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Tripledemic Rouses Vaccine Developers and Variant Trackers

Some things that come in threes are seen in a positive light. But threes also have their dark side, as evidenced by the so-called tripledemic—the unprecedented…



Some things that come in threes are seen in a positive light: the Triple Crown of horse racing, the Three Musketeers, and hockey’s “hat trick.” But threes also have their dark side, as evidenced by the so-called tripledemic—the unprecedented concurrence this winter of three major respiratory viruses: respiratory syncytial virus (RSV), seasonal influenza, and COVID-19. At times, the tripledemic has threatened to overwhelm the healthcare system.

By early winter, RSV, flu, and COVID-19 were surging more or less simultaneously. Might such multipronged attacks become the norm? “Most certainly COVID-19 is not going away,” says Steven J. Lawrence, MD, professor of medicine, Division of Infectious Diseases, Washington University School of Medicine. “However, many believe that once the variants settle down, there will be a more seasonal pattern. The problem is that when a new variant appears, it begins to infect a lot of people no matter what time of year it is. However, we do see some seasonality with COVID-19.”

Lawrence also suggests that the tripledemic pattern may be here to stay: “It is likely that this is going to be the new normal with each year seeing the co-circulation and seasonality of RSV, flu, and COVID-19.”

Surveillance and testing

Identifying which virus is causing an infection is not only critical to appropriate medical management, but also necessary for properly tracking outbreaks. A global network has already been established for tracking influenza. “There are reference sites that have been around a long time, such as doctors’ offices and clinics,” Lawrence notes. “Each year, members send their flu isolates into a central repository for analysis. Thus, we are tracking not only flu numbers but also strains and the mutations that are occurring.” An updated weekly U.S. influenza surveillance report (FluView) is available from the Centers for Disease Control and Prevention (CDC).

Influenza A and B viruses cause seasonal epidemics of flu disease almost every winter in the United States, but only influenza A viruses are known to cause global epidemics. Both A and B viruses receive special attention from the CDC, which supplied this image of an A virus. The week this article went to press, the CDC reported that of the A viruses known to be circulating, 72% were A(H3N2) and 28% were A(H1N1). H: hemagglutinin; N; neuraminidase; M2: matrix-2 protein; RNP: ribonucleoprotein.

Lawrence indicates that COVID-19 surveillance lags behind but is becoming more robust in tracking numbers of cases and in using sophisticated genomic analyses of SARS-CoV-2 to identify which variants are circulating. He points out, “However, RSV hasn’t caught up in surveillance with the others. There are pockets around the country performing RSV surveillance. They don’t have quite the robustness that has been established for flu and COVID-19, but they still provide insights.”

As for testing to diagnose viruses, PCR testing remains the gold standard for identifying and differentiating each virus. “During flu season, multiplex tests performed by healthcare providers are valuable to distinguish each virus,” Lawrence elaborates. “While home COVID-19 tests are widely available, they are not as available for other viruses. But since there is overlap among symptoms, and since there are specific treatments for COVID-19 and flu, it is important to determine which virus is causing infections.”

According to Lawrence, there are two major forms of therapy for COVID-19. The first form involves the administration of drugs that stop viral replication. These drugs include Paxlovid (nirmatrelvir/ritonavir), Veklury (remdesivir), and Lagevrio (molnupiravir). The second form involves monoclonal antibodies such as Evusheld (tixagevimab/cilgavimab).

For pre-exposure prophylaxis, Evusheld is becoming less effective against the newer COVID-19 variants. Bebtelovimab, another monoclonal antibody, no longer works against the current dominant strain (Omicron variant BQ1.1). Accordingly, the Food and Drug Administration has pulled bebtelovimab’s emergency use authorization.

Lawrence stresses that it is important for patients to seek flu treatment, especially if they are high-risk individuals. The CDC reports that all viruses evaluated were susceptible to the influenza antivirals Tamiflu (oseltamivir), Rapivab (peramivir), Relenza (zanamivir), and Xofluza (baloxavir).

