Science Foundation has awarded UCF a grant to purchase and install an almost $2 million high-peak-power, high-repetition-rate ultrafast infrared laser system — a first of its kind in the world.

The money is an investment in the cutting-edge research being conducted at UCF, which is advancing knowledge and technologies in physical, chemical, and planetary sciences, as well as optical engineering. 

The laser will be the backbone of a multi-User Facility for Attosecond Soft x-rays and Terahertz (UFAST). This facility once complete will be one of a kind in the world and is expected to enhance U.S. competitiveness in high-flux ultrafast technologies and attosecond science.

“UFAST will provide unique and versatile tools for in-depth scientific investigations and will advance knowledge in multiple research fields that may lead to applications, such as low-cost and efficient solar panels, light-frequency electronics, new laser cutting technology, and plasma synthesis, as well as extend our understanding of our solar system,” says Li Fang, project lead and an assistant professor of physics. Fang was recently awarded a Department of Energy Career Award for her cutting edge work.

The physics field that will be advanced by UFAST studies and documents processes that occur on the timescale of attoseconds, which is one billionth of a billionth of a second. The ability to make measurements with attosecond precision allows researchers to study the fast motion of electrons inside atoms, and molecules, and solid materials at their natural time scale. Measuring this fast motion can help researchers understand fundamental aspects of how light interacts with matter, which can inform efforts to harvest solar energy for power generation, detect chemical and biological weapons, perform medical diagnostics, and more.

UCF already has a reputation in attosecond science. 

In 2012 a team from UCF created the world’s shortest laser pulse — a 67-attosecond pulse of extreme ultraviolet light — and in the process gave scientists a new tool to watch quantum mechanics in action. In 2017, the same team beat its own record with a 53- attosecond pulse. It was another breakthrough work at UCF’s Institute for the Frontier of Attosecond Science and Technology (iFAST).

The NSF funding comes from its Major Research Instrumentation program, which was created to support the acquisition or development of a multi-user research instruments. According to the NSF the MRI program provides support to acquire critical research instrumentation without which advances in fundamental science and engineering research may not otherwise occur.

 The grant will enable transformational scientific investigations, attract talented students to UCF and attosecond science, and improve the diversity of our future workforce, Fang says. 

“In addition to the multidisciplinary nature of its applications, the facility will be accessible to users across the U.S. and from around the globe and will stimulate collaborations across research fields and institutions, as well as between experimentalists and theorists,” she says.  

UFAST will not only advance science, but it will give UCF graduate and undergraduate students and postdoctoral scholars access to pioneering ultrafast research and technologies not easily accessible anywhere else.

This new high-power laser will drive the world’s fastest tabletop soft x-ray source of unprecedented power, as well as other highly sought-after light sources in the long-wavelength and terahertz range. These advanced light sources will enable several advanced detection technologies. 

“The new infrared laser is unique,” says CREOL and physics Professor Zenghu Chang, a co-principal investigator. “This new laser infrastructure and the light sources it enables at UFAST will strengthen UCF’s excellence in laser technology and bring excellent opportunities to the attosecond science community.”

The rest of the grant team includes: CREOL professors Konstantin Vodopyanov and M.J. Soileau; associate professors of Physics Michael Chini, Madhab Neupane, and Adrienne Dove; assistant professors of Physics Mihai Vaida, Chris Bennet, and Kerri Donaldson Hanna; and CREOL assistant professor Xiaoming Yu. 

 

Apologizing to customers after product failures can encourage repurchase, stave off lawsuits

Peer-Reviewed Publication

BINGHAMTON UNIVERSITY

BINGHAMTON, N.Y. -- Companies that express remorse in the wake of a product failure are more likely to encourage customers to repurchase from them, according to new research from Binghamton University, State University of New York.

The study, which examines how emotional reactions affect how consumers interact with a company, also found that remorseful statements can help stave off retaliatory actions such as lawsuits.

