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Nanoparticle-based COVID-19 vaccine could target future infectious diseases

Just one dose of a new nanoparticle-based COVID-19 vaccine was enough to produce an immune response in animals on track with vaccines currently in clinical…

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Just one dose of a new nanoparticle-based COVID-19 vaccine was enough to produce an immune response in animals on track with vaccines currently in clinical use. And with minor changes, Northwestern University researchers hope the same vaccine platform could target other infectious diseases.

Credit: Credit image to Mirkin lab / Northwestern University

Just one dose of a new nanoparticle-based COVID-19 vaccine was enough to produce an immune response in animals on track with vaccines currently in clinical use. And with minor changes, Northwestern University researchers hope the same vaccine platform could target other infectious diseases.

In a new study, 100% of mice who received the protein-based immunization survived when challenged with lethal doses of the SARS-CoV-2 virus, which causes COVID-19. None of the mice experienced lung damage due to SARS-CoV-2 exposure. All mice who did not receive this nanoparticle vaccine died in a 14-day trial.

The results, published this week in the Proceedings of the National Academy of Sciences, outline the structure-function relationships between the first spherical nucleic acid (SNA) vaccine developed to protect against viral infections.

“What makes this vaccine different than other vaccines is the approach we take to design them,” said Dr. Michelle Teplensky, co-first author of the paper. “Even as recently as a few years ago people focused on selecting the right target to train the immune system and the right stimulant to activate it, not on how those components were arranged structurally and presented to the body.”

Called SNAs, the nanoparticles that house the immune target are a form of globular DNA that can enter and stimulate immune cells with extreme efficiency. SNAs have been tested in more than 60 cell types. Researchers experimentally determined the ideal ratio between the SNA’s shell and core density that produces the most potent response.

SNA vaccines have been used to treat mice with triple negative breast cancer — and more vaccines for other cancers are in development.

Chad A. Mirkin, the inventor of SNAs and the paper’s corresponding author, led the study and said the platform can translate to infectious diseases.

“This is a remarkable demonstration of rational vaccinology — the idea that the structure of a vaccine, as opposed to just components, can have a profound influence on efficacy,” Mirkin said. “While we have previously shown this to be the case for cancer immunotherapies, this is the first demonstration for an infectious disease.”

Mirkin is the George B. Rathmann Professor of Chemistry in Northwestern’s Weinberg College of Arts and Sciences, director of the International Institute of Nanotechnology and member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Making the drug

Vaccines typically take years to develop. But with COVID-19 came astonishing advancements in this arena. Mirkin challenged Teplensky, a postdoctoral fellow in Mirkin’s lab, to work with Ph.D. student and co-first author Max Distler, to evaluate whether the SNA platform could be used to create a potent vaccine, and expand its scope of impact. The two finished the project in just nine months — roughly the same amount of time as commercial developers.

Typical viral immunizations consist of a mixture of molecules from the virus (called antigens) that tell the immune system what its target will be (the virus), and other molecules (called adjuvants) stimulate the immune system to boost the body’s ability to tackle that target when it appears later. Because the mixture isn’t traditionally packaged together, researchers predict that cells within patients are not getting a potent dose of both antigens and adjuvants.

That’s where structure comes into play. Mirkin coined the term “rational vaccinology” to describe how co-delivery and timing of these two drugs via one nanoparticle can make vaccines more effective. Tiny changes at the nanoscale can have big implications for a vaccine’s efficacy and predictability.

Mirkin’s team packaged the antigen (a portion from COVID-19’s infamous spike protein) inside the core of an SNA, and used a specific sequence of DNA known to stimulate the immune system (adjuvant) as the radial shell surrounding the core. The researchers injected mice under the skin, causing an immune response to the spike protein, and then monitored antibody production in the weeks following injection.

Challenging the results

Two weeks following the injection, mice vaccinated with the SNA vaccine had the highest antibody production compared to those vaccinated with a simple saline mixture of the same components, even outperforming other formulations containing commercially used adjuvants (which have been used in formulations of shingles, Hepatitis B and flu vaccinations) by 14-fold.

Antibodies correlate to protection against infection, establishing the platform’s potential in the COVID-19 and infectious disease space. Protein-based vaccines also have fewer side effects and can be stored at normal refrigerator temperature, lowering production and distribution costs considerably.

The researchers looked at papers from commercially available COVID-19 vaccinations and found other studies’ final antibody production at two weeks was “right on track” with their own.

