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From Alpha to Epsilon: Consortium study illuminates surfaces of Spike most resistant to antibody escape

LA JOLLA, CA—Scientists at La Jolla Institute for Immunology (LJI) have published a detailed map of where human antibodies bind to SARS-CoV-2, a map that was generated by a global collaboration comparing nearly all leading clinical candidates. The new…

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LA JOLLA, CA—Scientists at La Jolla Institute for Immunology (LJI) have published a detailed map of where human antibodies bind to SARS-CoV-2, a map that was generated by a global collaboration comparing nearly all leading clinical candidates. The new research, published in Science, will guide the development of more effective COVID-19 antibody therapies and help scientists develop effective vaccines to address emerging viral variants.

Credit: Reprinted with permission from Hastie et al., Science (2021)

LA JOLLA, CA—Scientists at La Jolla Institute for Immunology (LJI) have published a detailed map of where human antibodies bind to SARS-CoV-2, a map that was generated by a global collaboration comparing nearly all leading clinical candidates. The new research, published in Science, will guide the development of more effective COVID-19 antibody therapies and help scientists develop effective vaccines to address emerging viral variants.

The findings propel COVID-19 research in three key ways:

  • Hundreds of antibodies contributed by over 50 different organizations around the world were classified and mapped. This study shows exactly where each antibody binds on the Spike protein of SARS-CoV-2.
  • The researchers describe the neutralizing strength, or potency, of each antibody and the likelihood that each antibody could offer protection against viral variants.
  • Antibodies with similar footprints on Spike were grouped into “communities.” The researchers show how antibodies from different communities could be combined in a powerful antibody “cocktail” to target the virus.

“We were able to map the geography of Spike and understand which antibodies bind to which footprints. This map provides a reference to help predict  which antibodies are still effective against SARS-CoV-2 variants of concern like the currently surging Delta variant,” says LJI Professor Erica Ollmann Saphire, Ph.D., who leads the global effort behind this research, called the Coronavirus Immunotherapeutic Consortium (CoVIC). 

In fact, the researchers found three different groups of antibodies that are resistant to mutations in SARS-CoV-2 Spike protein. These antibodies could target vulnerable sites on the Spike protein, even as it mutates. 

“We now have a framework for selecting durable antibody cocktails for COVID-19 treatment,” says Saphire.

Gathering powerful antibodies

The CoVIC includes about 370 antibodies from 59 different discovery efforts that cover a broad range: from academic labs and small biotechs to large international pharmaceutical corporations. These antibody therapeutics are being evaluated side-by-side in standardized lab by seven different partner labs. The Saphire team at LJI is determining high-resolution structures of these antibodies and also rapidly generated tools to examine the effects of mutations in Spike on antibody potency.  

“CoVIC was formed to analyze a huge panel of monoclonal antibodies on equal footing,” says study co-first author Kathryn Hastie, Ph.D., an instructor at LJI. “The initial goal was to look at antibodies against the original SARS-CoV-2 strain, but it quickly became clear that the virus’s Spike protein was ever-evolving. The ability of the Spike to change has serious implications when you are talking about treating someone with a monoclonal antibody.”

“The CoVIC contributors used different strategies to find these antibodies,” adds study co-first author Haoyang Li, Ph.D., a postdoctoral fellow at LJI. “This breadth of antibodies makes our study more comprehensive than previous studies that might have looked at antibodies from a small pool of survivors.”

This systematic study on the huge pool of antibodies is a massive undertaking. This study provides a framework to understand, on a global scale, which antibodies are effective (or not) against which variants. This information will be key in narrowing the pool of antibodies from which to advance to further study. “Every member of our 25-person lab pitched in,” says Saphire.

The global effort is coordinated by Program Manager Dr. Sharon Schendel and involves blinding of the array of clinical candidates so all therapeutics are evaluated on an equal playing field. Also at LJI, Professor Bjoern Peters, Ph.D. is leading a team building the CoVIC Database that serves as the publicly available repository for all data collected by CoVIC partner labs. These data are freely accessible to other researchers looking to compare and contrast antibodies against SARS-CoV-2 Spike.  The combined information will help determine which antibodies would be candidates to advance toward clinical use. 