“Human beings are emotional. When something bad occurs, the first thing that happens is an emotional reaction – usually anger. We wanted to find out how the buyer’s anger translates into action when a product failure is caused by the seller’s negligence,” said Subimal Chatterjee, SUNY distinguished teaching professor of marketing at Binghamton University’s School of Management.

Chatterjee and his fellow researchers conducted two experiments to determine how consumers react to product failures, and looked specifically at two groups of consumers – a “promotion-focused” group, who were naturally inclined to gain something positive from the buyer-seller relationship, and a “prevention-focused” group, who sought to avoid failure in the buyer-seller relationship. 

In one experiment, participants were shown an apology from a CEO, while participants in the other experiment were shown a message from a lawyer looking to seek damages from the company.

The researchers found that consumers were more likely to repurchase from the company when there was a match between the framing of the CEO apology and their natural inclinations, meaning a promotion-framed message worked best with promotion-focused consumers, and a prevention-framed message worked best with prevention-focused consumers. 

Researchers also found that when consumers had an option to join a class action suit, the framing of the lawyer’s message had more of an impact on the prevention-focused consumers than the promotion-focused consumers.  

“There is a lesson here,” said Chatterjee. “Framing a message can only go so far in persuading consumers, and it appears to work less when they are angry.”

According to Chatterjee, the most effective apologies encourage forgiveness and stress that consumers have more to gain from reengagement with the company rather than retaliation.

“By framing your apology with a promotion message, you’re acknowledging the failure, but telling the consumer that there is more to gain from trying again,” he said.

While Chatterjee’s study focuses on the framing of messages to consumers, he stressed that other factors, such as consumer perceptions of authenticity, are important.

“Consumers are smart. They can figure out if messages are authentic or inauthentic,” he said. “One good way to show that you are authentic is to highlight your corporate social responsibility footprint. That goes a long way in strengthening your apology, or conversely, blunting calls to punish you,” he said.

The study, “To forgive or retaliate? How regulatory fit affects emotional reactions and repurchase decisions following product failures,” has been published in the Journal of Consumer Marketing, and was co-authored by Gizem Atav and Rajat Roy.

---

JOURNAL

Journal of Consumer Marketing

DOI

10.1108/JCM-05-2020-3843 

SUBJECT OF RESEARCH

People

ARTICLE TITLE

To forgive or retaliate? How regulatory fit affects emotional reactions and repurchase decisions following product failures

ARTICLE PUBLICATION DATE

15-Jun-2021

 

History of traumatic brain injury linked to higher rates of prescription opioid use and misuse

Evidence bolsters 'Perfect Storm' of opioid risks after TBI, reports special issue of JHTR

Peer-Reviewed Publication

WOLTERS KLUWER HEALTH

September 7, 2021 – Adults with a history of traumatic brain injury (TBI), even years previously, are at increased risk of use and misuse of prescription opioid medications, reports a study in the September/October special issue of the Journal of Head Trauma Rehabilitation (JHTR). The official journal of the Brain Injury Association of America, JHTR  is published in the Lippincott portfolio by Wolters Kluwer.

After adjustment for other factors, "[P]ersons with TBI compared to those without had over 52 percent increased risk for using prescription opioids in the past year, and over 65 percent increased risk for prescription opioid misuse," according to the report by Rachel Sayko Adams, PhD, MPH, of Brandeis University, Waltham, Mass. The JHTR special issue presents eight invited research papers providing evidence for the hypothesis linking a history of TBI to a unique pattern of increased vulnerability to pain and other interrelated risks for opioid use and its potential consequences, including overdose.

New data support 'Perfect Storm' hypothesis of opioid risks after TBI

The study included data on nearly 3,500 participants from a 2018 study of health risks among adults in Ohio. Overall 22.8 percent of participants said they had at least one TBI sometime in their lives. Of these individuals, more than two-thirds had had a TBI with loss of consciousness, most before age 20.

One-fourth of participants (25.5 percent) reported using a prescription opioid in the past year. About three percent met criteria for prescription opioid misuse – defined as using opioids more frequently or in higher doses than prescribed and/or using a prescription opioid not prescribed to the respondent. (The study did not address use of illicit opioids, such as heroin, following TBI – a gap in knowledge requiring further research.)