Just to be sure, the team sent their vaccine off to Argonne National Laboratory and allowed them to be put to the test by vaccinating mice and then infecting them with high doses of the SARS-CoV-2 virus in a double-blind study. One hundred percent of mice dosed with the SNA vaccine survived through the end of the trial with no lung damage caused by COVID-19 pneumonia.

Stopping future viruses

Using COVID-19 as a case study to compare how well the vaccine worked was mainly practical. But it also calls attention to the broader implications of the SNA as an infectious disease platform.  

Teplensky says that COVID-19 caused a shift in behavior toward infectious diseases. “People didn’t recognize and appreciate the emergent power that infectious disease can have,” Teplensky said. “We saw an opportunity to use COVID as a case study to shed light on the shortcomings in the vaccination space.”

Distler said, “with this case study, although the results are quite impressive, the goal was not to compete with existing COVID vaccines. We’re preparing for the next mutation, or the next disease in need of a highly structured vaccine because eventually there will be another emergent disease.” According to the researchers, the platform could even be used to target something as complex as HIV.

“The modularity of this approach implies that a quick tweak might only be required to make a new vaccine for a future virus, especially if what we’ve observed previously with the cancer vaccine works,” Mirkin said. “All we’d need to do is change what we’re teaching the immune system to target.”

The paper, “Spherical Nucleic Acids as an Infectious Disease Vaccine Platform,” came together as a collaboration between Northwestern scientists, physicians, and engineers, the Argonne National Laboratory and University of Chicago. The research was supported by the Air Force Office of Scientific Research (award FA9550-17-1-0348), the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital and the National Cancer Institute of the National Institutes of Health (under awards R01CA208783 and P50CA221747).


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Government

CDC Announces Overhaul After Botching Pandemic

CDC Announces Overhaul After Botching Pandemic

After more than two years of missteps and backpedaling over Covid-19 guidance that had a profound…

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CDC Announces Overhaul After Botching Pandemic

After more than two years of missteps and backpedaling over Covid-19 guidance that had a profound effect on Americans' lives, the Centers for Disease Control (CDC) announced on Wednesday that the agency would undergo a complete overhaul - and will revamp everything from its operations to its culture after failing to meet expectations during the pandemic, Bloomberg reports.

Director Rochelle Walensky began telling CDC’s staff Wednesday that the changes are aimed at replacing the agency’s insular, academic culture with one that’s quicker to respond to emergencies. That will mean more rapidly turning research into health recommendations, working better with other parts of government and improving how the CDC communicates with the public. -Bloomberg

"For 75 years, CDC and public health have been preparing for Covid-19, and in our big moment, our performance did not reliably meet expectations," said Director Rochelle Walensky. "I want us all to do better and it starts with CDC leading the way.  My goal is a new, public health action-oriented culture at CDC that emphasizes accountability, collaboration, communication and timeliness."

As Bloomberg further notes, The agency has been faulted for an inadequate testing and surveillance program, for not collecting important data on how the virus was spreading and how vaccines were performing, for being too under the influence of the White House during the Trump administration and for repeated challenges communicating to a politically divided and sometimes skeptical public."

A few examples:

Walensky made the announcement in a Wednesday morning video message to CDC staff, where she said that the US has 'significant work to do' in order to improve the country's public health defenses.

"Prior to this pandemic, our infrastructure within the agency and around the country was too frail to tackle what we confronted with Covid-19," she said. "To be frank, we are responsible for some pretty dramatic, pretty public mistakes — from testing, to data, to communications."

The CDC overhaul comes on the heels of the agency admitting that "unvaccinated people now have the same guidance as vaccinated people" - and that those exposed to COVID-19 are no longer required to quarantine.

Tyler Durden Wed, 08/17/2022 - 12:22

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Spread & Containment

The Las Vegas Strip Gets a Major New Innovation

It’s not just Caesars and MGM innovating on the Strip. Elon Musk has been tunneling under Las Vegas to solve a big problem, and now he has a rival.

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It's not just Caesars and MGM innovating on the Strip. Elon Musk has been tunneling under Las Vegas to solve a big problem, and now he has a rival.

Las Vegas has quietly become a hotbed for innovation. Some of that has been driven by the major casino operators -- Caesars Entertainment (CZR) - Get Caesars Entertainment Inc. Report, MGM Resorts International (MGM) - Get MGM Resorts International Report, Resorts World Las Vegas, and Wynn Resorts (WYNN) - Get Wynn Resorts Limited Report -- trying to outdo each other to win over customers.

