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Dr. Louis

Picker, a vaccine expert at Oregon Health & Science University, has shaken up the long, frustrating search for an AIDS vaccine. His latest study, published in Nature last week, has scientists scratching their heads, wondering if it might open up a new avenue for research.

Picker tested his vaccine in 16 monkeys who were then infected with simian immunodeficiency virus (SIV), a close relative of HIV, which normally would have sent them spiraling rapidly down to a miserable death. The experimental vaccine protected only nine of them, but it also did something never seen before: These monkeys slowly “cleared” the virus and now appear to be cured.

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“Three years later, you can’t tell them from other monkeys,” Picker said.

Dr. Anthony Fauci, the head of the National Institute for Allergy and Infectious Diseases, said the effect was “unique.”

And Dr. Barton Haynes, the director of the Human Vaccine Institute at Duke University’s medical school, said it was “potentially extremely important to understand how this happened.”

Scientists often test ideas for potential AIDS vaccines by creating similar ones against SIV. Never before has one eliminated an existing infection. In that sense, the effect of Picker’s vaccine was less like that of a measles or flu shot and more like that of the AIDS cures used in two famous cases, known as the Berlin patient and the Mississippi baby.

The Berlin patient, Timothy Ray Brown, was infected with HIV and cured only by obliterating his immune system to defeat his leukemia, and then injecting bone marrow from a donor with a rare HIV-blocking mutation. The unidentified baby was born to an infected mother in Mississippi and apparently infected with HIV, but then cured with early and large doses of antiretroviral drugs.

Both now appear to have no HIV lurking deep in their bodies, but it is impossible to be sure because not every bit of their tissue can be tested.

Making vaccines by simply weakening the virus that causes AIDS has failed because the virus mutates a hundred times faster than even the fast-mutating flu virus. In Picker’s vaccine, SIV genes are fused to those of another virus, the cytomegalovirus. (In the herpes family but different from its relatives that cause lip and genital sores, chickenpox and shingles.)

HIV fusion has been tried with adenoviruses and others, but cytomegalovirus seems to work better. It’s not entirely clear why, but one theory is that cytomegalovirus has a very long history of infecting primates — so much so that 100 percent of monkeys and about 80 percent of humans get it in their lifetimes.

Therefore, we primates have adapted to it. Although the virus can be lethal to fetuses and to those with immune systems suppressed by AIDS or transplant drugs, in most victims it causes no symptoms.

As in any infection, the thymus gland generates new white blood cells called T cells — in this case, CD8 hunter-killer cells — primed to target the specific virus. But in the case of Picker’s vaccine, those cells stay in an unusual “half-alert” state. A full-blown immune response eventually exhausts itself, and can even be dangerous.
Unactivated CD8s wander around aimlessly, while fully activated ones behave like storm troopers.

But the half-activated CD8s persist in tissues, eliminating their targets quietly without triggering inflammation or even a mild fever.

When SIV genes are fused to the cytomegalovirus spine, the CD8s kill SIV-infected cells too.

Since it protected only some monkeys, the new technique might be best used in combination approaches. For example, Fauci said, it could be given with a vaccine that generates antibodies against HIV “and maybe eliminate the cells that sneak past the antibody shield.”

Alternatively, the vaccine might be given to infected patients who are on antiretroviral drugs to see if it can “mop up” lingering reservoirs of virus.

It should take up to three years to get a human version ready for trials, Picker estimated.

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