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Immunology

Against asthma

Proteins from the worm that causes schistomiasis may help control inflammation of the respiratory tract

eduardo cesarSchistosoma mansoni: raw material for a possible vaccineeduardo cesar

Like a skilful swindler the parasite that causes schistomiasis – the Schistosoma mansoni flatworm – easily dribbles its way past the defenses of the human organism and fixes itself to the wall of blood vessels in the intestine. Some of its eggs settle in the liver causing this organ to swell and this leaves 5% of its 200 million victims with a stomach that’s swollen like a soccer ball. After analyzing the changes in the immune system triggered by the schistomiasis agent, immunologists from Minas Gerais and Bahia are now trying to take advantage of a strategy that is similar to that of the parasite’s,  to lessen the discomfort caused by asthma, the chronic inflammation of the airways and lungs caused by an over-reaction of the immune system to proteins from mites found in dust and smoke, or even to medication.

The answer, imagined by Maria Ilma Araújo and Edgar Marcelino Carvalho, from the Federal University of Bahia (UFBA), is apparently simple. They are looking to unleash in the organism the same type of immunological reaction caused by the Schistosoma mansoni (except without causing the sickness), which is the same principle as the way vaccines work. They are hoping to achieve this objective using some of the proteins they collect from the surface of the parasite and they were identified and produced in a laboratory by teams from the Federal University of Minas Gerais (UFMG).

The team from Bahia has good reason to want to imitate the action of this parasite. A few years ago Maria Ilma and Carvalho noticed an intriguing effect among asthma sufferers in a small fishing village on the coast of north Bahia. Some of them had many less severe symptoms of this inflammatory disease than normal (over the last twenty years or so this sickness has become more common in the West and affects between 150 million and 300 million people worldwide, making the simple act of breathing real torture). Investigating what was different with these fishermen, Maria Ilma came up against an initially contradictory fact: those who had the mildest form of asthma were not necessarily the healthiest. In fact many of them were infested with worms like Schistosoma mansoni, common in communities like Vila Conde, where mains water and sewage disposal are still a luxury.

Given this result Manoel Medeiros Junior from Maria Ilma’s team monitored the health of asthma sufferers from three regions in Bahia for a whole year; schistomiasis is endemic in one of the regions and practically non-existent in the two others. The data, published in 2003 in the Journal of Allergy and Clinical Immunology, confirmed that asthma was less severe in those who were also contaminated with the parasite. Just one year later Maria Ilma found the explanation for the apparent paradox: as a response to infestation by Schistosoma mansoni, the immune system increases production of a defense system molecule called interleukin-10 (IL-10), which has an anti-inflammatory action and reduces the production of other molecules that exacerbate the inflammation, like three other interleukins (IL-4, IL-5 and IL-13). Described by Maria Ilma and her PhD students, Luciana Cardoso and Ricardo Oliveira in a series of articles published over the last few years,  this same mechanism, which possibly guarantees the survival of the parasite in the body, seems capable of reducing the asphyxia caused by asthma.

On noting that Schistosoma mansoni could contribute to fighting asthma, Maria Ilma contacted immunologists, Sergio Costa Oliveira and Alfredo Goes, from UFMG, who were working on developing a vaccine against schistomiasis and, like the group from Bahia, belonged to the Institute of Investigation into Immunology, one of the Millennium Institutes’ projects, financed by the Ministry of Science and Technology. Goes and Oliveira had already identified some proteins from the Schistosoma mansoni worm and were beginning to produce them in the laboratory, using Escherichia coli bacteria. Out of almost ten proteins, the team from Minas identified four that were capable of simulating the effects that Schistosoma mansoni causes in the organism and were candidates for inclusion in a vaccine against schistomiasis. According to an article published last year in Clinical and Experimental Immunology, the number of parasites fell by half in guinea pigs that received an experimental version of the vaccine containing the Sm29 protein. “In partnership with a team from Australia, we’re working on producing a vaccine containing a further two proteins. We expect to be able to lower even further the number of parasites in the organism”, says Oliveira.

This combination also seems to work against asthma. Recently Luciana Cardoso tested these proteins, known as antigens because they activate the immune response, in a test-tube. Both Sm29 and Sm22.6 stimulated the defense cells taken from the blood of asthma sufferers to produce interleukin-10, an anti-inflammatory substance, and inhibit the production of the molecules that worsen the respiratory inflammation. A similar effect was observed when proteins from Schistosoma mansoni were injected into guinea pigs suffering with symptoms similar to those of asthma, as indicated by a study to be shortly published by the team from UFBA and UFMG.

The results obtained so far indicate that the teams from Minas and Bahia have in their hands molecules that are candidates to form part of a double-action vaccine, capable of combating both asthma and schistomiasis. If confirmed this could be a more efficient and long-lasting alternative solution to the traditional steroid-based therapies (inhalable, orally administered or injectable) that are used to treat or prevent the shortness of breath crises caused by asthma. “We’ve just taken the first step”, says Luciana.

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