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Treating infections

Treating infections a vaccine has been developed that can prevent urinary tract infections ( utis), one of the most common health problems all over the world. The ailment is mostly caused by bacteria called E coli. Millions of people, especially women, have to be hospitalised for treatment of uti s and four times as many have to visit doctors. About 50 per cent of women in India contract such an infection at least once in their lifetime, and many of them are not even aware of it. Several cases go unreported, especially in rural areas.

Mostly, uti s are not life threatening and can be controlled by standard antibiotic therapy. However, if the infection is allowed to persist due to ignorance or indifference, which happens very often with Indian women, it can travel to the upper tract, infecting the kidneys and resulting in their failure.According to S C Chhabra, a nephrologist in Delhi, about 2,000 new patients report to hospitals every year requiring dialysis following damage to kidneys due to uti. Of these, a considerable number can avoid the trauma if they take care and control the uti at an initial stage.

A team of researchers led Solomon Langermann from MedImmune, a Maryland-based biotech company, in association with Washington Univer-sity, St Louis, have reported the development of a genetically engineered vaccine that can prevent uti. Initial studies in mice have been successful and the preliminary clinical trials have also shown great promise ( Science , Vol 276, No 5313).

The vaccine uses a new delivery method: a vaginal suppository (a pellet that is placed in the vagina and releases the medication slowly). Unlike the earlier injectable vaccines, this concoction of killed microorganisms triggers the production of a class of antibodies known as secretary iga that circulate in the mucosal surfaces. These block invading microbes present in the lining of the urinary and reproductive tracts like E coli. The vaccine formulation was injected into laboratory mice that were exposed to the microbes seven weeks later. The vaccinated mice were able to ward off uti for over seven months as some of the ig a antibodies leaked into the mucosal lining of the bladder and urinary tract.

In a trial just concluded which had 25 women, the vaccine was found to be effective, although not as much as the researchers anticipated. Women prone to utis acquired it less frequently and no side effects were noticed. But the effect of the vaccine diminished earlier than expected. It would appear that unless the efficacy is improved, vaccination would be required once every few months.

The earlier injectable vaccine called Urovac failed in 1980s. Inflammation at the site of injection, short lived protection and side effects were to blame. But the new vaccine targets only a single key protein called Filamentous h or Fim h , present on E coli . The bacteria deploy Fim h on the end of their long strands that extend from the cell body and latch onto sugar molecules on the surface of the host cells. Blocking this adhesive action can effectively prevent infection.

Vaccines based on this principle (developed for diseases like gonorrhoea caused by germs that use similar mechanisms as E coli ) have not fared well in the past. When the genetically engineered bacteria are coaxed into producing the large amount of adhesion proteins needed for a vaccine, the protein often become degraded or clumped together, losing their ability to provoke immune cells into making antibodies.

The MedImmune-Washington University team overcame this problem by genetically engineering E coli to express extra Fim h which they collected and purified. They were also able to modify the genome of the bacteria to express what is called chaperone proteins, which ensure that the Fim h fold into their proper formation as they were made. This method could well pave the way for developing a host of other vaccines for diseases like otitis media (inflammation of the ear), pneumonia, meningitis and gonorrhoea.

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