Participants with a history of TBI were more likely to report prescription opioid use in the past year: 30.9 percent, compared to 23.9 percent of those without a TBI history. After controlling for demographic factors (sex, age, race/ethnicity, and marital status), history of TBI was associated with a 52 percent increase in the odds of prescription opioid use and a 65 percent increase in the odds of prescription opioid misuse.

The findings support the hypothesis – outlined by Dr. Adams and other TBI researchers, in a paper published last year – that  persons with a history of TBI face a three-phase "Perfect Storm" of increased opioid risks:

• Phase I: Greater exposure to opioids related to pain and other factors following TBI
• Phase II: Greater likelihood of progression to long-term opioid treatment, opioid misuse, or diagnosed opioid use disorder (OUD)
• Phase III: Greater barriers to successful treatment for patients with TBI who develop OUD.

These "cascading vulnerabilities" may combine to lead to potential consequences of opioid misuse and OUD, including increased risk for overdose and suicide.

The special issue papers add to the growing body of evidence that persons with a history of TBI are more likely to be treated with prescription opioids (Phase I), in both civilian and military settings. Some papers provide new evidence that a history of TBI is associated with increased odds of opioid misuse (Phase II), in adolescents as well as adults. So far, there have been few studies investigating if TBI leads to increased obstacles to OUD treatment (Phase III).

Persons with TBI are at increased risk for pain, which is thought to be an important driver of their increased opioid risks. One of the new studies finds that opioids are more likely to be prescribed for patients with comorbid pain and/or psychological health conditions after TBI. Previous research has found that alcohol or drug use is a risk factor for TBI, and persons with TBI are at elevated risk for substance use after injury. The new studies in the special issue suggest that prescription opioid use follows a similar cyclical pattern with TBI as alcohol or other drugs.

"Empirical investigation into each element of the 'perfect storm' is needed to identify treatment targets and prevention opportunities," Dr. Adams writes in an introduction to the special issue. She and her colleagues believe that substance use treatment providers need to be trained to screen for and address problems related to a history of TBI, while rehabilitation professionals treating TBI patients should perform screening for at-risk substance use.

Click here to read “Association of Lifetime History of Traumatic Brain Injury With Prescription Opioid Use and Misuse Among Adults”

DOI: 10.1097/HTR.0000000000000729

###

About The Journal of Head Trauma Rehabilitation

The Journal of Head Trauma Rehabilitation is a leading, peer-reviewed resource that provides up-to-date information on the clinical management and rehabilitation of persons with traumatic brain injuries. Six issues each year aspire to the vision of “knowledge informing care” and include a wide range of articles, topical issues, commentaries and special features. It is the official journal of the Brain Injury Association of America.

About the Brain Injury Association of America

The Brain Injury Association of America is the country’s oldest and largest nationwide brain injury advocacy organization. Our mission is to advance awareness, research, treatment and education and to improve the quality of life for all individuals impacted by brain injury. Through advocacy, we bring help, hope and healing to millions of individuals living with brain injury, their families and the professionals who serve them. 

About Wolters Kluwer

Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the clinicians, nurses, accountants, lawyers, and tax, finance, audit, risk, compliance, and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with advanced technology and services.

Wolters Kluwer reported 2020 annual revenues of €4.6 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 19,200 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands.

Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students in effective decision-making and outcomes across healthcare. We support clinical effectiveness, learning and research, clinical surveillance and compliance, as well as data solutions. For more information about our solutions, visit https://www.wolterskluwer.com/en/health and follow us on LinkedIn and Twitter @WKHealth.

For more information, visit www.wolterskluwer.com, follow us on Twitter, Facebook, LinkedIn, and YouTube.

---

JOURNAL

Journal of Head Trauma Rehabilitation

DOI

10.1097/HTR.0000000000000729 

First-in-human clinical trial for a vaccine to treat opioid use disorders enrolls first patients

The vaccine has been developed by researchers at the University of Minnesota Medical School

Business Announcement

UNIVERSITY OF MINNESOTA MEDICAL SCHOOL

MINNEAPOLIS/ST. PAUL (09/07/2021) — The first patients have been enrolled in a phase 1 randomized placebo-controlled clinical trial to study a therapeutic vaccine for opioid use disorder developed by researchers at the University of Minnesota Medical School.

