NEWS POST: Africa’s Answer To 70-Year Old Problem Of How To Beat Repeat Infections

The original antigenic sin has made fighting diseases really difficult. Shutterstock

Dr Wilfred Ndifon has proposed a solution to a 70-year old immunological mystery relating to the original antigenic sin. This complex problem has played havoc with efforts to fight infectious diseases, particularly in places such as Africa where people can suffer successive infections. Ndifon and Tolullah Oni are two of 12 Next Einstein Forum Fellows working to solve major challenges in health, education, big data and quantum theory using science, technology, engineering and mathematics.

What is the original antigenic sin?

The original antigenic sin was first reported about 70 years ago by American epidemiologist Thomas Francis Jr. But its underlying biological mechanisms are still poorly understood.

This much we know: the human body activates white blood cells to fight an infection. When a new infection comes along the white blood cells are activated again. But they are less effective at fighting the new agent. This makes the body much less able to fight the new disease. This is what Thomas Francis described as the original antigenic sin.

The length of time over which original antigenic sin can occur depends on how long the immune system’s memory of a previous infection lasts, which in turn depends on the infecting pathogen. For pathogens like flu viruses, the immune system’s memory can persist throughout an individual’s lifetime.

The same problem arises when a person is treated with a vaccine to fight pathogen A. When that person is infected by a related pathogen B, the vaccine focuses on pathogen A making it less effective.

Why does this matter?

The original antigenic sin makes fighting diseases really difficult. This is because it reduces the effectiveness of vaccines. This happens because vaccines preferentially reactivate previously activated white blood cells. So past infections increase the risk for more severe future infections and for reduced vaccine effectiveness.

This risk is particularly high in sub-Saharan Africa where infections tend to occur frequently. The risk is high in regions where infections occur frequently simply because you need sequential infections with related pathogens in order for original antigenic sin to manifest.

So, the more infections there are, the more likely it is that the body’s defences will be compromised by original antigenic sin. This is also pertinent in the Northern Hemisphere where there are frequent sequential infections by related variants of flu viruses. This creates an ideal environment for original antigenic sin to manifest.

It is also important in other parts of the world where flu is prevalent.

Scientists have documented many instances of the original antigenic sin in humans, mice, and other organisms.

It has been beautifully illustrated in mice that were infected either with only one variant of the flu virus or with that variant followed a month later by another related variant. While the mice infected with only one variant were able to completely control a subsequent infection with that variant, those that were sequentially infected had about 10 000 times more virus in their lungs as a result of original antigenic sin.

NEF Fellow Wilfred Ndifon on how he solved 70 year old immunological problem.

Can you give a practical example?

Imagine for a minute that you have malaria.

The immune system contains specialized white blood cells that are responsible for protecting the body from pathogens which cause malaria.

When the immune system is exposed to the pathogen, the pathogen is chopped into pieces called antigens. Then it is loaded onto the surface of other white blood cells. The white blood cells then become activated. They are then able to get rid of the malaria.

A small number of these white blood cells remain after the pathogen has been eliminated. They stay behind to enable a swift response to any infection by the same pathogen.

After eliminating malaria, let’s imagine you are infected by a new variant of the pathogen. Normally the body should unleash the same process. But this is not always the case.

In some cases, the white blood cells do not recognize the new pathogen. Instead, they focus on the previous pathogen. An earlier theory suggested that this may result from competition among certain white blood cells called B cells. In immunology this is called the original antigenic sin.

So what’s the solution?

My study introduced and confirmed an original theory using mathematics and experimental data. My theory explains why original antigenic sin occurs. It is also the first theory to explain how original antigenic sin can be alleviated by a substance that is added to a vaccine to better activate the immune system’s cells. What we call an adjuvant.

I show that both original antigenic sin and its alleviation by adjuvants arise from the activity of certain white blood cells called T regulatory cells.

T regulatory cells activated by previous pathogens weaken certain white blood cells' ability to load new pathogens onto their surface. This in turn causes fewer white blood cells to become activated, thereby making it difficult for the body to fight new pathogens and leading to original antigenic sin.

But my theory predicts that adjuvants will reduce the inhibition of white blood cell activation that is caused by T regulatory cells, thereby alleviating original antigenic sin.

My discovery opens up additional possibilities for preventing the destructive health consequences of original antigenic sin. For example, it suggests how original antigenic sin can be prevented from reducing a vaccine’s effectiveness. This can be done by designing vaccines so that their components better latch onto the surface of certain white blood cells.