Some innovations are ostentatious and hard to miss, like the MSG (MSGE) - Get Madison Square Garden Entertainment Corp. Class A Report Sphere being built at the Venetian. That first-of-its-kind concert venue looks as if it dropped to Earth from a technologically advanced civilization, and it has raised the bar for performance venues.

Many innovations, however, aren't as obvious. Caesars, for example, uses an artificial intelligence text-based concierge that's surprisingly effective. "Ivy," as it goes by, can answer questions, help with mundane tasks like getting clean towels delivered, or advance your issue to a human where needed.

Innovations big and small are happening up, down, and under the Las Vegas Strip. Elon Musk's Boring Co. has been building a network of tunnels under the city that will eventually use driverless Tesla  (TSLA) - Get Tesla Inc. Report electric vehicles to ferry people all over the city. 

That's a revolutionary idea -- but now a rival has emerged.  

Image source: Daniel Kline/TheStreet

Musk Goes Low, Lyft Goes High?

Musk's Boring Co. has a bold plan for more than 50 stations connecting the Las Vegas Strip to the airport, the Convention Center, Allegiant Stadium, and Fremont Street using driverless Teslas. 

Currently, only a small portion of that network has been built -- a section connecting the two halves of the Las Vegas Convention Center (and one connecting Resorts World Las Vegas to that same location.

For Musk and Boring Co., it's all about taking traffic off the city's busy streets and bringing it underground.

"During typical peak hours, driving from the Las Vegas Convention Center to Mandalay Bay, for example, can take up to 30 minutes. The same trip on Vegas Loop will take approximately 3 minutes," the company says on its website.

If Musk's plan is fully built, it'll effectively give Las Vegas a modern subway, helping alleviate road congestion. It will not, however, stop tourists from using ride-share and taxi cabs.

Now, ride-share company Lyft  (LYFT) - Get Lyft Inc. Report has brought a solution to Sin City that may ultimately help it solve another problem: a shortage of taxi and ride-share drivers. 

Lyft Brings Driverless Cars (Sort of) to Las Vegas

Labor in Las Vegas has been in short supply since the pandemic hit. Some people left the city and others found work outside the service-industry jobs that fuel the Las Vegas economy. At times, that has made the wait for a cab, or a ride-share from Uber (UBER) - Get Uber Technologies Inc. Report and Lyft, longer than usual.

Lyft plans to fix that by partnering with Motional to bring Motional's "Ioniq-5-based robotaxi, an autonomous vehicle designed for fully driverless ride-hail operation, to the Lyft network in Las Vegas," the ride-share company shared in a news release.

The Ioniq 5 is Hyundai's  (HYMTF)  prominent EV. Motional is the Boston joint venture between Hyundai and automotive-technology specialist Aptiv.  (APTV) - Get Aptiv PLC Report

"Launching Motional’s all-electric Ioniq 5 on Lyft’s network in Las Vegas represents tremendous progress in our vision to make an electric, autonomous, and shared future a reality for people everywhere," said  Lyft CEO Logan Green.

An Important Caveat

There is, however, a pretty big catch.

"Each vehicle arrives with not one but two backup drivers standing by to take control of the car should anything go wrong" Casino.org's Corey Levitan reported.

Lyft has promised a truly driverless system at some point in 2023, but current laws and the state of driverless technology make the backups necessary.

Motional and Lyft have quietly been testing driverless vehicles in Las Vegas since 2018. In the news release, Lyft explained how the system works.

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"This means riders are able to easily control their ride without assistance from a driver. The enhanced experience includes unlocking the doors through the Lyft app and starting the ride or contacting customer support from the new in-car Lyft AV app, an intuitive in-ride display tailored to autonomous ride-sharing," the company said.

Lyft and Boring Co. are not working together. But if Musk's plan takes vehicles off Las Vegas's streets, the new program makes the experience better for any that remain. 

Ride sharing and taxis will continue to cost significantly more than using Boring Co's subway-like system, so it's easy to see how the two options will work well together.   .

 

  

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COVID vaccine: how the new ‘bivalent’ booster will target Omicron

The UK has become the first country to approve the shot, which targets omicron alongside the original strain of SARS-CoV-2.

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Prostock-studio/Shutterstock

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has approved a bivalent COVID booster vaccine, making it the first country in the world to do so.