Faster and more potent flu vaccines

Keeping up with fast-mutating viruses is no easy feat. For example, the rapid emergence of a veritable smorgasbord of SARS-CoV-2 variants has challenged vaccine developers. Fortunately, these developers have been able to take advantage of mRNA technology, which continues to improve and expedite the appearance of COVID-19 vaccines. And now mRNA technology is being used to engineer improved flu vaccines.

Scientists at the Washington School of Medicine are conducting a Phase II study to assess a new mRNA flu vaccine developed by Moderna (mRNA-1010). “Our study is designed to examine in detail the immunologic response of this mRNA vaccine as compared to the standard flu vaccine,” reports Rachel Presti, MD, PhD, associate professor of medicine and medical director of the institution’s Infectious Diseases Clinical Research Unit.

According to Presti, one major challenge of the current flu vaccines is that they sometimes target the wrong strains. “Every year, the CDC has data for how well the flu vaccine strains chosen matched the strains that actually circulated,” she notes. “Because traditional flu vaccines take longer to prepare, we have to choose strains very early in the year. Even when the best available data is used, incorrect strains are sometimes chosen to be in the vaccine.

“What is exciting about mRNA vaccines is that the speed of preparing them allows us to wait, for example, until late summer to see what is circulating in the world. Those few extra months provide better current data to select more accurately the best strains to use.”

Although the technology to produce mRNA vaccines is still new, Presti feels that it could be the wave of the future, especially against viruses. “For viruses where we know what antigens we need to target, it may be of more use,” she points out. “For bacterial pathogens that may require targeting of sugar structures, for example, mRNA vaccines may not be the solution. But I do think more and more mRNA vaccines will be developed—especially against epidemic-like viruses, where we need to respond rapidly.”

RSV immunity gap?

One reason RSV has surged this year may relate to an “immunity gap,” according to Dan Rocca, PhD, a research leader at Charles River Laboratories. “During the pandemic, the safety measures such as lockdowns, mask wearing, and social distancing which kept us protected from catching COVID-19 also protected us from the large variety of other respiratory viruses such as influenza and RSV,” he says. “It is likely that many of these preventative COVID-19 measures led to a lack of exposure to the virus and an ‘immunity gap’ where the usual immune response to existing RSV strains that populations build over time was subsequently greatly diminished.”

Several therapies are being used to help the most susceptible or most at-risk patients avoid hospitalization. “Palivizumab [sold under the brand name Synagis], for example, is a monoclonal antibody therapy directed specifically at RSV,” details Sandy Kimber, PhD, group leader of the Portishead UK Infection Team at Charles River. “Ribavirin [sold under brand names such as Moderiba, Virazole, and Ribasphere] is another antiviral inhibitor therapy that is effective against RSV, but it isn’t used in children due to long-term safety concerns.

“More RSV antiviral inhibitors that prevent viral entry and replication are in development, as well as therapeutic antibodies to limit infection. One such example is the recently approved nersivemab from AstraZeneca/Sanofi [sold under the brand name Beyfortus]—a long-lived monoclonal antibody of demonstrated superiority that has cost benefits over current acute therapies.”

RSV maternal vaccine

Although the development of vaccines against RSV has lagged behind the development of vaccines against flu and COVID-19, a new maternal vaccine candidate against RSV is undergoing clinical trials. One of the scientists working on these trials is Carol Kao, MD, assistant professor of pediatrics, Washington University School of Medicine.

respiratory syncytial virus (RSV)
The surveillance of respiratory syncytial virus (RSV) is not as robust as the surveillance of influenza and COVID-19. At present, this surveillance gap is a source of consternation. RSV is surging, possibly because of an “immunity gap,” a population-level vulnerability that may be due to anti-COVID-19 safety measures reducing exposure to RSV. (This image shows RSV under a fluorescence microscope.)

“RSV is the number one cause of infant hospitalizations in the United States,” she says. “Worldwide, it causes over 30 million infections in children less than five years of age and is a leading cause of death in infants. RSV prevention in infants is a huge unmet need; there are no widely available preventative measures or treatments for RSV illness. All we can really do is support babies with intravenous fluids or supplemental oxygen until they get better.”