This will counter the effect of the T regulatory cells and make the immune system more effective at getting rid of the pathogens targeted by the vaccine.

Wilfred Ndifon (Left)

Research Chair with joint appointments at both the South African and the Ghanaian centres of the African Institute for Mathematical Sciences. He is also affiliated to the Department of Mathematical Sciences, Stellenbosch University.

 Tolullah Oni (Right)

Senior Lecturer at the School of Public Health and Family Medicine, University of Cape Town.

Originally published in The Conversation

NEWS POST (2-IN-1): 'Resurrection Plants' Offer Hope As Climate Turns Hostile

Jill Farrant, a professor of molecular and cell biology at the University of Cape Town, hopes that unlocking the genetic codes of drought-tolerant plants could help farmers toiling in increasingly hot and dry conditions ©Stephane de Sakutin (AFP)

As the race to adapt to climate change quickens, a South African scientist is leading global research into developing crops that mimic the extraordinary survival skills of "resurrection plants".

Jill Farrant, a professor of molecular and cell biology at the University of Cape Town, hopes that unlocking the genetic codes of drought-tolerant plants could help farmers toiling in increasingly hot and dry conditions.

With more than 130 known varieties in the world, resurrection plants are a unique group of flora that can survive extreme water shortages for years.

During a drought, the plant acts like a seed, becoming so dry it appears dead.

But when the skies finally open and the rain pours down, the shrivelled plant bursts "back to life", turning green and robust in just a few hours.

"I want to cater to the subsistence farmer, the person who wants to make enough food to live," Farrant, 55, told AFP.

"Farmers are becoming more and more dispirited, and droughts are killing them."

Perhaps the most well-known resurrection plant is Myrothamnus flabellifolius, which makes antioxidant chemicals to protect it during dry spells and is used in fashion designer Giorgio Armani's cosmetics line.

- A life passion -

A farmer's daughter, Farrant recalls stumbling across a resurrection plant as a nine-year-old and being amazed at its seemingly immortal properties.

"I wrote in my diary about a plant that had died and came back after the rain," she said.

She returned to the subject professionally in 1994, and has since become the world's leading expert in her field.

Environmentalists fear that more and more of Africa will be reduced to a dust bowl by global warming, with higher temperatures, reduced water supplies and population growth threatening to trigger worsening famines.

Climate change could reduce maize yields across southern Africa by as much as 30 percent by 2030, according to the UN Environment Programme.

Ahead of the United Nations conference in Paris at the end of November, countries are facing growing pressure to keep global warming below two degrees celsius (3.6 degrees Fahrenheit) above pre-Industrial Revolution levels by weaning their carbon-hungry societies off fossil fuels.

But, scientists say it is just as important to adapt to the new reality.

"Soil, cropping systems, farming systems -- they all must have the capacity to recover from a drastic change in climate," said Rattan Lal, professor of soil science at Ohio State University.

"We should make agriculture part of the solution to our issues... the climate change problem is so huge everything should be on the table."

If successful, Farrant will follow in the venerable footsteps of earlier scientists who have saved crops from devastation by exploiting plants with specific strengths.

In the 1970s, US maize was rescued from southern leaf blight disease by incorporating resistant genes found in other varieties of maize.

- Adapt to survive -

Farrant has recently focused her research on teff, a grass native to Ethiopia whose seed has been used as a stable food in the region for centuries.

She hopes to make it more resilient by activating genes she discovered by studying resurrection plants.

"My main aim all along is to make crops that can improve drought tolerance," Farrant told AFP.

"If we get the money, I would say in 10 to 15 years we've got a product."

Experts warn that drought-tolerant crops are not a one-stop solution to the world's climate problems or even a safeguard against hunger.

"Food security doesn't only depend on climate, it depends on markets and trade, prices and access by households to food," said Jim Verdin, a drought scientist with the US Geological Survey based in Boulder, Colorado.

Still, Farrant -- who won a UNESCO Awards for Women in Science in 2012 -- believes her work is a step in the right direction.

If she can harness the power of resurrection plants, farmers themselves may have a better chance of survival.

"If it doesn't rain, it doesn't matter, at least your plants won't die," she said. "The moment they get rain, they're ready to go."

Teff - Ethiopia’s Tiny Secret Going Global

Ethiopia’s indigenous grain teff is garnering global interest as a new super food, while Ethiopia’s government tries to ensure local prices don’t rocket for Ethiopians.

