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New data suggests COVID vaccine design ideas with better variant resilience

Latest research findings show that vaccine-elicited neutralizing antibodies against SARS-CoV-2 are mostly directed against one of the two main domains…

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Latest research findings show that vaccine-elicited neutralizing antibodies against SARS-CoV-2 are mostly directed against one of the two main domains of the viral entry machinery.

Credit: Veesler Lab/UW Medicine

Latest research findings show that vaccine-elicited neutralizing antibodies against SARS-CoV-2 are mostly directed against one of the two main domains of the viral entry machinery.

The findings also point out a key role of the same domain of the spike in eliciting a broad antibody response against many variants, as well as related viruses.

Both findings suggest strategies for clinical development of variant-resistant vaccines and sarbecovirus vaccines as part of future pandemic preparedness.

Spike proteins, which give the virus its crown-like appearance, provide the means for the virus to enter host cells. One subunit of the spike protein engages with a receptor on the host cell and recognizes when a proper landing has occurred.

The spike also adopts a spring-loaded configuration. Its shape changes as it forces the fusion of the virus to the host cell, thereby initiating infection.

Antibodies try to ward off a SARS-CoV-2 invasion of cells by binding to sites on the viral spike protein. A wide range of currently available vaccinations, or the immune system’s own response to a bout of COVID-19, can elicit such antibodies.

An international research team led by David Veesler, associate professor of biochemistry at the University of Washington in Seattle and a Howard Hughes Medical Institute Investigator, decided to look, using cryoelectron microscopy and other methods, at the specificity of spike protein-directed antibody responses. They wanted to assess the relative contribution of the binding site of the antibody to neutralizing activity against SARS-COV-2 variants.

Through this, and related work, they wanted to understand the influence of the varying spike protein conformations on blood-plasma antibody neutralizing activity. Such information might help in discovering ways to modulate the magnitude and breadth of antibodies against SARS-CoV-2.

The researchers studied plasma samples from individuals who had not been exposed to COVID-19, but who had received the primary series of doses of one of the seven most administered vaccinations worldwide. In addition, they examine samples from subjects who had a history of infection and vaccination. They also looked a convalescent plasma from people who had acquired COVID-19 before January 2021, when vaccination programs started.

Their results are published in Science Immunology Nov. 10. The paper is titled SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines. The lead author of the paper is John E. Bowen of the Veesler Lab.

The scientists observed a strong correlation between in vitro virus inhibitory activity of participant plasma and the magnitude of antibody responses against the prefusion form of the spike protein. This was true for all the vaccines evaluated and for antibodies induced by previous infection.

“We observed a comparable positive correlation between antibody neutralizing activity and S1 binding antibody responses, suggesting a key role of S1-directed antibodies for SARS-CoV-2 neutralization,” the researchers wrote. S1 is the spike protein unit involved in host cell receptor engagement, the first part of the viral attack on a cell.

The researchers also found that neutralizing antibody plasma samples also corresponded to the presence of antibodies that specifically targeted two domains on the S1 spike protein unit. Earlier studies had suggested that those two domains, named NTD and RBD, were the main targets of neutralizing antibody responses during an infection or after vaccination.

These NTD and RBD-directed host antibodies may also in part account for evolutionary selective pressure on those parts of the virus. This selective pressure may have led to a rapid accumulation of mutations in variants to try to outwit this immune strategy, the scientists suggested.

The researchers also found that antibodies against the RBD site account for the greater breadth of cross-neutralizing antibody response, against a number of SARS-CoV-2 variants, compared to the narrower focus of antibodies that homed in on the NTD site.

“Multiple broadly neutralizing sarbecovirus antibodies recognize distinct RBD antigenic sites,” the researchers noted. Sarbecovirus is the larger group of viruses that include the pandemic coronavirus.

On the other hand, targeting the S2 subunit, which is the part of the spike involved in membrane fusion, did not contribute much to vaccine-elicited neutralizing activity. Such antibodies were few and weak in potency.

The findings, the researchers concluded, suggest the potential usefulness of developing RBD-based vaccines against SARS-CoV-2 and the larger group of related sarbecoviruses as part of future pandemic preparedness.

This study was supported by the National Institute of Allergy and Infectious Diseases (DP1AI158186, 75N93022C00036, U01 AI151698), National Institute of General Medical Sciences (R01GM120553 ), Pew Biomedical Scholars Award, an Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund, Fast Grants, Bill & Melinda Gates Foundation (OPP1156262 ), University of Washington Arnold and Mabel Beckman cryoEM center and the National Institute of Health grant S10OD032290  and grant U01 AI151698 for the United World Antiviral Research Network as part of the Centers for Research in Emerging Infectious Diseases Network.

Competing interests are listed in the Science Immunology paper.

 


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US gov’t $1.5T debt interest will be equal 3X Bitcoin market cap in 2023

The U.S. will pay over $1 trillion in debt interest next year, the equivalent of three or more Bitcoin market caps at current prices.

