Body's anti-HIV 'training manual' offers vaccine hopes

The body's own "training manual" for successfully attacking HIV has been recorded by scientists and it is hoped it can be used to design vaccines.

HIV mutates to survive the onslaught of a patient's immune system.

However, some patients develop highly effective antibodies that can neutralise huge swathes of HIV mutants.

An analysis of the arms race between body and virus, published in the journal Nature, has shown how these antibodies are made.

When someone is infected with HIV, their body produces antibodies to attack it. But the virus mutates and evades the offensive, so the body produces new antibodies that the virus then evades and the war goes on.

However, after about four years of this struggle some patients hit on to a winner by targeting something the virus finds harder to change - an Achilles heel.

Barton Haynes

"Even though the virus mutates and there are literally millions of quasi-species of virus because of all these mutations, but there are parts the virus can't change otherwise the virus cannot infect - these are the vulnerable sites," Prof Barton Haynes, of Duke University, in North Carolina, reported.

At this stage of the infection it is far too late to make a difference for the patient as the virus is hiding in untouchable reservoirs.

However, some researchers believe that vaccines that encourage the body to produce these "broadly neutralising antibodies" may give people immunity to the virus.

The research team's study is based on a patient in Africa who had a rapid diagnosis, about four weeks after being infected with the virus.

They were eventually able to produce an antibody named CH103 that could neutralise 55% of HIV samples.

It was not produced in one easy step. Rather it was the product of the war of the immune system and HIV trying to out-evolve each other.

However, through regular genetic analyses of both the immune system and virus, researchers could piece together each of the steps that culminated in the production of CH103.

It is like a training manual for the immune system.

Prof Haynes said: "What we were able to do was map out the arms race of both virus and antibody, and in doing so we have now a map.

"This is the first time we've been able to see the actual road map."

He said the challenge now was to see if re-creating those steps could lead to a viable vaccine.

Jane Anderson

However, he said it would almost certainly need to be a vaccine combining multiple "Achilles heels" - in the same way that HIV therapies are a combination of drug treatments.

Prof Jane Anderson, consultant at Homerton hospital in London and chair of the British HIV Association, said: "The study gives important insights into the ways in which the human immune system responds to HIV infection and increases our understanding about the relationships between the virus and the human host.

"This is another welcome step on the path to develop vaccines against HIV."

Sarah Joseph

Dr Sarah Joseph, who tests HIV vaccines at the Medical Research Council clinical trials unit, said: "This paper is really interesting. Some people do make antibodies that neutralise a lot of HIV virus, bit it is not of use to them as they produce it way too late."

She said harnessing these antibodies "could be a big deal" and there was "even talk about mass-producing antibodies and infusing people with them".

New way to treat CDI and other common hospital-acquired infection

The right image shows abundant S-nitrosylation (green) in human colitis compared with much less found in the left image of a normal colon. (Credit: UCLA/University of Texas Medical Branch at Galveston)

Researchers at the David Geffen School of Medicine at UCLA and the University of Texas Medical Branch at Galveston have discovered a molecular process by which the body can defend against the effects of Clostridium difficile infection (CDI), pointing the way to a promising new approach for treating an intestinal disease that has become more common, more severe and harder to cure in recent years.

In the U.S., several million people are infected each year, approximately double the incidence of a decade ago, mainly due to the emergence of a new, highly virulent strain of the bacteria that causes CDI.

As a result of the study findings, published in the Aug. 21 online edition of the journal Nature Medicine, the researchers are preparing to launch clinical trials using their discovery as a new CDI therapeutic approach.

The team also included researchers from Case Western Reserve University, Tufts University and the Commonwealth Medical College.

CDI is a bacterial infection that can cause diarrhea and more serious intestinal conditions, such as colitis, the inflammation of the colon. In the most severe cases, CDI can be fatal. It is most commonly acquired in hospitals by patients, particularly the elderly, who are being treated with antibiotics for another infection.

Currently, one of two potent antibiotics is used to treat the infection, but up to 20 percent of patients experience a relapse and a return of symptoms within a few weeks.

"We are treating a disease caused by antibiotics with yet another antibiotic, which creates the conditions for re-infection from the same bacteria," said study co-author Dr. Charalabos Pothoulakis, director of UCLA's Inflammatory Bowel Disease Center and a professor of medicine in the division of digestive diseases. "Identification of new treatment modalities to treat this infection would be a major advance."

Clostridium difficile causes diarrhea and colitis by releasing two potent toxins into the gut lumen that bind to intestinal epithelial cells, initiating an inflammatory response. These toxins are released only when the Clostridium difficile bacteria are multiplying. When antibiotics are used to treat another infection, it changes the bacterial landscape in the gut and, in the process, may kill bacteria that under normal conditions would compete with Clostridium difficile for energy. Scientists believe this may be what provides the opportunity for Clostridium difficile to grow and release its toxins.

The UCLA and University of Texas researchers found in laboratory studies that upon infection with Clostridium difficile, human cells in the gut are capable of releasing molecules that will neutralize these toxins, rendering them harmless. In animal studies, the researchers showed that using a drug to induce this process, known as protein s-nitrosylation, inhibited Clostridium difficile toxins from destroying intestinal cells. Forthcoming clinical trials will test this approach in humans.

"Our study suggests a novel therapeutic approach for treating Clostridium difficile infection by exploiting a newly discovered defense mechanism that has evolved in humans to inactivate microbial toxins," said Tor C. Savidge, an associate professor in the division of gastroenterology and hepatology at the University of Texas Medical Branch at Galveston and the paper's lead author.

