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…

Published

2 years ago

March 22, 2022

Bioengineer

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

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).

Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2119093119

Article Title

Spherical Nucleic Acids as an Infectious Disease Vaccine Platform

Article Publication Date

21-Mar-2022

Related Topics:aggregated Science vaccine antibodies DNA COVID-19

Up Next

CCP Locks Down China’s “Steel City” As Frustrated Citizens Lash Out In Shanghai

Don't Miss

Building back equitably: 4 ways to address mental health inequities magnified by the pandemic, and ensure access to care

Bioengineer

Bougie Broke The Financial Reality Behind The Facade

Social media users claiming to be Bougie Broke share pictures of their fancy cars, high-fashion clothing, and selfies in exotic locations and expensive…

Published

1 hour ago

March 13, 2024

Michael Lebowitz

Social media users claiming to be Bougie Broke share pictures of their fancy cars, high-fashion clothing, and selfies in exotic locations and expensive restaurants. Yet they complain about living paycheck to paycheck and lacking the means to support their lifestyle.

Bougie broke is like “keeping up with the Joneses,” spending beyond one’s means to impress others.

Bougie Broke gives us a glimpse into the financial condition of a growing number of consumers. Since personal consumption represents about two-thirds of economic activity, it’s worth diving into the Bougie Broke fad to appreciate if a large subset of the population can continue to consume at current rates.

The Wealth Divide Disclaimer

Forecasting personal consumption is always tricky, but it has become even more challenging in the post-pandemic era. To appreciate why we share a joke told by Mike Green.

Bill Gates and I walk into the bar…

Bartender: “Wow… a couple of billionaires on average!”

Bill Gates, Jeff Bezos, Elon Musk, Mark Zuckerberg, and other billionaires make us all much richer, on average. Unfortunately, we can’t use the average to pay our bills.

According to Wikipedia, Bill Gates is one of 756 billionaires living in the United States. Many of these billionaires became much wealthier due to the pandemic as their investment fortunes proliferated.

To appreciate the wealth divide, consider the graph below courtesy of Statista. 1% of the U.S. population holds 30% of the wealth. The wealthiest 10% of households have two-thirds of the wealth. The bottom half of the population accounts for less than 3% of the wealth.

The uber-wealthy grossly distorts consumption and savings data. And, with the sharp increase in their wealth over the past few years, the consumption and savings data are more distorted.

Furthermore, and critical to appreciate, the spending by the wealthy doesn’t fluctuate with the economy. Therefore, the spending of the lower wealth classes drives marginal changes in consumption. As such, the condition of the not-so-wealthy is most important for forecasting changes in consumption.

Ad for financial planning services. Need a plan to protect your hard earned savings from the next bear market? Click to schedule your consultation today.

Revenge Spending

Deciphering personal data has also become more difficult because our spending habits have changed due to the pandemic.

A great example is revenge spending. Per the New York Times:

Ola Majekodunmi, the founder of All Things Money, a finance site for young adults, explained revenge spending as expenditures meant to make up for “lost time” after an event like the pandemic.

So, between the growing wealth divide and irregular spending habits, let’s quantify personal savings, debt usage, and real wages to appreciate better if Bougie Broke is a mass movement or a silly meme.

The Means To Consume

Savings, debt, and wages are the three primary sources that give consumers the ability to consume.

Savings

The graph below shows the rollercoaster on which personal savings have been since the pandemic. The savings rate is hovering at the lowest rate since those seen before the 2008 recession. The total amount of personal savings is back to 2017 levels. But, on an inflation-adjusted basis, it’s at 10-year lows. On average, most consumers are drawing down their savings or less. Given that wages are increasing and unemployment is historically low, they must be consuming more.

Now, strip out the savings of the uber-wealthy, and it’s probable that the amount of personal savings for much of the population is negligible. A survey by Payroll.org estimates that 78% of Americans live paycheck to paycheck.

More on Insufficient Savings

The Fed’s latest, albeit old, Report on the Economic Well-Being of U.S. Households from June 2023 claims that over a third of households do not have enough savings to cover an unexpected $400 expense. We venture to guess that number has grown since then. To wit, the number of households with essentially no savings rose 5% from their prior report a year earlier.