She adds, however, that the new RSV vaccine candidate looks promising. “This would be the first RSV vaccine approved,” she remarks. “So, this is a very exciting time.”

The new vaccine candidate is called RSVpreF, and it is being developed by Pfizer. The company says that RSVpreF is a bivalent vaccine candidate that is composed of equal amounts of recombinant RSV prefusion F from subgroups A and B.

“Given that young infants are the most severely affected by RSV, a maternal vaccine given during pregnancy would allow for infants to be protected right off the bat, during their most vulnerable early months of life,” Kao explains. “This is similar to why we give influenza, COVID-19, and Tdap (pertussis) vaccines to women during pregnancy.”

Kerstin Pohl
Kerstin Pohl, SCIEX

Pfizer recently announced positive top-line data from MATISSE (MATernal Immunization Study for Safety and Efficacy), a Phase III, randomized, double-blinded, placebo-controlled trial that started in June 2020 and that has spanned multiple RSV seasons in both the northern and southern hemispheres. Pregnant women were vaccinated in their late second to third trimester of pregnancy, followed for six months after delivery, and their infants were followed for at least one to two years. Kao reports, “Preliminary study results, which included 7,400 pregnant people and infants, showed that the vaccine was well tolerated and 82% effective at preventing severe lower respiratory tract infections in babies for the first three months of life and 70% effective for the first six months of life.”

Advancing analytics and surveillance

Even amid the tripledemic, scientists continue to improve the analysis of vaccines as well as the surveillance of viral variants. For example, scientists at Sciex and Precision NanoSystems are collaborating to develop highly analytical tests to support the development of mRNA vaccines and other products.


Adam Crowe
Adam Crowe, PhD
Precision NanoSystems

“The established and ideal carriers for mRNA-based medicines, including certain COVID-19 vaccines and mRNA therapeutics, are lipid nanoparticles (LNPs),” asserts Kerstin Pohl, senior manager of cell and gene therapy and nucleic acids, SCIEX. Recent studies, however, have identified an impurity that originates from ionizable lipids, a key component of LNPs. “Ionizable lipids are susceptible to chemical alterations—predominantly oxidation,” Pohl notes. “Site-specific oxidation can lead to the formation of reactive lipid species that bind to mRNA to form mRNA-lipid adducts. These adducts, even in tiny amounts, can prevent mRNA-triggered protein expression, reducing drug efficacy.”

Ramin Khaksa

Sciex has developed a new electron-activated dissociation (EAD) mass spectrometry approach that can analyze LNPs and lipid raw materials at very low abundance, revealing exact oxidation sites. According to Adam Crowe, PhD, manager of analytical development, Precision NanoSystems, advanced analytics can help biopharmaceutical companies manage the challenges of mRNA lipidation. He adds that these companies are increasingly requiring support from contract development and manufacturing organizations.

“Direct monitoring of adduct formation on mRNA via ion-pair reversed-phase high-performance liquid chromatography with ultraviolet spectroscopy detection and mass spectrometry has proven effective,” Crowe states. “However, significant expertise is required to optimize methods, generate controls, and ensure assay robustness.”

electron-activated dissociation (EAD)
Besides improving the surveillance of virus variants, scientists are improving the analysis of vaccines. The latter activity is aided by the use of electron-activated dissociation (EAD) mass spectrometers such as the ZenoTOF 7600, an instrument developed by SCIEX. By enabling the tunable fragmentation of all molecule types, the ZenoTOF can detect and quantify impurities such as ionizable lipids, which may originate from the lipid nanoparticles that carry mRNA-based vaccines and medicines.

Improvements in next-generation sequencing are also tightening the surveillance of variants. Ramin Khaksar, PhD, COO and CSO at Clear Labs, says that such improvements are evident in his company’s surveillance solution: “It is a uniquely complete end-to-end, near-real-time solution that integrates software, hardware, bioinformatics, analytics, and reporting with a single touch point. This integrated solution enables NGS applications to be more adaptable to a variety of laboratories without barriers from lab and computer infrastructure or access to skilled scientists and bioinformaticians.”