Along with its potential to provide a much-needed new approach to treating CDI, the discovery could be applied to developing new treatments for other forms of diarrhea, as well as non-diarrheal diseases caused by bacteria.

This Blog May Contain Nuts! Allergic Reactions

There is a big difference between eating well and eating healthily.

There is an even bigger difference between a minor intolerance to food and a full blown allergy.

If you do have a real food allergy, then take heart, more and more research is taking place on the subject and an interesting picture is emerging.

Labeling

Better food labeling is thought to help but it also sometimes confuses and deceives. Independent tests on labeled and unlabeled foods showed an alarming inconsistency between the contents and the information on the label. Dangerously so, in some cases.

Litigation

This misinformation on labels is often prompted by the fear of litigation. So, the suppliers adopt a 'better safe than sorry' mentality, which is not at all helpful for consumers.

Anaphylaxic Shock

Even if the food industry does find a better way to label foods, there will always be the danger of an accidental exposure to high concentrations of an allergen. "The main risk is from caterers and restaurants," says Frans Timmermans of the Netherlands Anaphylaxis Network.

"In the UK most deaths are from curries, weddings, parties, and not knowing what ingredients are in satay and pesto. Otherwise, it's often down to not knowing that you are allergic in the first place." The first time you discover it can be a shock.

More People are Allergic to Hazelnuts than Peanuts

A Passing Exposure

Some people with a severe food allergy are afraid of even a passing exposure to an allergen, and this has led some to ask for bans of potentially dangerous foods in public areas such as schools, to reduce the risk.

Some American high schools, for example, are now banning food products containing peanuts. In one instance, a school bus was evacuated and then taken out of service to be decontaminated after a single peanut escaped from its wrapper. "People in favour of various bans feel it is just easier to have the food eliminated," says Scott Sicherer, an allergist at the Mount Sinai School of Medicine in New York City.

Proportionate Response

Others believe that such measures are out of proportion to the real danger. Writing in the medical journal BMJ last year, medical sociologist Nicholas Christakis of Harvard Medical School in Boston observed that efforts by US schools to prevent students being exposed to peanuts "represent a gross overreaction to the magnitude of the threat" (BMJ, vol 337, p 1384).

According to Timmermans, parents can sometimes become so worried about the possible threat to their children that they cause the children themselves psychological distress.

Timmermans says his daughter, who is also highly allergic to peanuts, would be able to sit next to someone eating a peanut dish without experiencing a reaction. Although he admits, it would make her very uneasy.

How to test for allergies

There are three main or approved methods to test for an allergic reaction and these should be done under strict medical supervision:

• The skin-prick test: A drop of a solution containing the suspected allergen is placed on the skin of the subject's forearm, which is then pricked with a needle. A positive reaction is indicated by itchiness and a reddening of the skin, or a white swelling.
• Blood tests: High levels of allergen-specific antibodies in the blood indicate an allergy.
• Food challenges: Research teams from the EuroPrevall task force are using a chocolate dessert which can be spiked with an allergen without a noticeable change in flavour. Each team feeds its subjects increasing amounts of the dessert at 20-minute intervals, containing allergen doses ranging from 3 micrograms to 3 grams, until the subject reacts - for example with a skin rash or swelling. The placebo, identical except that it contains no allergen, is administered in the same way but on a different day.

What is a food allergy?

Our immune system is meant to protect the body from invading parasites, bacteria and other foreign substances. Sometimes it overreacts to what should be a perfectly innocuous food or other substance, causing an allergic reaction.

IgE Antibodies
Most people who suffer from a food allergy have immunoglobulin E (IgE) antibodies that are primed to respond to the allergen involved. In the presence of the allergen, the IgE antibodies activate mast cells around blood vessels and in the skin. Histamine released by these cells causes small blood vessels to dilate, giving rise to the well-known symptoms such as itching and swelling in the mouth, skin rash, itchy or runny nose or diarrhoea.

Severe Shock
The most dangerous result is anaphylaxis, a whole-body reaction which can end in a catastrophic fall in blood pressure combined with breathing difficulties, sometimes resulting in death.

Coeliac Disease
Not all food allergies are mediated by IgE. Perhaps the best known of this other group is coeliac disease, an allergy to proteins present in the gluten of wheat, barley and rye. It is caused by an overreaction by the immune system's T-cells, which damages the lining of the gut. Sufferers endure diarrhoea, loss of weight and potentially malnutrition.

Food Intolerance
True food allergies should not be confused with "food intolerances". Rather than being caused by an overenthusiastic immune system, milk intolerance, for example, results from a lack of the enzyme the body needs to break down lactose, the main sugar in milk. Symptoms include nausea, abdominal pain and, once again, diarrhoea.

Building your resistance

While the symptoms of an allergic reaction to foods can be treated, there is no accepted therapy to prevent the reactions in the first place.

There may be hope, for those with a peanut allergy at least. A team from Addenbrooke's Hospital in Cambridge, UK, recently exposed four children to a daily dose of peanut flour, starting with just 5 milligrams. This year they reported that by the end of the six-month trial the children were able to tolerate 10 whole peanuts a day (Allergy, vol 64, p 1218).

If you or a friend or family member have a peanut allergy, please do not try this at home. Always consult with your doctor or with a specialist before taking risks with your health.