What’s next for mRNA vaccines?
Moderna mRNA vaccines are already in the works to reduce the health risks of latent viruses like Epstein-Barr virus and cytomegalovirus and to tackle additional…
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Robert Langer, ScD, is the David H. Koch Institute professor at MIT and a co-founder of Moderna, the pharmaceutical company behind a COVID-19 mRNA vaccine. In this Q&A, he tells us about the present and future of these versatile vaccines.
Q: The technology behind mRNA vaccines has been available for decades, but it was only with the pandemic that we first saw a publicly available mRNA vaccine. Why didn’t this happen sooner?
RL: While it is true that over the last thirty years hundreds of scientists have worked on developing mRNA vaccines and therapeutics, real breakthroughs in making an effective and commercially viable mRNA vaccine were greatly accelerated by the COVID-19 pandemic. It’s important to realize that Moderna and others like BioNtech and Curevac were in clinical trials for multiple different vaccines and therapeutics at the time the COVID-19 crisis started in late 2019/early 2020.
In fact, Moderna had eight vaccines (including a personalized cancer vaccine, a vaccine against Zika virus, and a dual vaccine against metapneumovirus and a type of parainfluenza) in human clinical trials at that point. Moderna recognized the incredible and unique opportunity to quickly meet the global demand for a COVID-19 vaccine by leveraging our mRNA tools and technologies. All the necessary pieces were in place, such as the correct mRNA chemistry and the development of nanoparticles to protect the messenger RNA (this actually had part of its origins in our MIT lab for which I received the Millennium Technology Prize in 2008). So the organization refocused efforts on bringing a COVID-19 mRNA vaccine to patients as quickly as possible without compromising public safety.
Moderna scientists identified the ideal protein candidate on the coronavirus SARS-CoV-2 virus (the spike protein), determined the mRNA sequence necessary to encode for this protein and, six months later, was given FDA clearance to proceed.
The many advantages of mRNA versus traditional vaccines prompted scientists to use mRNA vaccines to fight SARS-CoV-2. These advantages include the ability to quickly update the vaccine as new variants emerge, the ability to develop combination vaccines to fight several variants (and pathogens) simultaneously, and the ability to rapidly scale to serve a global population.
What’s more, Moderna’s mRNA platform generates antigens with superior biological fidelity and a greater success rate than traditional vaccines—all in record time. mRNA vaccines don’t require a giant manufacturing plant to produce them. All mRNA vaccines and therapeutics can be produced at the same location via the same process.
Q: What are some other diseases or disorders against which mRNA vaccines can provide protection?
RL: Moderna mRNA vaccines are already in the works to reduce the health risks of latent viruses like Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and to tackle additional areas of unmet need, including an all-in-one mRNA vaccine to treat COVID-19, seasonal flu, and respiratory syncytial virus (RSV). Additionally, Moderna plans to develop mRNA vaccines to help patients beat Herpes simplex virus (HSV), MS, cancer, and HIV once and for all.
HSV, CMV, and EBV are large viruses that gain entry into cells via multiple proteins. Identifying which proteins to target remains a challenge, as does the development of adjuvants to fine-tune the body’s immune response. In the case of HIV, the situation is particularly complex.
Simply put, the immune system must be rigorously trained to produce a specific type of antibody (broadly neutralizing antibody or bnAbs), that has been found to be effective at fighting HIV. Further, a truly protective HIV vaccine will likely require a combination of antigens to stimulate the formation of multiple bnAbs classes.
Therefore, mRNA vaccines are limited only by the immune system’s own ability to fight the pathogen. Once an ideal protein candidate is identified, it is a relatively simple process to identify the mRNA needed to encode for those proteins.
Q: Can mRNA vaccines provide universal protection against a family of viruses, such as coronaviruses?
RL: Theoretically, yes. AI, machine learning, and robotic process automation (RPA) are technologies that can help us more rapidly catalog common familial viral elements, predict potential variations and mutations, and identify antigen-protein targets—all while eliminating human error.
Further, these technologies can accelerate the process of identifying the ideal, most productive mRNA sequence needed to generate those proteins. Over time, AI/machine learning refinements will continuously improve the range and effectiveness of this approach by providing ever-larger datasets to draw from.
Q: Do mRNA vaccines have the potential to combat antimicrobial/antibiotic resistance?
RL: Yes. Antimicrobial and antibiotic resistance arises as a natural evolutionary process, the result of genetic variation (“errors”) and mutation in the pathogen, giving rise to novel traits. Organisms that develop traits which make them drug-resistant naturally survive and thrive.