The tally

At the end of 2022, the CDC released estimates that it had gathered for the flu season up to that point: 20 million illnesses, 210,000 hospitalizations, and 13,000 deaths. The good news was that the CDC also indicated that the majority of flu viruses tested were antigenically similar to those included in the current year’s vaccine. At the time, 44% of U.S. counties were experiencing medium to high COVID-19 levels in each community. (To see current results, visit the CDC’s COVID Data Tracker, an online resource.)

Although experts warn that the tripledemic trend will likely continue in subsequent seasons, scientists continue fighting back by developing improved antiviral vaccines and treatments as well as more sophisticated and accurate analytical and surveillance technologies.


The post Tripledemic Rouses Vaccine Developers and Variant Trackers appeared first on GEN - Genetic Engineering and Biotechnology News.

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As We Sell Off Our Strategic Oil Reserves, Ponder This

As We Sell Off Our Strategic Oil Reserves, Ponder This

Authored by Bruce Wilds via Advancing Time blog,

One of Biden’s answers to combating…



As We Sell Off Our Strategic Oil Reserves, Ponder This

Authored by Bruce Wilds via Advancing Time blog,

One of Biden's answers to combating higher gas prices has been to tap into America's oil reserves. While I was never a fan of the U.S. Strategic Petroleum Reserve (SPR) program, it does have a place in our toolbox of weapons. We can use the reserve to keep the country running if outside oil supplies are cut off. Still, considering how out of touch with reality Washington has become, we can only imagine the insane types of services it would deem essential next time an oil shortage occurs.

Sadly, some of these reserves found their way into the export market and ended up in China. We now have proof that the President's son Hunter had a Chinese Communist Party member as his assistant while dealing with the Chinese. Apparently, he played a role in the shipping of American natural gas to China in 2017. It seems the Biden family was promising business associates that they would be rewarded once Biden became president. Biden's actions could be viewed as those of a traitor or at least disqualify him from being President.

The following information was contained in a letter from House Oversight Committee ranking member James Comer, R-Ky. to Treasury Secretary Janet Yellen dated Sept. 20. 

"The President has not only misled the American public about his past foreign business transactions, but he also failed to disclose that he played a critical role in arranging a business deal to sell American natural resources to the Chinese while planning to run for President.”

Joe Biden, Comer said, was a business partner in the arrangement and had office space to work on the deal, and a firm he managed received millions from his Chinese partners ahead of the anticipated venture. While part of what Comer stated had previously been reported in the news, the letter, cited whistleblower testimonies, as well as emails, a corporate PowerPoint presentation, and a screenshot of encrypted messages. These as well as  bank documents that committee Republicans obtained suggest Biden’s knowledge and involvement in the plan dated back to at least 2017.

The big point here is;

  • The Strategic Petroleum Reserve, which was established in 1975 due to the 1973 oil embargo, is now at its lowest level since December 1983.

In December 1975, with memories of gas lines fresh on the minds of Americans following the 1973 OPEC oil embargo, Congress established the Strategic Petroleum Reserve (SPR). It was designed “to reduce the impact of severe energy supply interruptions.” What are the implications of depleting the SPR and is it still important?

The U.S. government began to fill the reserve and it hit its high point in 2010 at around 726.6 million barrels. Since December 1984, this is the first time the level has been lower than 450 million barrels. Draining the SPR has been a powerful tool for the administration in its effort to tame the price of gasoline. It also signaled a "new era" of intervention on the part of the White House. 

This brings front-and-center questions concerning the motivation of those behind this action. One of the implications of Biden's war on high oil prices is that it has short-circuited the fossil investment/supply development process.  Capital expenditures among the five largest oil and gas companies have fallen as the price of oil has come under fire. The current under-investment in this sector is one of the reasons oil prices are likely to take a big jump in a few years. Production from existing wells is expected to rapidly fall.