Funded by a grant from the National Institutes of Health, the trial will test the safety and potential efficacy of a vaccine that is designed to selectively prevent the euphoric and toxic effects of oxycodone. 

Volunteers for the trial are being enrolled at Columbia University in New York City and Clinilabs Drug Development Corporation, based in Eatontown, New Jersey.

Marco Pravetoni, PhD, a leading expert of biologics for the treatment of substance use disorders and developer of the vaccine candidate, is an associate professor of pharmacology and medicine at the University of Minnesota Medical School. His laboratory led the development of a series of vaccines and monoclonal antibodies effective in counteracting respiratory depression (depressed breathing) and bradycardia (depressed heart rate) induced by oxycodone, fentanyl and heroin in preclinical studies, as published in the Journal of Pharmacology and Experimental Therapeutics and the Journal of Medicinal Chemistry.

The vaccine currently being tested stimulates the body’s immune system to produce antibodies to oxycodone. If someone who has been vaccinated takes oxycodone, those antibodies would bind to the drug molecule, stopping it from entering the brain and, ultimately, preventing the “high” produced by the drug. Because of its selectivity for oxycodone, the vaccine will not interfere with FDA-approved medications, including methadone, buprenorphine, naltrexone and naloxone, potentially offering a long-lasting, safe and cost-effective alternative that is complementary to standard medical intervention for opioid use disorders. 

“In this study, my laboratory will conduct pharmacokinetic and immunological monitoring in blood samples from immunized volunteers to ensure that they are making antibodies to oxycodone and determine whether or not the antibodies are preventing the drug from reaching the brain,” said Pravetoni, who is also a member of the U of M Medical School’s Medical Discovery Team on Addiction.

Sandra Comer, PhD, director of the Opioid Laboratory in the Division on Substance Use Disorders in the Department of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons, is the principal investigator of the study. Comer will oversee a team of physicians and nurses led by Jeanne Manubay, MD, the study’s medical director, who is monitoring the patients’ response to the vaccine, including their subsequent drug use and behaviors. She has nearly three decades of experience in developing medications for treating opioid and other substance use disorders and provides overall scientific and regulatory oversight of the clinical trial.

“This medication approach is unique in that it can be used alone or in combination with other treatment medications and, importantly, may offer patients long-lasting protection against overdose if they relapse to opioid use,” Comer said. “The long-term goal of this program is to develop a series of opioid vaccines that target other commonly used opioids, such as heroin and fentanyl. We are very excited about this research and hope to eventually provide a safe, new treatment option for patients with opioid use disorder.”

The study seeks volunteers who:

• Are between the ages of 18-59;

• Are currently using opioids and not seeking treatment for drug use; and,

• Have prior experience with intranasal opioid use.

The study plans to enroll up to 45 volunteers. Volunteers will be closely monitored for several weeks on inpatient units at Columbia University Irving Medical Center and at Clinilabs to look for adverse events and determine their response to oxycodone after vaccination, before studying their drug behavior on an outpatient basis.

“Clinilabs is privileged to be working with the University of Minnesota Medical School and Columbia University on this groundbreaking trial. Exploring a preventative vaccine to treat opioid use disorder has the potential to be life-altering for patients and their families who are battling opioid abuse,” said Gary Zammit, Clinilabs’ President and CEO.

To learn more about the study or to review the volunteer qualifications, call 646-774-6243 or visit https://recruit.cumc.columbia.edu/clinical_trial/2168. 

###

Research reported in this press release was supported by The National Institute on Drug Abuse of the National Institutes of Health under award number UG3DA047711. The total project cost is financed with federal dollars. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu. 

Photos and videos from the Pravetoni Lab are available for media use. Credit should be given to Lisa Anderson, University of Minnesota Medical School.

---

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People