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The U.S. will pay over $1 trillion in debt interest next year, the equivalent of three or more Bitcoin market caps at current prices.

Commentators believe that Bitcoin (BTC) bulls do not need to wait long for the United States to start printing money again.

The latest analysis of U.S. macroeconomic data has led one market strategist to predict quantitative tightening (QT) ending to avoid a “catastrophic debt crisis.”

Analyst: Fed will have “no choice” with rate cuts

The U.S. Federal Reserve continues to remove liquidity from the financial system to fight inflation, reversing years of COVID-19-era money printing.

While interest rate hikes look set to continue declining in scope, some now believe that the Fed will soon have only one option — to halt the process altogether.

“Why the Fed will have no choice but to cut or risk a catastrophic debt crisis,” Sven Henrich, founder of NorthmanTrader, summarized on Jan. 27.

“Higher for longer is a fantasy not rooted in math reality.”

Henrich uploaded a chart showing interest payments on current U.S. government expenditure, now hurtling toward $1 trillion a year.

A dizzying number, the interest comes from U.S. government debt being over $31 trillion, with the Fed printing trillions of dollars since March 2020. Since then, interest payments have increased by 42%, Henrich noted.

The phenomenon has not gone unnoticed elsewhere in crypto circles. Popular Twitter account Wall Street Silver compared the interest payments as a portion of U.S. tax revenue.

“US paid $853 Billion in Interest for $31 Trillion Debt in 2022; More than Defense Budget in 2023. If the Fed keeps rates at these levels (or higher) we will be at $1.2 trillion to $1.5 trillion in interest paid on the debt,” it wrote.

“The US govt collects about $4.9 trillion in taxes.”
Interest rates on U.S. government debt chart (screenshot). Source: Wall Street Silver/ Twitter

Such a scenario might be music to the ears of those with significant Bitcoin exposure. Periods of “easy” liquidity have corresponded with increased appetite for risk assets across the mainstream investment world.

The Fed’s unwinding of that policy accompanied Bitcoin’s 2022 bear market, and a “pivot” in interest rate hikes is thus seen by many as the first sign of the “good” times returning.

Crypto pain before pleasure?

Not everyone, however, agrees that the impact on risk assets, including crypto, will be all-out positive prior to that.

Related: Bitcoin ‘so bullish’ at $23K as analyst reveals new BTC price metrics

As Cointelegraph reported, ex-BitMEX CEO Arthur Hayes believes that chaos will come first, tanking Bitcoin and altcoins to new lows before any sort of long-term renaissance kicks in.

If the Fed faces a complete lack of options to avoid a meltdown, Hayes believes that the damage will have already been done before QT gives way to quantitative easing.

“This scenario is less ideal because it would mean that everyone who is buying risky assets now would be in store for massive drawdowns in performance. 2023 could be just as bad as 2022 until the Fed pivots,” he wrote in a blog post this month.

The views, thoughts and opinions expressed here are the authors’ alone and do not necessarily reflect or represent the views and opinions of Cointelegraph.

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Stay Ahead of GDP: 3 Charts to Become a Smarter Trader

When concerns of a recession are front and center, investors tend to pay more attention to the Gross Domestic Product (GDP) report. The Q4 2022 GDP report…

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When concerns of a recession are front and center, investors tend to pay more attention to the Gross Domestic Product (GDP) report. The Q4 2022 GDP report showed the U.S. economy grew by 2.9% in the quarter, and Wall Street wasn't disappointed. The day the report was released, the market closed higher, with the Dow Jones Industrial Average ($DJIA) up 0.61%, the S&P 500 index ($SPX) up 1.1%, and the Nasdaq Composite ($COMPQ) up 1.76%. Consumer Discretionary, Technology, and Energy were the top-performing S&P sectors.

Add to the GDP report strong earnings from Tesla, Inc. (TSLA) and a mega announcement from Chevron Corp. (CVX)—raising dividends and a $75 billion buyback round—and you get a strong day in the stock markets.

Why is the GDP Report Important?

If a country's GDP is growing faster than expected, it could be a positive indication of economic strength. It means that consumer spending, business investment, and exports, among other factors, are going strong. But the GDP is just one indicator, and one indicator doesn't necessarily tell the whole story. It's a good idea to look at other indicators, such as the unemployment rate, inflation, and consumer sentiment, before making a conclusion.

Inflation appears to be cooling, but the labor market continues to be strong. The Fed has stated in many of its previous meetings that it'll be closely watching the labor market. So that'll be a sticky point as we get close to the next Fed meeting. Consumer spending is also strong, according to the GDP report. But that could have been because of increased auto sales and spending on services such as health care, personal care, and utilities. Retail sales released earlier in January indicated that holiday sales were lower.

There's a chance we could see retail sales slowing in Q1 2023 as some households run out of savings that were accumulated during the pandemic. This is something to keep an eye on going forward, as a slowdown in retail sales could mean increases in inventories. And this is something that could decrease economic activity.