Developed by Moderna, this vaccine has been approved for use in adults, and is set to form part of the upcoming autumn booster campaign in the UK.

But what actually is a bivalent vaccine, and what impact might this booster have on the trajectory of the pandemic? Let’s take a look.


Read more: COVID vaccines: our current shots could soon be updated to target new variants – an immunology expert explains


The COVID vaccines and boosters we currently have, or the first generation, are “monovalent” vaccines. This means they only target the original strain of SARS-CoV-2 (the virus that causes COVID-19).

A recent study suggested that first generation COVID vaccines prevented up to 20 million deaths around the world in their first year of use.

The emergence of the new variants of SARS-CoV-2, including Omicron variants, has been very concerning. Omicron variants are better than earlier non-Omicron variants at evading our immunity from prior infections and vaccines.

Although the vaccines continue to offer protection against deaths and hospital admissions, recent research has shown the initial course of COVID vaccination provides limited protection against symptomatic disease caused by the Omicron variant.

So this second-generation bivalent or dual-variant vaccine targets both the ancestral strain of SARS-CoV-2 and the Omicron variant BA.1. It contains 25 micrograms of original coronavirus vaccine and 25 micrograms of vaccine that specifically targets the Omicron variant.

Likewise, “multivalent” vaccines can protect against even more than two strains of a microbe – though we don’t have any multivalent shots for COVID yet.

Bivalent and multivalent vaccines aren’t new in healthcare. For example, all influenza vaccines available in the UK and the US are quadrivalent, targeting four different strains of flu.

The Gardasil-9 vaccine targets nine strains of the human papillomavirus, a common sexually transmitted infection. Meanwhile, the pneumococcal polysaccharide vaccine, PPSV23, targets an impressive 23 different strains of bacteria that cause pneumococcal diseases, protecting against pneumonia and meningitis, among others.

Safety and efficacy

No serious safety concerns have been identified for this new bivalent vaccine. Any side effects observed during safety monitoring were broadly the same as those seen with the original Moderna booster dose. These are typically mild and get better on their own, such as fever, headache, fatigue or pain at the injection site.

The MHRA’s approval of Moderna’s new bivalent vaccine is based on data from a clinical trial involving more than 400 participants. The results showed that a booster of the bivalent vaccine triggers a strong immune response against both the original Wuhan strain and Omicron BA.1.

Specifically, Moderna reported that in a combined phase 2 and 3 trial, a booster dose of the new bivalent vaccine increased neutralising antibody levels against Omicron BA.1 roughly eight-fold above baseline levels. This was a superior neutralising antibody response when compared with the company’s current monovalent booster.

Notably, Omicron BA.1 was the first Omicron subvariant, but BA.5 is now the dominant variant in the UK and globally. While this vaccine was designed to target BA.1, Moderna have stated the booster also elicited potent neutralising antibody responses against BA.4 and BA.5 compared with the company’s current booster.

These results are promising, but we will need to watch closely for confirmation that they translate beyond clinical trials, and that the vaccine is effective against BA.5 and potentially any new variants in the real word.

An illustration of SARS-CoV-2, the coronavirus that causes COVID-19.
The new bivalent vaccine targets Omicron as well as the ancestral strain of SARS-CoV-2. creativeneko/Shutterstock

In the meantime, Moderna has completed regulatory submissions for its bivalent vaccine in other countries including Canada, Australia and the European Union. Pending authorisation, the vaccine is likely to be available in the US starting in autumn too.

Other pharmaceutical companies including Pfizer and BioNTech are also developing and trialling bivalent boosters to target Omicron.


Read more: COVID vaccines: why second boosters are being offered to vulnerable people in the UK – but not young and healthy people yet


Boosters are a vital weapon against COVID

When immunity from initial vaccine doses wanes, boosters are an important way to increase our immunity. And there’s little doubt that introducing this new Moderna bivalent vaccine will provide substantial protection to many people against COVID, including the newer variants, as we enter the winter months.

At the same time, first-generation boosters are still highly valuable, alongside other precautions we can continue taking to prevent the spread of the virus and new variants. These might include wearing a mask in crowded places, staying away from others when ill, and maintaining good hand hygiene.

COVID remains a threat and we can’t anticipate how the virus will evolve. We may well see the emergence of new variants, creating a need for multivalent vaccines in the future.

Manal Mohammed does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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