Every six days a week an Ethiopian Airlines flight departs Addis Ababa for Washington in the US with a fresh batch of 3,000 injera on board. This pancake-shaped grey spongy bread is a centuries-old Ethiopian staple made from teff, a tiny grain now making a health food name for itself globally. "For the future this company is planning to distribute Ethiopian traditional food all over the world," said Hailu Tessema, founder of Mama Fresh, Ethiopia's first large-scale factory producing teff-based products.

Inside the factory there are several tall blue barrels full of teff flour mixed with water. The mixture is left there for four days to ferment. Afterwards the fermented mixture is moved next door where women scoop out small jug-sized amounts to pour onto a heated clay surface where it sizzles and turns into a pancake like bread which is called injera.

Calcium, iron, protein, amino acids

Teff's tiny seeds are high in calcium, iron, protein and amino acids and it is also gluten-free. Even before the modern state of Ethiopia existed, Ethiopians have been grinding teff into flour to make injera, remaining unaware of the nutritional gem in their midst. But increasing global demand for healthy food along with Ethiopia's large diaspora in cities like Washington has put teff flour in the spotlight. Teff flour can also be used to make any flour-based food such as bread, pasta, tortillas and cookies.

Mama Fresh has also eager customers in Europe. The company flies injera to Sweden three times a week, to Norway twice a week and to Germany three times a month, with demand increasing by about 10 percent every month, Tessema said. "Predominately it's Europeans buying teff bread; those who cannot eat wheat or who are heath conscious," said Sophie Kebede, owner of Tobia Teff, a UK-based business firm specializing in the grain. "When we started in 2007 nobody knew when we said teff whether it was a Christmas pudding or a banana split, but I'm very happy to say we've come a long way from that now," Kebede said. "It's not yet a household name but at least many people know what teff is."

A mixture of teff flour and water is used to make injera

Protecting teff for the masses

Kebede gets her teff from farms located in southern Mediterranean countries. This is due to the Ethiopian Ministry of Trade strategically restricting exports of its increasingly sought-after grain to protect the country's food security.

Evidence would suggest the government has a right to proceed cautiously, because teff's global debut comes after a super grain quinoa hit a global market, rising consumption in more affluent countries. This made quinoa too costly for some locals in the countries growing it. "The government has to cover the daily consumption of its own people before it exports outside, which I can appreciate," Kebede said. "But at the same time it is much better for us if we can get teff from an Ethiopian farmer, because who is better than an Ethiopian farmer when it comes to teff."

Teff flour can also be used to make bread, pasta, tortillas and cookies

The consensus among those involved in the teff industry appears to be that the ban will eventually be lifted, although when and how the government goes about it will require significant coordination. "Obviously you've got the risk of driving up domestic prices of teff, and nobody wants that at all", said an American Matthew Davis, a partner at Renew Strategies, an early stage venture capital company based in Addis Ababa investing in Mama Fresh's plans. "So I think the government is going to be very cautious about that, and the way they're going to control that is by giving licenses to a select, controlled number of companies or exporters."

Davis notes that already much teff is leaving the country illegally across borders to Djibouti, Somalia and beyond to the West. "If it's going to happen, you might as well control it and get some tax revenue from it, and everybody's happy."

Wrestling with demand

Despite all the praise for teff's amazing nutritional properties it does have an Achilles heel. Due to teff previously being limited to growing in Ethiopia, it hasn't benefited from international agricultural research. Consequently, Ethiopian farmers haven't had access to modern farming methods or techniques available to other crops.

Such constraints have kept the crop's yields low and unable to keep pace with Ethiopia's increasing population, thereby driving the price of the grain beyond many Ethiopian families. The Ethiopian Agricultural Transformation Agency is focused on increasing teff production to at least match domestic demand, after which exporting it should be more palatable. "The opportunity this presents to the country is significant and the benefit over the long term will far outweigh the risks", Davis said, while noting the industry would have to commercialize and professionalize to export effectively, and take measures not to undermine the local market.

Hailu Tessema (right), founder of Mama Fresh, Ethiopia's first large-scale factory producing teff-based products

During the teff harvest, oxen are still used to stamp teff seeds out of the grass, followed by pitch forks to winnow. That hipsters in New York and Amsterdam are suddenly after a teff fix, might well perplex some of those 6.3 million Ethiopian farmers producing it.

Those at the forefront of teff's global march, such as Hailu Tessema at Mama Fresh, appear content with the current trajectory. "I'm very happy, Ethiopia is the founder of teff, so like coffee our teff is becoming important all over the world," Tessema said. 

Originally published in Story 1: AFP Bulletin and Story 2: DW.com