Relatively small, unexpected expenses, such as a car repair or a modest medical bill, can be a hardship for many families. When faced with a hypothetical expense of $400, 63 percent of all adults in 2022 said they would have covered it exclusively using cash, savings, or a credit card paid off at the next statement (referred to, altogether, as “cash or its equivalent”). The remainder said they would have paid by borrowing or selling something or said they would not have been able to cover the expense.

Debt

After periods where consumers drained their existing savings and/or devoted less of their paychecks to savings, they either slowed their consumption patterns or borrowed to keep them up. Currently, it seems like many are choosing the latter option. Consumer borrowing is accelerating at a quicker pace than it was before the pandemic.

The first graph below shows outstanding credit card debt fell during the pandemic as the economy cratered. However, after multiple stimulus checks and broad-based economic recovery, consumer confidence rose, and with it, credit card balances surged.

The current trend is steeper than the pre-pandemic trend. Some may be a catch-up, but the current rate is unsustainable. Consequently, borrowing will likely slow down to its pre-pandemic trend or even below it as consumers deal with higher credit card balances and 20+% interest rates on the debt.

The second graph shows that since 2022, credit card balances have grown faster than our incomes. Like the first graph, the credit usage versus income trend is unsustainable, especially with current interest rates.

With many consumers maxing out their credit cards, is it any wonder buy-now-pay-later loans (BNPL) are increasing rapidly?

Insider Intelligence believes that 79 million Americans, or a quarter of those over 18 years old, use BNPL. Lending Tree claims that “nearly 1 in 3 consumers (31%) say they’re at least considering using a buy now, pay later (BNPL) loan this month.”More telling, according to their survey, only 52% of those asked are confident they can pay off their BNPL loan without missing a payment!

Wage Growth

Wages have been growing above trend since the pandemic. Since 2022, the average annual growth in compensation has been 6.28%. Higher incomes support more consumption, but higher prices reduce the amount of goods or services one can buy. Over the same period, real compensation has grown by less than half a percent annually. The average real compensation growth was 2.30% during the three years before the pandemic.

In other words, compensation is just keeping up with inflation instead of outpacing it and providing consumers with the ability to consume, save, or pay down debt.

It’s All About Employment

The unemployment rate is 3.9%, up slightly from recent lows but still among the lowest rates in the last seventy-five years.

The uptick in credit card usage, decline in savings, and the savings rate argue that consumers are slowly running out of room to keep consuming at their current pace.

However, the most significant means by which we consume is income. If the unemployment rate stays low, consumption may moderate. But, if the recent uptick in unemployment continues, a recession is extremely likely, as we have seen every time it turned higher.

It’s not just those losing jobs that consume less. Of greater impact is a loss of confidence by those employed when they see friends or neighbors being laid off.

Accordingly, the labor market is probably the most important leading indicator of consumption and of the ability of the Bougie Broke to continue to be Bougie instead of flat-out broke!

Summary

There are always consumers living above their means. This is often harmless until their means decline or disappear. The Bougie Broke meme and the ability social media gives consumers to flaunt their “wealth” is a new medium for an age-old message.

Diving into the data, it argues that consumption will likely slow in the coming months. Such would allow some consumers to save and whittle down their debt. That situation would be healthy and unlikely to cause a recession.

The potential for the unemployment rate to continue higher is of much greater concern. The combination of a higher unemployment rate and strapped consumers could accentuate a recession.

The post Bougie Broke The Financial Reality Behind The Facade appeared first on RIA.

recession unemployment pandemic economic recovery stimulus fed recession recovery interest rates unemployment stimulus

International

Analyst reviews Apple stock price target amid challenges

Here’s what could happen to Apple shares next.

Published

10 hours ago

March 12, 2024

Rob Lenihan

They said it was bound to happen.

It was Jan. 11, 2024 when software giant Microsoft (MSFT) briefly passed Apple (AAPL) as the most valuable company in the world.

Microsoft's stock closed 0.5% higher, giving it a market valuation of $2.859 trillion.

It rose as much as 2% during the session and the company was briefly worth $2.903 trillion. Apple closed 0.3% lower, giving the company a market capitalization of $2.886 trillion.

"It was inevitable that Microsoft would overtake Apple since Microsoft is growing faster and has more to benefit from the generative AI revolution," D.A. Davidson analyst Gil Luria said at the time, according to Reuters.

