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In mice, a step towards a vaccine for HIV

Tests on lab mice have opened up a new path towards a vaccine against HIV, one of the most frustrating quests in the 30-year history of AIDS, scientists reported on Wednesday.

Genetically modified mice fought back the human immunodeficiency virus

(HIV) after they had been injected with genes to make antibodies, the first line of defence in the immune system, the report said in the journal Nature.

First identified in 1981, AIDS has claimed at least 25 million lives, although the annual toll is falling sharply from the peak of the pandemic in response to drug treatment.

But AIDS campaigners say the pandemic will only be crushed once a vaccine emerges. So far, in clinical trials, only one candidate formula has had even a modest effect, providing a shield of only 31 percent against the risk of HIV infection.

This has prompted researchers to return to the drawing board, to look for "broadly neutralising antibodies" -- Y-shaped proteins that are the immune system's foot soldiers -- among the tiny number of people with an innate ability to resist HIV.

So far, this trawl has turned up around 20 so-called "bNAbs," but there are big unknowns as to how they work and, if so, whether they can be made into a deliverable vaccine.

Delving into this, a team led by David Baltimore at the California Institute of Technology (Caltech) says it has developed a way to deliver bNAb-making genes to lab mice.

The rodents were engineered to carry human cells that allow HIV to penetrate and reproduce.

The approach, called Vectored ImmunoProphylaxis, or VIP, entails using a harmless virus as a "Trojan horse" in which they tucked the genes able to turn out specific bNAbs.

They then injected the virus into the leg muscles of the mice, where it holed up in cells, enabling the bNAb genes to produce antibodies in response to HIV.

The mice were first challenged with just one nanogram of AIDS virus -- enough to infect most non-treated mice that received it -- but the dose was eventually cranked up to 125 nanograms without problems. There were no signs of any side effects.

"VIP has a similar effect to a vaccine but without ever calling on the immune system to do any of the work," said Alejandro Balazs, lead author of the study, in a press release issued by Caltech.

"Normally, you put an antigen or killed bacteria or something into the body, and the immune system figures out how to make an antibody against it.

We've taken that whole part out of the equation."

The team stressed that the jump from mice to humans is large.

"We're not promising that we've actually solved the human problem," said Baltimore. "But the evidence for prevention in these mice is very clear."

He added the team was drawing up plans to cautiously test the method in small-scale human clinical trials.

Baltimore co-won the 1975 Nobel Prize for Medicine at the age of 37 for his work on reverse transcriptase, a key enzyme in the reproduction of retroviruses

-- the family that includes HIV.

In an email exchange with AFP, he said VIP was "like gene therapy, but distinct."

Gene therapy entails slotting a gene into the patient's DNA that corrects a flawed, disease-causing counterpart.

Hopes for this field of research were clouded by several reverses, notably the death of a young volunteer, Jesse Gelsinger, in 1999.

The tragedy raised doubts about where genes should be inserted in the genome and about the safety of the virus that delivered them.

Baltimore explained that VIP used a small, harmless vector, an adeno-associated virus (AAV), which took up residence in the muscle cells but did not slot genes into the mouse's DNA code.

"It's not an 'insertion' but a free plasmid-like element that will exist in muscle cells," he said.

Publication of the study coincided with the eve of World AIDS Day.

The number of people living with HIV currently stands at about 34 million, according to the latest UN figures. (AFP)


<한글 기사>

HIV 감염차단 유전자요법 개발

에이즈를 일으키는 인간면역결핍바이러스(HIV) 의 감염을 막고 치료까지 가능한 유전자요법이 개발됐다.

미국 캘리포니아 공대(California Institute of Technology)의 데이비드 볼티모 어(David Baltimore) 박사는 HIV를 공격하는 인간항체 생산 유전자를 주입하면 HIV 감염을 100% 막을 수 있다는 사실이 쥐실험 결과 확인됐다고 밝힌 것으로 AP와 AFP 통신이 지난달 30일(현지시간) 보도했다.

그의 연구팀은 태어날 때부터 HIV에 대한 선천적 저항능력을 가지고 있는 소수의 사람들이 지니고 있는 이른바 광범위 중화항체(broadly neutralizing antibody)를 만드는 유전자를 무해한 바이러스에 실어 쥐의 다리 근육에 주입했다.

이 쥐들은 보통쥐가 아니라 유전자조작으로 인간면역세포를 갖게 된 쥐들이다.

그렇게 한 이유는 쥐의 면역세포는 HIV에 감염되지 않기 때문이다.

근육에 주입된 유전자는 쥐의 수명인 1년 이상 대량의 항체를 만들었고 아주 많은 양의 HIV가 주입됐는데도 면역세포가 감염되지 않았다. 또 아무런 부작용도 나타 나지 않았다.

이 유전자는 쥐의 다리근육 세포 안에 자리잡았지만 쥐의 DNA에는 들어가지 않았다. 볼티모어 박사는 유전자가 '삽입'된 것이 아니라 플라스미와 비슷한 자유소자로서 근육세포 안에 존재한다고 설명했다. 

그러나 이 쥐실험 결과가 사람에게서도 그대로 나타날지는 알 수 없다.

볼티모어 박사는 이 유전자요법에 대한 특허를 신청했으며 앞으로 몇 년 안에 임상시험을 시작할 계획이라고 밝혔다. 

뉴욕의 아인슈타인-몬트피오르 에이즈 연구소소장 해리스 골드스타인 박사는 이 것이 사람에게도 효과가 있는 것으로 확인된다면 HIV의 예방만이 아니라 치료도 가능하게 될 것이라고 논평했다.

과학자들은 지난 30년 동안 에이즈 예방백신을 개발하려고 노력했지만 2009년 면역효과가 30%에 불과한 백신을 만들어낸 것이 고작이다. 

볼티모어 박사는 37세 때인 1975년에 HIV가 포함된 레트로바이러스의 증식에 핵 심적인 역할을 하는 역전사효소에 관한 연구로 노벨의학상을 수상했다.

이 연구결과는 영국의 과학전문지 '네이처(Nature)' 온라인판에 발표되었다.