READING NO. 5: Counterintuitive Cure: A nanovaccine that stops autoimmune disease by boosting the immune system

Counterintuitive Cure: A Nanovaccine That Stops Autoimmune Disease by Boosting the Immune System

A new treatment prevents type 1 diabetes in mice by turning the immune system on itself

The human body's immune system can quickly track down and kill cells that don't belong. Take certain kinds of bacteria: molecules on their surfaces flag them as foreign invaders, alerting the body's defenders to the breach and drawing a full-fledged attack on anything waving that molecular flag. But sometimes the system mistakenly attacks the body's own cells. The result is autoimmune disease, such as type 1 diabetes, in which the insulin-producing beta cells of the pancreas are attacked and destroyed by T cells.

Scientists have struggled to find ways to treat autoimmune disease without compromising overall immunity. Therapies that suppress the immune system carry the risk of letting infections and even tumors go unchecked. But researchers in Canada have found a way to prevent type 1 diabetes in mice by doing just the opposite—vaccinating to boost the immune system.

The approach, published April 8 in Immunity, exploits the immune system's built-in safety mechanism—a group of regulatory T cells whose job is to squelch overactive immune responses.

"Essentially, there is an internal tug-of-war between aggressive T cells that want to cause [an autoimmune response] and weaker T cells that want to stop it from occurring," says study senior author Pere Santamaria from the Julia McFarlane Diabetes Research Center at the University of Calgary in Alberta. Although they have seemingly opposite effects, these different classes of T cells are "musicians in the same orchestra," Santamaria explains. And they take directions from the same conductor—the antigen-presenting cell (APC).

APCs are specialized white blood cells that grab tiny bits of protein off the surfaces of other cells (like invaders or, in the case of diabetes, beta cells), chop them into pieces (antigens) and present them to T cells to instigate the immune response. "T cells have to be fed," Santamaria says. "If there is no antigen-presenting cell, there is no immune response."

When the aggressive, autoimmune disease-causing T cells are presented with antigens from dying beta cells, they keep attacking and killing the beta cells. But when the weak T cells that want to stop the disease are presented with those same antigens, they kill the APC. "A single weak T cell can blunt the problem by killing the orchestra leader," Santamaria says. And unlike aggressive T cells that die shortly after killing their targets, weak T cells proliferate. "They become long-living cells that attempt to regulate the disease," Santamaria says.

Santamaria designed a "vaccine" to boost the activity of the weak T cells. He used nanoparticles—spheres thousands of times smaller than a single cell—that were coated with beta cell antigens. In doing so, he created an APC doppelganger that could repeatedly activate the weak T cells, causing them to proliferate and kill the real APCs. The nanoparticles shield the antigens from degradation, meaning they stay in the system much longer, so they can be delivered at fewer intervals and at lower doses.

The nanovaccine prevented diabetes in a prediabetic mouse model and restored normal blood sugar levels in diabetic mice. Santamaria hopes to translate his exciting finding into human clinical trials. "We know what we want the compound to look like for use in humans—it's not a pie in the sky," he says. "But launching a clinical trial is not a trivial task. It requires that we do our homework properly."

Over 23 million people in the U.S. have diabetes, according to the most recent report jointly produced by the U.S. Centers for Disease Control, the National Institutes of Health (NIH) and the American Diabetes Association, although only 5 to 10 percent of those cases are thought to be autoimmune (type 1 diabetes). Type 1 diabetics have to carefully monitor their blood glucose levels and routinely administer insulin to keep them down. They have a heightened risk for kidney failure, heart and eye problems, and nerve disease.

Autoimmune disease affects up to 23.5 million Americans, according to the NIH, and it is one of the top 10 leading causes of death in female children and women in all age groups up to 64 years. Santamaria plans to test his approach in models of other autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. "We're trying to extend this paradigm to see if it applies to other autoimmune disorders, as well. We think it will but that remains to be seen. That’s our hope and dream."

VOCABULARY

track down sb/sth or track sb/sth down

to find someone or something after searching for them in many different places 
I'm trying to track down one of my old school friends.
They've finally managed to track down that book I wanted.

flag verb (MARK) 

/flæg/ (-gg-)

•

[T] to put a mark on something so it can be found easily among other similar things

Flag any files which might be useful later.

•

[T] specialized to mark computer information with one of two possible values so that you can process it later

We'll flag the records of interest in the database and then we can give you a print-out.

breach noun (OPENING) 

/briːtʃ/ [C]

formal a hole that is made in a wall or another structure used for protection during an attack

A cannon ball had made a breach in their castle walls. 

fully-fledged adjective 

/ˌfʊ.liˈfledʒd/ UK (US full-fledged)

completely developed or trained

What started as a small business is now a fully-fledged company.

After years of study, Tim is now a fully-fledged architect.

boost verb 

/buːst/ [T]

to improve or increase something

The theatre managed to boost its audiences by cutting ticket prices.

Share prices were boosted by reports of the President's recovery.

I tried to boost his ego (= make him feel more confident) by praising his cooking.

built-in adjective 

/ˌbɪltˈɪn/

If a place or piece of equipment has built-in objects, they are permanently connected and cannot be easily removed

All the rooms have built-in cupboards/wardrobes

squelch verb (STOP) 

/skweltʃ/

•

[T] US to quickly end something that is causing you problems

A spokeswoman at the White House has squelched rumors about the president's ill-health.

•

[T] US to silence someone by criticizing them

The senator thoroughly squelched the journalist who tried to interrupt him during his speech.

tug-of-war noun 

/ˌtʌg.əv ˈwɔːr//-ˈwɔːr/ [C usually singular]

a type of sport in which two teams show their strength by pulling against each other at the opposite ends of a rope, and each team tries to pull the other over a line on the ground

chop verb 

/tʃɒp//tʃɑːp/ [T] (-pp-)

•

to cut something into pieces with an axe, knife or other sharp instrument

He was chopping wood in the yard.

Add some fresh parsley, finely chopped.

Chop (up) the onions and carrots roughly.

informal Laura had her hair chopped (= cut) yesterday.

•

If something is chopped in finance or business, it is stopped or reduced

Because of lack of funding many long-term research projects are being chopped.

blunt verb 

/blʌnt/ [T]

•

to make something less sharp

•

to make a feeling less strong

My recent bad experience has rather blunted my enthusiasm for travel.

doppelgänger noun 

/ˈdɒp.əlˌgæŋ.ər //ˈdɑː.pəlˌgæŋ.ɚ/ [C]

a spirit that looks exactly like a living person, or a person who looks exactly like someone else but who is not related to them

a pie in the sky

A fanciful notion; ludicrous concept; the illusory promise of a desired outcome that is unlikely to happen

LISTENING COMPREHENSION

After closely reading the text, see how many questions you can answer correctly:

1) Enumerate the risks that are mentioned in the text as being associated with therapies that suppress the immune system

2) Say when and where this approach was published

3) Explain how regulatory T cells halt the immune system

4) How does the vaccine act?

5) How did the nanovaccine perform in both a prediabetic mouse model and in diabetic mice?

6) Which 3 organizations agree on the figure of 23 million people in the US with diabetes?

7) What percentage of this population is thought to be type 1 diabetes?

8) What other autoimmune diseases are planned to be tested following this same approach?