First, mRNA vaccines have the potential to help combat antimicrobial and antibiotic resistance by reducing our reliance on traditional antibiotics. Additionally, Moderna’s mRNA platform helps combat resistance by identifying the most desirable and persistent antigens for targeting, by improving the prediction of new strains, and by accelerating the production of vaccines to defeat those strains.
Finally, by training the immune system to look for specific surface proteins on the bacterium, an mRNA vaccine more effectively targets specific pathogens while avoiding the issue of damaging a patient’s “good” bacteria with increasingly toxic antibiotics. For instance, through the selection of a “coat protein” as the target-antigen, an mRNA vaccine against a drug-resistant strain of malaria has already yielded encouraging results.
Q: On the whole, mRNA vaccines are safer, more efficient, and easier to produce than “traditional” vaccines. However, like with all technologies, there is always room to improve its accessibility, affordability, efficacy, and safety. Cold storage requirements and side effects including possible allergic reactions are some of the issues impacting uptake of these vaccines. Are there any solutions to these (or any other) issues that researchers are currently working upon?
RL: Moderna is leveraging AI and machine learning technologies to identify ways to make mRNA vaccines safer and more durable (with simpler refrigeration requirements) by minimizing the length of mRNA strands. Moderna is implementing a multi-pronged approach to ease the substantial global disease burden by making mRNA vaccines more widely accessible, affordable, efficient, and safe.
Moderna’s mRNA Access program aims to accelerate the creation of new mRNA vaccines through collaboration with global partners. mRNA Access lets outside researchers leverage Moderna’s platform to develop mRNA vaccines against emerging and neglected infectious diseases around the world.
This strategy exponentially expands our brain trust, making the discovery of safer and more efficient vaccines an inevitable outcome. To help ensure the success of our mission to combat the top respiratory diseases worldwide, Moderna has entered into ten-year supply agreements with strategic countries.
Finally, Moderna is expanding its COVID-19 vaccine technology patent-free into 92 additional low- and middle-income countries as well as building an mRNA manufacturing facility in Kenya.
In addition, at MIT, we are working on ways of creating self-boosting vaccines that can be given in a single injection that does not require the patient to return for boosters. We are also developing ways to create more stable nanoparticles, as well as microneedle patches that could be shelf stable and shipped around the world.
Q: Recently, there has been discussion about developing vaccines that can be administered as a pill or a nasal spray. Is this method of delivery possible for mRNA vaccines?
RL: The possibilities for vaccine administration are endless so long as an appropriate, effective delivery mechanism can be found that protects the mRNA from the local environments (e.g., mucus, saliva, stomach acid [HCL]) yet facilitates the delivery of mRNA into the cell. While the gold standard for vaccine administration is through an intramuscular shot in the arm, intranasal COVID-19 vaccines have already been shown to elicit strong cellular immune response in humans.
Additionally, at MIT, Gio Traverso and myself recently developed a self-orienting mRNA “milli-injector” capsule that uses a polymer coating to deliver mRNA to the stomach via milli-needle injections in the gastric lining, thereby avoiding damaging acids. The experiments successfully produced proteins in gastric mucosa, as well as systemic uptake though, due to volume restrictions, their effectiveness may be limited to diseases of the gastrointestinal tract.
A nasal vaccine’s formulation and delivery method must be precisely tuned and would require amplification via immunostimulants. Despite this, several vaccine companies are experimenting with intranasal delivery by tweaking nasal mucosal toxicity, mucoadhesion, and pH. AstraZeneca and the Chalmers University of Technology have initiated mRNA-based nasal spray vaccine development against SARS-CoV-2, where nasal vaccines make the most sense since viral invasion happens via the nasal mucosa.
Advantages of a pill or nasal spray include reduced patient hesitancy and increased compliance. Specific advantages of an intranasal spray include ease of combining vaccines, simple vaccine swapping to accommodate variants, a combined mucosal and systemic immune response, protection at distant mucosal sites, and a faster onset of a strong immune response.
Q: What are some other ways that mRNA vaccine technology can improve human wellbeing that you believe hasn’t yet had enough attention or curiosity?
RL: An mRNA vaccine enables the patient to produce proteins, but these proteins don’t have to be used to stimulate the immune system to fight disease. mRNA vaccine technology can be used to replace missing proteins in patients suffering from inherited metabolic disorders (of which hundreds exist, such as phenylketonuria). These potentially debilitating diseases are caused by an enzyme deficiency; the body is unable to manufacture or break down certain proteins.
