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Tuesday, February 2, 1999 Published at 15:17 GMT


Best hope HIV vaccine causes Aids

A macaque monkey died of Aids after being given the experimental vaccine

One of the greatest hopes for an HIV vaccine has suffered a serious, perhaps fatal, blow after having been shown to cause Aids in adult monkeys.

Dr Ruth Ruprecht explains why she believes live attenuated vaccines cannot be safe
Dr Ruth Ruprecht, of Harvard Medical School, led the research and told BBC News Online: "I think the current approach to attenuate Aids viruses to generate vaccine strains is doomed to failure."

Vaccines based on "live attenuated" viruses cripple HIV by deleting genes. A difficult balance has to be found - if it is too crippled the immune system will not respond and give protection, if it is not crippled enough it could cause disease.

Dr Ruprecht believes that HIV's method of reproduction lets the virus rapidly change its genetic make-up. It becomes stronger and stronger and eventually compensates for the deleted genes.

Dr Paul Johnson, of the New England Primate Research Centre, Massachusetts, comments on the work published in Nature Medicine and considers whether the new discovery is the "final nail in the coffin".

No alternative

He agrees that retroviruses like HIV have a "notorious propensity" to adapt their genetic structure but argues that there are currently no real alternatives to live attenuated HIV vaccines, a point Dr Ruprecht disputes.

Dr Johnson believes: "No other vaccine approach has been able to consistently generate sustained and broadly effective immunity.

"In the light of the continued spread of HIV-1, its expanding and devastating impact on the developing world and the current absence of a effective alternative vaccine, research on live attenuated vaccines needs to continue apace."

The primary concern about live attenuated vaccines has always been safety. Those fears have now been confirmed by Dr Ruprecht's team. They showed three years ago that new-born monkeys given these vaccines developed Aids, but that "left the door open for their use in adults," says Dr Ruprecht.

Monkey died of Aids

In the new study, sixteen adult macaque monkeys were given a vaccine with three crucial genes deleted. Within three to five years, one died of Aids, two developed early signs of disease and others had medical abnormalities which may have been caused by the vaccine, though no controls were included.

By the end of the study, the vaccine virus had been completely replaced in the monkeys by new mutated forms of HIV. The changes are "not controllable or predictable" says Dr Ruprecht.

She says: "The only way I can see a live attenuated vaccine being used against human Aids is if researchers can identify the particular genes which enable the virus to actually cause Aids - we in fact don't know yet where that capability of the virus lies."

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