Finding antibody “all stars”

A key site on Spike, called the receptor binding domain (RBD), sticks up like a rocky outcrop, and the Saphire lab scientists took to using mountaineering terms to describe its structure. The inner and outer faces of the RBD are connected by a central “valley”. A “peak” and a “mesa” tower asides. Head over the mesa and you look down on an “escarpment” below. 

By seeing where antibodies bind with the RBD landscape, the researchers separated promising antibodies into “communities.”

“Communities are groups of antibodies that have the same behavior, meaning they can or cannot bind to the Spike protein at the same time as other antibodies,” says Schendel.

Antibodies know how to recognize specific viral structures. They see their targets and latch on to stop a virus from infecting cells. But what if their target mutates and the landscape an antibody recognizes suddenly looks a little different?

“A variant may be discovered weeks after it emerged—it’s an endless game of catch up,” says Saphire. “We needed to know which in our library of antibodies would be durable over the months and years ahead.”

The researchers needed to find antibodies that target “conserved” sites on the RBD. These are the sites that are so important for the viral life cycle that the virus probably couldn’t function if they mutated. The most effective antibodies are ones that target these conserved sites.

To find durable antibodies, Hastie generated a range of Spike proteins with different point mutations. These structures reflect those seen in variants of concern such as Alpha, Gamma and Delta. 

For some antibodies, one or two mutations in Spike were enough to make them lose sight of their target. “We could see which kinds of antibodies were escaped by which mutations,” says Hastie. “That is really useful to know, since we can see these mutations in the real-world variants of concern.”

For example, scientists know that the Beta variant has a mutation at a site called K417N. “We can now identify antibodies that are impacted by mutations at that site, but we can also identify antibodies that would still work against other sites on the Beta variant’s Spike protein,” Hastie says.

Schendel and Hastie worked closely with Daniel Bedinger, Ph.D., of Salt Lake City-based biotech company Carterra®, which developed the LSA® instrument and Epitope binning analysis software that was critical for this analysis. Bedinger created network plots that allowed the scientists to compare how more than 250 antibodies would bind to SARS-CoV-2. These network plots showed which antibodies would bind in the presence of each other—in other words, which antibodies would “play nice” with other antibodies.

“Carterra volunteered to do this work on a pro-bono basis,” says Hastie. “I want to give kudos to Daniel and Carterra.”

The researchers aimed to find the best antibodies from different communities and put them together into an all-star team to take down the virus.

Meanwhile, Li led the structural studies. The team used LJI’s cryo-electron microscopy facility to image antibody structures combined with the RBD.

Through his work, Li assembled a “hit map” of where antibodies targeted the virus. The map shows that seven antibody communities target mutable, or conserved, areas on the Spike. Moreover, in contrast to the conventional studies that use the Fab version for structures, this work use whole IgGs to mimic and reveal how these antibodies protect cells from infection. Some IgGs target to SARS-CoV-2 Spike in a bivalent-binding manner, which increase the affinity and potency of the antibodies, whereas others tend to inactivate virions by cross-linking Spikes. “This is new information to the scientific community, and it is a good example of why we needed this more detailed antibody analysis,” says Li.

Not only did Li lead the structural biology effort, he also made sure that the structures were accessible—both in the paper but also by depositing the structural information in public databases so other scientists could access the data. “Haoyang was the driving force behind getting all these structures,” says Schendel. “His efforts were truly heroic.”

In the end, the researchers assembled a fascinating color-coded library of antibodies within their communities. This work shows which antibodies can be combined in monoclonal antibody therapies. The research also shows which antibodies need to be elicited from future vaccines to maximize protection against SARS-CoV-2 variants.

Science with a global impact

Three of the communities proved especially durable against mutations on the RBD.

“Those antibodies are really good candidates for use in monoclonal antibody therapies,” says Hastie. “If you are making an antibody cocktail, you’d want at least one of those antibodies in there because they are probably going to maintain their efficacy against most variants.”