Phenylketonuria (PKU) results in low levels of the enzyme phenylalanine hydroxylase, a protein that breaks down phenylalanine. Without it, phenylalanine builds up in the body, often to toxic levels, even causing brain damage. Current treatment is simply the dietary reduction of foods that contain phenylalanine (which includes much more than you think: all meats, milk, eggs, cheese, nuts, soy, beans, and more). The dietary requirements are so severe as to require supplementing with a special drink to ensure the essential nutrients.
Similarly, an mRNA vaccine may be used to potentially help treat depression by enabling patients to boost their levels of serotonin or dopamine to elevate their mood or reduce anxiety. In short, an mRNA vaccine can be used to express any protein and possibly treat almost any disease.
Q: What advice would you give to budding researchers interested in studying and working on mRNA vaccines?
RL: I think it’s important to realize that there are few limits. Whether it’s mRNA vaccines or anything else, I always tell my students to dream big dreams, dreams that can change the world. But if you do that you may run into obstacles. When I first discovered a way to deliver macromolecules including nucleic acids from small particles, I was ridiculed by the scientific community. My first nine research grants were rejected and no engineering department in the world would hire me for a faculty position. But I didn’t give up and I always tell my students to never give up either.
GEN wishes to thank David Olajide, consultant at CURZONPR in London, for providing the raw material for this article.
The post What’s next for mRNA vaccines? appeared first on GEN - Genetic Engineering and Biotechnology News.
depression pandemic coronavirus covid-19 grants vaccine treatment fda clinical trials genetic rna gold
International
Beloved mall retailer files Chapter 7 bankruptcy, will liquidate
The struggling chain has given up the fight and will close hundreds of stores around the world.
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It has been a brutal period for several popular retailers. The fallout from the covid pandemic and a challenging economic environment have pushed numerous chains into bankruptcy with Tuesday Morning, Christmas Tree Shops, and Bed Bath & Beyond all moving from Chapter 11 to Chapter 7 bankruptcy liquidation.
In all three of those cases, the companies faced clear financial pressures that led to inventory problems and vendors demanding faster, or even upfront payment. That creates a sort of inevitability.
Related: Beloved retailer finds life after bankruptcy, new famous owner
When a retailer faces financial pressure it sets off a cycle where vendors become wary of selling them items. That leads to barren shelves and no ability for the chain to sell its way out of its financial problems.
Once that happens bankruptcy generally becomes the only option. Sometimes that means a Chapter 11 filing which gives the company a chance to negotiate with its creditors. In some cases, deals can be worked out where vendors extend longer terms or even forgive some debts, and banks offer an extension of loan terms.
In other cases, new funding can be secured which assuages vendor concerns or the company might be taken over by its vendors. Sometimes, as was the case with David's Bridal, a new owner steps in, adds new money, and makes deals with creditors in order to give the company a new lease on life.
It's rare that a retailer moves directly into Chapter 7 bankruptcy and decides to liquidate without trying to find a new source of funding.
Image source: Getty Images
The Body Shop has bad news for customers
The Body Shop has been in a very public fight for survival. Fears began when the company closed half of its locations in the United Kingdom. That was followed by a bankruptcy-style filing in Canada and an abrupt closure of its U.S. stores on March 4.
"The Canadian subsidiary of the global beauty and cosmetics brand announced it has started restructuring proceedings by filing a Notice of Intention (NOI) to Make a Proposal pursuant to the Bankruptcy and Insolvency Act (Canada). In the same release, the company said that, as of March 1, 2024, The Body Shop US Limited has ceased operations," Chain Store Age reported.
A message on the company's U.S. website shared a simple message that does not appear to be the entire story.
"We're currently undergoing planned maintenance, but don't worry we're due to be back online soon."
That same message is still on the company's website, but a new filing makes it clear that the site is not down for maintenance, it's down for good.
The Body Shop files for Chapter 7 bankruptcy
While the future appeared bleak for The Body Shop, fans of the brand held out hope that a savior would step in. That's not going to be the case.
The Body Shop filed for Chapter 7 bankruptcy in the United States.
"The US arm of the ethical cosmetics group has ceased trading at its 50 outlets. On Saturday (March 9), it filed for Chapter 7 insolvency, under which assets are sold off to clear debts, putting about 400 jobs at risk including those in a distribution center that still holds millions of dollars worth of stock," The Guardian reported.
After its closure in the United States, the survival of the brand remains very much in doubt. About half of the chain's stores in the United Kingdom remain open along with its Australian stores.