The Supply Of Oil Is Far More Constant And Inelastic Than Demand

It is important to remember when it comes to oil, the supply is far more constant and inelastic than the demand. This means that it takes time and investment to bring new wells online while demand can rapidly change. This happened during the pandemic when countries locked down and told their populations and told them to stay at home. This resulted in the price of oil temporarily going negative because there was nowhere to store it.

Draining oil from the strategic reserve is a short-sighted and dangerous choice that will impact America's energy security at times of global uncertainty. In an effort to halt inflationary forces, Biden released a huge amount of crude oil from the SPR to artificially suppress fuel prices ahead of the midterm elections. 

To date, Biden has dumped more SPR on the market than all previous presidents combined reducing the reserves to levels not seen since the early 1980s. In spite of how I feel about the inefficiencies of this program, it does serve a vital role. It is difficult to underestimate the importance of a country's ability to rapidly increase its domestic flow of oil. This defensive action protects its economy and adds to its resilience. 

Biden's actions have put the whole country at risk. Critics of his policy pointed out the Strategic Petroleum Reserve was designed for use in an emergency not as a tool to manipulate elections. Another one of Biden's goals may be to bring about higher oil prices to reduce its use and accelerate the use of high-cost green energy.

Either way, Biden's war on oil has not made America's energy policies more efficient or the country stronger.

Tyler Durden Sat, 03/25/2023 - 18:30

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The Disinformation-Industrial Complex Vs Domestic Terror

The Disinformation-Industrial Complex Vs Domestic Terror

Authored by Ben Weingarten via,

Combating disinformation…



The Disinformation-Industrial Complex Vs Domestic Terror

Authored by Ben Weingarten via,

Combating disinformation has been elevated to a national security imperative under the Biden administration, as codified in its first-of-its-kind National Strategy for Countering Domestic Terrorism, published in June 2021.  

That document calls for confronting long-term contributors to domestic terrorism.

In connection therewith, it cites as a key priority “addressing the extreme polarization, fueled by a crisis of disinformation and misinformation often channeled through social media platforms, which can tear Americans apart and lead some to violence.” 

Media literacy specifically is seen as integral to this effort. The strategy adds that: “the Department of Homeland Security and others are either currently funding and implementing or planning evidence–based digital programming, including enhancing media literacy and critical thinking skills, as a mechanism for strengthening user resilience to disinformation and misinformation online for domestic audiences.” 

Previously, the Senate Intelligence Committee suggested, in its report on “Russian Active Measures Campaigns and Interference in the 2016 Election” that a “public initiative—propelled by Federal funding but led in large part by state and local education institutions—focused on building media literacy from an early age would help build long-term resilience to foreign manipulation of our democracy.” 

In June 2022, Democrat Senator Amy Klobuchar introduced the Digital Citizenship and Media Literacy Act, which – citing the Senate Intelligence Committee’s report – would fund a media literacy grant program for state and local education agencies, among other entities. 

NAMLE and Media Literacy Now, both recipients of State Department largesse, endorsed the bill. 

Acknowledging explicitly the link between this federal counter-disinformation push, and the media literacy education push, Media Literacy Now wrote in its latest annual report that ... 

... the federal government is paying greater attention to the national security consequences of media illiteracy.

The Department of Homeland Security is offering grants to organizations to improve media literacy education in communities across the country. Meanwhile, the Department of Defense is incorporating media literacy into standard troop training, and the State Department is funding media literacy efforts abroad.

These trends are important for advocates to be aware of as potential sources of funding as well as for supporting arguments around integrating media literacy into K-12 classrooms. 

When presented with notable examples of narratives corporate media promoted around Trump-Russia collusion, and COVID-19, to justify this counter-disinformation campaign, Media Literacy Now president Erin McNeill said: “These examples are disappointing.”

The antidote, in her view is, “media literacy education because it helps people not only recognize the bias in their news sources and seek out other sources, but also to demand and support better-quality journalism.” (Emphasis McNeill’s)

Tyler Durden Sat, 03/25/2023 - 17:30

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Disney World Event Gives Florida Gov. DeSantis the Middle Finger

Walt Disney’s CEO Bob Iger has shown no willingness to back down in the face of the governor’s efforts to campaign against diversity training.