The two tech titans have jostled for top spot over the years and Microsoft was ahead at last check, with a market cap of $3.085 trillion, compared with Apple's value of $2.684 trillion.

Analysts noted that Apple had been dealing with weakening demand, including for the iPhone, the company’s main source of revenue.

Demand in China, a major market, has slumped as the country's economy makes a slow recovery from the pandemic and competition from Huawei.

Sales in China of Apple's iPhone fell by 24% in the first six weeks of 2024 compared with a year earlier, according to research firm Counterpoint, as the company contended with stiff competition from a resurgent Huawei "while getting squeezed in the middle on aggressive pricing from the likes of OPPO, vivo and Xiaomi," said senior Analyst Mengmeng Zhang.

“Although the iPhone 15 is a great device, it has no significant upgrades from the previous version, so consumers feel fine holding on to the older-generation iPhones for now," he said.

A man scrolling through Netflix on an Apple iPad Pro. Photo by Phil Barker/Future Publishing via Getty Images.

Future Publishing/Getty Images

Big plans for China

Counterpoint said that the first six weeks of 2023 saw abnormally high numbers with significant unit sales being deferred from December 2022 due to production issues.

Apple is planning to open its eighth store in Shanghai – and its 47th across China – on March 21.

The company also plans to expand its research centre in Shanghai to support all of its product lines and open a new lab in southern tech hub Shenzhen later this year, according to the South China Morning Post.

Meanwhile, over in Europe, Apple announced changes to comply with the European Union's Digital Markets Act (DMA), which went into effect last week, Reuters reported on March 12.

Beginning this spring, software developers operating in Europe will be able to distribute apps to EU customers directly from their own websites instead of through the App Store.

"To reflect the DMA’s changes, users in the EU can install apps from alternative app marketplaces in iOS 17.4 and later," Apple said on its website, referring to the software platform that runs iPhones and iPads.

"Users will be able to download an alternative marketplace app from the marketplace developer’s website," the company said.

Apple has also said it will appeal a $2 billion EU antitrust fine for thwarting competition from Spotify (SPOT) and other music streaming rivals via restrictions on the App Store.

The company's shares have suffered amid all this upheaval, but some analysts still see good things in Apple's future.

Bank of America Securities confirmed its positive stance on Apple, maintaining a buy rating with a steady price target of $225, according to Investing.com.

The firm's analysis highlighted Apple's pricing strategy evolution since the introduction of the first iPhone in 2007, with initial prices set at $499 for the 4GB model and $599 for the 8GB model.

BofA said that Apple has consistently launched new iPhone models, including the Pro/Pro Max versions, to target the premium market.

Analyst says Apple selloff 'overdone'

Concurrently, prices for previous models are typically reduced by about $100 with each new release.

This strategy, coupled with installment plans from Apple and carriers, has contributed to the iPhone's installed base reaching a record 1.2 billion in 2023, the firm said.

More Tech Stocks:

Apple has effectively shifted its sales mix toward higher-value units despite experiencing slower unit sales, BofA said.

This trend is expected to persist and could help mitigate potential unit sales weaknesses, particularly in China.

BofA also noted Apple's dominance in the high-end market, maintaining a market share of over 90% in the $1,000 and above price band for the past three years.

The firm also cited the anticipation of a multi-year iPhone cycle propelled by next-generation AI technology, robust services growth, and the potential for margin expansion.

On Monday, Evercore ISI analysts said they believed that the sell-off in the iPhone maker’s shares may be “overdone.”

The firm said that investors' growing preference for AI-focused stocks like Nvidia (NVDA) has led to a reallocation of funds away from Apple.

In addition, Evercore said concerns over weakening demand in China, where Apple may be losing market share in the smartphone segment, have affected investor sentiment.

And then ongoing regulatory issues continue to have an impact on investor confidence in the world's second-biggest company.

“We think the sell-off is rather overdone, while we suspect there is strong valuation support at current levels to down 10%, there are three distinct drivers that could unlock upside on the stock from here – a) Cap allocation, b) AI inferencing, and c) Risk-off/defensive shift," the firm said in a research note.

stocks pandemic recovery european europe eu china

International

Major typhoid fever surveillance study in sub-Saharan Africa indicates need for the introduction of typhoid conjugate vaccines in endemic countries

There is a high burden of typhoid fever in sub-Saharan African countries, according to a new study published today in The Lancet Global Health. This high…

Published

10 hours ago

March 12, 2024

Bioengineer

There is a high burden of typhoid fever in sub-Saharan African countries, according to a new study published today in The Lancet Global Health. This high burden combined with the threat of typhoid strains resistant to antibiotic treatment calls for stronger prevention strategies, including the use and implementation of typhoid conjugate vaccines (TCVs) in endemic settings along with improvements in access to safe water, sanitation, and hygiene.