The future of those stores remains very much in doubt and the chain has shared that it needs new funding in order for them to continue operating.
The Body Shop did not respond to a request for comment from TheStreet.
bankruptcy pandemic canadaGovernment
Are Voters Recoiling Against Disorder?
Are Voters Recoiling Against Disorder?
Authored by Michael Barone via The Epoch Times (emphasis ours),
The headlines coming out of the Super…
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Authored by Michael Barone via The Epoch Times (emphasis ours),
The headlines coming out of the Super Tuesday primaries have got it right. Barring cataclysmic changes, Donald Trump and Joe Biden will be the Republican and Democratic nominees for president in 2024.
With Nikki Haley’s withdrawal, there will be no more significantly contested primaries or caucuses—the earliest both parties’ races have been over since something like the current primary-dominated system was put in place in 1972.
The primary results have spotlighted some of both nominees’ weaknesses.
Donald Trump lost high-income, high-educated constituencies, including the entire metro area—aka the Swamp. Many but by no means all Haley votes there were cast by Biden Democrats. Mr. Trump can’t afford to lose too many of the others in target states like Pennsylvania and Michigan.
Majorities and large minorities of voters in overwhelmingly Latino counties in Texas’s Rio Grande Valley and some in Houston voted against Joe Biden, and even more against Senate nominee Rep. Colin Allred (D-Texas).
Returns from Hispanic precincts in New Hampshire and Massachusetts show the same thing. Mr. Biden can’t afford to lose too many Latino votes in target states like Arizona and Georgia.
When Mr. Trump rode down that escalator in 2015, commentators assumed he’d repel Latinos. Instead, Latino voters nationally, and especially the closest eyewitnesses of Biden’s open-border policy, have been trending heavily Republican.
High-income liberal Democrats may sport lawn signs proclaiming, “In this house, we believe ... no human is illegal.” The logical consequence of that belief is an open border. But modest-income folks in border counties know that flows of illegal immigrants result in disorder, disease, and crime.
There is plenty of impatience with increased disorder in election returns below the presidential level. Consider Los Angeles County, America’s largest county, with nearly 10 million people, more people than 40 of the 50 states. It voted 71 percent for Mr. Biden in 2020.
Current returns show county District Attorney George Gascon winning only 21 percent of the vote in the nonpartisan primary. He’ll apparently face Republican Nathan Hochman, a critic of his liberal policies, in November.
Gascon, elected after the May 2020 death of counterfeit-passing suspect George Floyd in Minneapolis, is one of many county prosecutors supported by billionaire George Soros. His policies include not charging juveniles as adults, not seeking higher penalties for gang membership or use of firearms, and bringing fewer misdemeanor cases.
The predictable result has been increased car thefts, burglaries, and personal robberies. Some 120 assistant district attorneys have left the office, and there’s a backlog of 10,000 unprosecuted cases.
More than a dozen other Soros-backed and similarly liberal prosecutors have faced strong opposition or have left office.
St. Louis prosecutor Kim Gardner resigned last May amid lawsuits seeking her removal, Milwaukee’s John Chisholm retired in January, and Baltimore’s Marilyn Mosby was defeated in July 2022 and convicted of perjury in September 2023. Last November, Loudoun County, Virginia, voters (62 percent Biden) ousted liberal Buta Biberaj, who declined to prosecute a transgender student for assault, and in June 2022 voters in San Francisco (85 percent Biden) recalled famed radical Chesa Boudin.
Similarly, this Tuesday, voters in San Francisco passed ballot measures strengthening police powers and requiring treatment of drug-addicted welfare recipients.
In retrospect, it appears the Floyd video, appearing after three months of COVID-19 confinement, sparked a frenzied, even crazed reaction, especially among the highly educated and articulate. One fatal incident was seen as proof that America’s “systemic racism” was worse than ever and that police forces should be defunded and perhaps abolished.
2020 was “the year America went crazy,” I wrote in January 2021, a year in which police funding was actually cut by Democrats in New York, Los Angeles, San Francisco, Seattle, and Denver. A year in which young New York Times (NYT) staffers claimed they were endangered by the publication of Sen. Tom Cotton’s (R-Ark.) opinion article advocating calling in military forces if necessary to stop rioting, as had been done in Detroit in 1967 and Los Angeles in 1992. A craven NYT publisher even fired the editorial page editor for running the article.