Some COVID-19 patients can already access monoclonal antibody cocktails. As Schendel explains, the current cocktails have limitations: they work best if given before severe symptoms set in—and they must be given via I.V. in a clinical setting. 

With this new study, the CoVIC is closer to developing more potent antibody therapies that could pack a punch against SARS-CoV-2 variants. More powerful antibody therapies might also be effective at a lower dose, says Schendel, making them a practical option for distribution in countries where medical care is less accessible. She hopes that one day, monoclonal antibody therapies could be given as a simple injection.

The CoVIC team is now working with partners on animal protection studies. Other CoVIC researchers are working to understand how neutralizing antibodies coordinate with immune system responses.

Some people feel that the worst days of the pandemic are long gone, but Americans continue to die of COVID-19, and many people around the world will not receive a COVID-19 vaccine for years.

“We have such a large population in the United States and around the world that is not vaccinated,” says Schendel. “If we can devise better monoclonal antibody therapies, there will be therapies available to them.”

The study, “Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A Global Consortium study,” was supported by the Overton Family (funding to the Coronavirus Immunotherapeutic Consortium); the COVID-19 Therapeutics Accelerator INV-006133 (Coronavirus Immunotherapeutic Consortium); the Bill and Melinda Gates Foundation OPP1210938 (Coronavirus Immunotherapeutic Consortium); The GHR Foundation (Coronavirus Immunotherapeutic Consortium); NIH/NIAID grant U19 AI142790-S1 (Coronavirus Immunotherapeutic Consortium); Carolee Lee; FastGrants from Emergent Ventures at the Mercatus Center; George Mason University for support of essential instrumentation; a Early Postdoc Mobility Fellowship of the Swiss National Science Foundation (P2EZP3_195680); and the Translating Duke Health Immunology Initiative.

Additional study authors include S. Moses, Dennison, Kan Li, Vamseedhar Rayaprolu, Xiaoying Yu, Colin Mann, Michelle Zandonatti, Ruben Diaz Avalos, Dawid Zyla, Tierra Buck, Sean Hui, Kelly Shaffer, Chitra Hariharan, Jieyun Yin, Eduardo Olmedillas, Adrian Enriquez, Diptiben Parekh, Milite Abraha, Elizabeth Feeney, Gillian Q. Horn, CoVIC-DB team, Yoann Aldon, Hanif Ali, Sanja Aracic, Ronald R. Cobb, Ross S. Federman, Joseph M. Fernandez, Jacob Glanville10, Robin Green8 9 , Gevorg Grigoryan, Ana G. Lujan Hernandez, David D. Ho, Kuan-Ying A. Huang, John Ingraham, Weidong Jiang, Paul Kellam, Cheolmin Kim, Minsoo Kim, Hyeong Mi Kim, Chao Kong, Shelly J. Krebs, Fei Lan, Guojun Lang, Sooyoung Lee, Cheuk Lun Leung, Junli Liu, Yanan Lu, Anna MacCamy, Andrew T. McGuire, Anne L. Palser, Terence H. Rabbitts, Zahra Rikhtegaran Tehrani, Mohammad M. Sajadi, Rogier W. Sanders, Aaron K. Sato, Liang Schweizer, Jimin Seo, Bingqing Shen, Jonne J. Snitselaar, Leonidas Stamatatos, Yongcong Tan, Milan T. Tomic, Marit J. van Gils, Sawsan Youssef, Jian Yu, Tom Z. Yuan, Qian Zhang, Georgia D. Tomaras and Timothy Germann.

DOI: 10.1126/science.abh2315

About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal:  life without disease.


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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…

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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 wealth divide

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. 

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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.

personal savings

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.

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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.

credit card 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.

consumer loans credit cards and wages

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.

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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 unemployment rate

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.

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Analyst reviews Apple stock price target amid challenges

Here’s what could happen to Apple shares next.

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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.

Related: Tech News Now: OpenAI says Musk contract 'never existed', Xiaomi's EV, and more

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.

Related: Veteran fund manager picks favorite stocks for 2024

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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…

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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

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.

 

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


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