Credit: IVI

The findings from this 4-year study, the Severe Typhoid in Africa (SETA) program, offers new typhoid fever burden estimates from six countries: Burkina Faso, Democratic Republic of the Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria, with four countries recording more than 100 cases for every 100,000 person-years of observation, which is considered a high burden. The highest incidence of typhoid was found in DRC with 315 cases per 100,000 people while children between 2-14 years of age were shown to be at highest risk across all 25 study sites.

There are an estimated 12.5 to 16.3 million cases of typhoid every year with 140,000 deaths. However, with generic symptoms such as fever, fatigue, and abdominal pain, and the need for blood culture sampling to make a definitive diagnosis, it is difficult for governments to capture the true burden of typhoid in their countries.

“Our goal through SETA was to address these gaps in typhoid disease burden data,” said lead author Dr. Florian Marks, Deputy Director General of the International Vaccine Institute (IVI). “Our estimates indicate that introduction of TCV in endemic settings would go to lengths in protecting communities, especially school-aged children, against this potentially deadly—but preventable—disease.”

In addition to disease incidence, this study also showed that the emergence of antimicrobial resistance (AMR) in Salmonella Typhi, the bacteria that causes typhoid fever, has led to more reliance beyond the traditional first line of antibiotic treatment. If left untreated, severe cases of the disease can lead to intestinal perforation and even death. This suggests that prevention through vaccination may play a critical role in not only protecting against typhoid fever but reducing the spread of drug-resistant strains of the bacteria.

There are two TCVs prequalified by the World Health Organization (WHO) and available through Gavi, the Vaccine Alliance. In February 2024, IVI and SK bioscience announced that a third TCV, SKYTyphoid™, also achieved WHO PQ, paving the way for public procurement and increasing the global supply.

Alongside the SETA disease burden study, IVI has been working with colleagues in three African countries to show the real-world impact of TCV vaccination. These studies include a cluster-randomized trial in Agogo, Ghana and two effectiveness studies following mass vaccination in Kisantu, DRC and Imerintsiatosika, Madagascar.

Dr. Birkneh Tilahun Tadesse, Associate Director General at IVI and Head of the Real-World Evidence Department, explains, “Through these vaccine effectiveness studies, we aim to show the full public health value of TCV in settings that are directly impacted by a high burden of typhoid fever.” He adds, “Our final objective of course is to eliminate typhoid or to at least reduce the burden to low incidence levels, and that’s what we are attempting in Fiji with an island-wide vaccination campaign.”

As more countries in typhoid endemic countries, namely in sub-Saharan Africa and South Asia, consider TCV in national immunization programs, these data will help inform evidence-based policy decisions around typhoid prevention and control.

###

About the International Vaccine Institute (IVI)
The International Vaccine Institute (IVI) is a non-profit international organization established in 1997 at the initiative of the United Nations Development Programme with a mission to discover, develop, and deliver safe, effective, and affordable vaccines for global health.

IVI’s current portfolio includes vaccines at all stages of pre-clinical and clinical development for infectious diseases that disproportionately affect low- and middle-income countries, such as cholera, typhoid, chikungunya, shigella, salmonella, schistosomiasis, hepatitis E, HPV, COVID-19, and more. IVI developed the world’s first low-cost oral cholera vaccine, pre-qualified by the World Health Organization (WHO) and developed a new-generation typhoid conjugate vaccine that is recently pre-qualified by WHO.

IVI is headquartered in Seoul, Republic of Korea with a Europe Regional Office in Sweden, a Country Office in Austria, and Collaborating Centers in Ghana, Ethiopia, and Madagascar. 39 countries and the WHO are members of IVI, and the governments of the Republic of Korea, Sweden, India, Finland, and Thailand provide state funding. For more information, please visit https://www.ivi.int.

CONTACT

Aerie Em, Global Communications & Advocacy Manager
+82 2 881 1386 | aerie.em@ivi.int