Evidence of visible and tangible discontent with increasing violence and its consequences—barren and locked shelves in Manhattan chain drugstores, skyrocketing carjackings in Washington, D.C.—is as unmistakable in polls and election results as it is in daily life in large metropolitan areas. Maybe 2024 will turn out to be the year even liberal America stopped acting crazy.
Chaos and disorder work against incumbents, as they did in 1968 when Democrats saw their party’s popular vote fall from 61 percent to 43 percent.
Views expressed in this article are opinions of the author and do not necessarily reflect the views of The Epoch Times or ZeroHedge.
Government
Veterans Affairs Kept COVID-19 Vaccine Mandate In Place Without Evidence
Veterans Affairs Kept COVID-19 Vaccine Mandate In Place Without Evidence
Authored by Zachary Stieber via The Epoch Times (emphasis ours),
The…
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Authored by Zachary Stieber via The Epoch Times (emphasis ours),
The U.S. Department of Veterans Affairs (VA) reviewed no data when deciding in 2023 to keep its COVID-19 vaccine mandate in place.
VA Secretary Denis McDonough said on May 1, 2023, that the end of many other federal mandates “will not impact current policies at the Department of Veterans Affairs.”
He said the mandate was remaining for VA health care personnel “to ensure the safety of veterans and our colleagues.”
Mr. McDonough did not cite any studies or other data. A VA spokesperson declined to provide any data that was reviewed when deciding not to rescind the mandate. The Epoch Times submitted a Freedom of Information Act for “all documents outlining which data was relied upon when establishing the mandate when deciding to keep the mandate in place.”
The agency searched for such data and did not find any.
“The VA does not even attempt to justify its policies with science, because it can’t,” Leslie Manookian, president and founder of the Health Freedom Defense Fund, told The Epoch Times.
“The VA just trusts that the process and cost of challenging its unfounded policies is so onerous, most people are dissuaded from even trying,” she added.
The VA’s mandate remains in place to this day.
The VA’s website claims that vaccines “help protect you from getting severe illness” and “offer good protection against most COVID-19 variants,” pointing in part to observational data from the U.S. Centers for Disease Control and Prevention (CDC) that estimate the vaccines provide poor protection against symptomatic infection and transient shielding against hospitalization.
There have also been increasing concerns among outside scientists about confirmed side effects like heart inflammation—the VA hid a safety signal it detected for the inflammation—and possible side effects such as tinnitus, which shift the benefit-risk calculus.
President Joe Biden imposed a slate of COVID-19 vaccine mandates in 2021. The VA was the first federal agency to implement a mandate.
President Biden rescinded the mandates in May 2023, citing a drop in COVID-19 cases and hospitalizations. His administration maintains the choice to require vaccines was the right one and saved lives.
“Our administration’s vaccination requirements helped ensure the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations,” the White House said.
Some experts said requiring vaccination meant many younger people were forced to get a vaccine despite the risks potentially outweighing the benefits, leaving fewer doses for older adults.
“By mandating the vaccines to younger people and those with natural immunity from having had COVID, older people in the U.S. and other countries did not have access to them, and many people might have died because of that,” Martin Kulldorff, a professor of medicine on leave from Harvard Medical School, told The Epoch Times previously.
The VA was one of just a handful of agencies to keep its mandate in place following the removal of many federal mandates.
“At this time, the vaccine requirement will remain in effect for VA health care personnel, including VA psychologists, pharmacists, social workers, nursing assistants, physical therapists, respiratory therapists, peer specialists, medical support assistants, engineers, housekeepers, and other clinical, administrative, and infrastructure support employees,” Mr. McDonough wrote to VA employees at the time.
“This also includes VA volunteers and contractors. Effectively, this means that any Veterans Health Administration (VHA) employee, volunteer, or contractor who works in VHA facilities, visits VHA facilities, or provides direct care to those we serve will still be subject to the vaccine requirement at this time,” he said. “We continue to monitor and discuss this requirement, and we will provide more information about the vaccination requirements for VA health care employees soon. As always, we will process requests for vaccination exceptions in accordance with applicable laws, regulations, and policies.”
The version of the shots cleared in the fall of 2022, and available through the fall of 2023, did not have any clinical trial data supporting them.
A new version was approved in the fall of 2023 because there were indications that the shots not only offered temporary protection but also that the level of protection was lower than what was observed during earlier stages of the pandemic.
Ms. Manookian, whose group has challenged several of the federal mandates, said that the mandate “illustrates the dangers of the administrative state and how these federal agencies have become a law unto themselves.”
Veterans Affairs Kept COVID-19 Vaccine Mandate In Place Without Evidence
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