Overall, the recent GDP report indicates the U.S. economy is strong, although some economists feel we'll probably see some downside in 2023, though not a recession. But the one drawback of the GDP report is that it's lagging. It comes out after the fact. Wouldn't it be great if you had known this ahead of time so you could position your trades to take advantage of the rally? While there's no way to know with 100% accuracy, there are ways to identify probable events.

3 Ways To Stay Ahead of the Curve

Instead of waiting for three months to get next quarter's GDP report, you can gauge the potential strength or weakness of the overall U.S. economy. Steven Sears, in his book The Indomitable Investor, suggested looking at these charts:

  • Copper prices
  • High-yield corporate bonds
  • Small-cap stocks

Copper: An Economic Indicator

You may not hear much about copper, but it's used in the manufacture of several goods and in construction. Given that manufacturing and construction make up a big chunk of economic activity, the red metal is more important than you may have thought. If you look at the chart of copper futures ($COPPER) you'll see that, in October 2022, the price of copper was trading sideways, but, in November, its price rose and trended quite a bit higher. This would have been an indication of a strengthening economy.

CHART 1: COPPER CONTINUOUS FUTURES CONTRACTS. Copper prices have been rising since November 2022. Chart source: StockCharts.com. For illustrative purposes only.

High-Yield Bonds: Risk On Indicator

The higher the risk, the higher the yield. That's the premise behind high-yield bonds. In short, companies that are leveraged, smaller, or just starting to grow may not have the solid balance sheets that more established companies are likely to have. If the economy slows down, investors are likely to sell the high-yield bonds and pick up the safer U.S. Treasury bonds.

Why the flight to safety? It's because when the economy is sluggish, the companies that issue the high-yield bonds tend to find it difficult to service their debts. When the economy is expanding, the opposite happens—they tend to perform better.

The chart below of the Dow Jones Corporate Bond Index ($DJCB) shows that, since the end of October 2022, the index trended higher. Similar to copper prices, high-yield corporate bond activity was also indicating economic expansion. You'll see similar action in charts of high-yield bond exchange-traded funds (ETFs) such as iShares iBoxx $ High Yield Corporate Bond ETF (HYG) and SPDR Barclays High Yield Bond ETF (JNK).

CHART 2: HIGH-YIELD BONDS TRENDING HIGHER. The Dow Jones Corporate Bond Index ($DJCB) has been trending higher since end of October 2022.Chart source: StockCharts.com. For illustrative purposes only.

Small-Cap Stocks: They're Sensitive

Pull up a chart of the iShares Russell 2000 ETF (IWM) and you'll see similar price action (see chart 3). Since mid-October, small-cap stocks (the Russell 2000 index is made up of 2000 small companies) have been moving higher.

CHART 3: SMALL-CAP STOCKS TRENDING HIGHER. When the economy is expanding, small-cap stocks trend higher.Chart source: StockCharts.com. For illustrative purposes only.

Three's Company

If all three of these indicators are showing strength, you can expect the GDP number to be strong. There are times when the GDP number may not impact the markets, but, when inflation is a problem and the Fed is trying to curb it by raising interest rates, the GDP number tends to impact the markets.

This scenario is likely to play out in 2023, so it would be worth your while to set up a GDP Tracker ChartList. Want a live link to the charts used in this article? They're all right here.


Jayanthi Gopalakrishnan

Director, Site Content

StockCharts.com

 

Disclaimer: This blog is for educational purposes only and should not be construed as financial advice. The ideas and strategies should never be used without first assessing your own personal and financial situation, or without consulting a financial professional.

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Hotels: Occupancy Rate Down 6.2% Compared to Same Week in 2019

From CoStar: STR: MLK Day Leads to Slightly Lower US Weekly Hotel PerformanceWith the Martin Luther King Jr. holiday, U.S. hotel performance came in slightly lower than the previous week, according to STR‘s latest data through Jan. 21.Jan. 15-21, 2023 …

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With the Martin Luther King Jr. holiday, U.S. hotel performance came in slightly lower than the previous week, according to STR‘s latest data through Jan. 21.

Jan. 15-21, 2023 (percentage change from comparable week in 2019*):

Occupancy: 54.2% (-6.2%)
• Average daily rate (ADR): $140.16 (+11.3%)
• evenue per available room (RevPAR): $75.97 (+4.4%)

*Due to the pandemic impact, STR is measuring recovery against comparable time periods from 2019. Year-over-year comparisons will once again become standard after Q1.
emphasis added
The following graph shows the seasonal pattern for the hotel occupancy rate using the four-week average.

Click on graph for larger image.

The red line is for 2023, black is 2020, blue is the median, and dashed light blue is for 2022.  Dashed purple is 2019 (STR is comparing to a strong year for hotels).

The 4-week average of the occupancy rate is below the median rate for the previous 20 years (Blue), but this is the slow season - and some of the early year weakness might be related to the timing of the report.

Note: Y-axis doesn't start at zero to better show the seasonal change.

The 4-week average of the occupancy rate will increase seasonally over the next few months.

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