Walt Disney's CEO Bob Iger has shown no willingness to back down in the face of the governor's efforts to campaign against diversity training.

Florida Gov. Ron DeSantis has made Disney World, one of his state's largest employers, the target of his so-called war on woke. 

At the root of the dispute are former Walt Disney (DIS) - Get Free Report CEO Bob Chapek's remarks opposing the Republican governor's new law, which limits the ability of educators to discuss gender identity and sexual orientation with children.

Labeled the Don't Say Gay bill, the law met with huge pushback from Disney employees, who had criticized Chapek for initially not speaking out against the bill.

That led the then-Disney boss to take a direct stand against the governor's actions, which in turn led DeSantis to strip the company of its special tax status.  

DON'T MISS: Huge Crowds Force Disney World to Make Big Changes

DeSantis has decided to use Disney as the center of his political-theater culture war because it's an easy, and nonmoving, target. The company can't pack up Disney World and move it to New York, Massachusetts, or some other liberal bastion, so it mostly has to take whatever the governor dishes out.

But while DeSantis wants to use Disney as a target, he's mostly playing to the cameras; clearly, he's not actually looking to take down the largest single-site employer in the U.S. Disney World generates tens of thousands of jobs, pays the state a lot of money. and brings in billions of tourism dollars -- many of which are spent outside its gates in the broader Florida economy.

Image source: Shutterstock/TheStreet Illustration

Disney CEO Iger Uses Actions, Not Words

Disney CEO Bob Iger understands that actions speak louder than words and words can come back to haunt you.

The returned Mouse House boss has not called out DeSantis, nor did he fight the governor's takeover of its Reedy Creek Improvement District.

On paper, Disney World appears to have lost its right to self-govern. That's true, but it doesn't mean much because it's not as if the state -- even DeSantis's handpicked cronies who now oversee the former Reedy Creek Improvement District -- intend to actually get in Disney's way. The company prints money for the state.

So, that's why Iger -- who had publicly spoken against the Don't Say Gay bill when he was a private citizen and not Disney CEO, has not called out DeSantis. A speech decrying the governor's actions, pointing out that they “put vulnerable, young LGBTQ people in jeopardy,” as he said before taking the CEO job back, would not help Disney.

Instead, Iger has let his company's actions speak. 

Disney World plans to host a "major conference promoting lesbian, gay, bisexual and transgender rights in the workplace" at the Disney World Resort this September, the Tampa Bay Times reported.

Disney Boldly Challenges DeSantis

Disney World will host the annual Out & Equal Workplace Summit in September.

"The largest LGBTQ+ conference in the world, with more than 5,000 attendees every year. It brings together executives, ERG leaders and members, and HR and DEI professionals and experts -- all working for LGBTQ+ equality," the event's organizer, Out & Equal, said on its website. 

"Over more than 20 years, Summit has grown to become the preferred place to network and share strategies that create inclusive workplaces, where everyone belongs and where LGBTQ+ employees can be out and thrive." 

The Tampa Bay Times called simply hosting the event "a defiant display of the limits of DeSantis’s campaign against diversity training."

Disney World has hosted the event previously and the company has a relationship with Out & Equal going back many years.

Instead of giving a speech and becoming even more of a right-wing-media talking point, Iger showed his employees where Disney stands through his actions. It's a smart choice by a seasoned executive not to become an actor in DeSantis's political theater.

The Florida governor wants to be perceived as battling 'woke" Disney without actually hurting his state's relationship with the company. The newspaper described exactly how that works when it looked at the new government powers the state has taken from the theme park giant.

The subsequent legislation left most of Disney’s special powers in place despite the governor’s attempt to dissolve the district. The conservative members the governor appointed to the board hinted at the first meeting of the new board that they would exercise leverage over Disney, such as prohibiting COVID-19 restrictions at Disney World. But legal experts have said that the new board’s authority has no control over Disney content.

DeSantis wants a culture war, or at least one that'll play out in the media. Iger knows better and has played the situation perfectly.   


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