U.S. funding for AIDS vaccine research is tightening, the government’s top HIV expert warned Monday, even as he said scientists still must overcome a big hurdle in the hunt: how to harness the body’s first defenders to repel infection.

Today’s leading vaccine candidates can’t do that, noted Dr. Anthony Fauci of the National Institutes of Health. They work on a different pathway, one of cell-based immunity.

Indeed, scientists are approaching a critical crossroads where they must determine if that cellular approach alone will prove protective enough, said Seth Berkley, president of the International AIDS Vaccine Initiative.

“If cellular immunity turns out to be quite positive, we’ve got a series of candidate vaccines,” Berkley said at a meeting of the American Association for the Advancement of Science. “If it turns out that cellular immunity is not very useful ... it’s a much longer time period” to a useful vaccine.

That question looms just as researchers face tough new battles for U.S. funding.

After years of record budget increases in the 1990s, the NIH next year expects its total budget to increase just half a percent.

Fauci, head of NIH’s National Institute of Allergy and Infectious Diseases, didn’t say how much of that allocation is expected for research into an AIDS vaccine, although he said it remained a top priority.

Of the $600 million to $700 million invested in AIDS vaccine research worldwide last year, the United States provided $582 million, Fauci said - the vast bulk from the NIH.

The leveling off of government money means that NIH will more closely scrutinize all the research it funds, and that projects almost automatically renewed in earlier “years of largesse” now “don’t have the inside track,” he said.

Included on that list is a controversial study in Thailand that critics have attacked because 16,000 volunteers are receiving two vaccines that failed to work in previous testing. NIH has said that study should continue because no one knows if the two together might work. But Fauci said the project is being monitored closely and “there is no guarantee it is going to go all the way.”

“Our belt is being tightened for us,” he said, urging researchers around the world to better collaborate to avoid expensive duplicative efforts and speed their work.

The field of AIDS vaccines has been a roller coaster of scientific optimism and despair. About a dozen companies and organizations worldwide are attempting to develop one. The longtime lead candidate was deemed unsuccessful in 2000 after reaching final stage, or Phase III, testing.

Now, one developed by Merck & Co. is considered in the lead, with a Phase II study just beginning. Like many other AIDS vaccines under development, it is designed to spur so-called killer T cells to hunt down and destroy any cells newly infected with HIV.

The body does a pretty good job of that, Berkley noted. That’s why most HIV patients don’t become sick until years after they were infected - their own killer T cells work frantically to suppress infection.

If a cellular-based vaccine could improve that viral suppression, it would make a huge impact, he said - but no one knows yet. Preliminary data on Merck’s candidate is due in 2008.

Fauci said he doubts it will be that simple.

True HIV prevention likely will require generating a different immune-system component, “neutralizing antibodies,” to hunt down and eliminate the virus before it infiltrates cells, Fauci explained. That’s because HIV is notoriously tricky, able to hide in the body so well that a vaccine based on early killing of infected cells may not be enough, he said.

“I doubt very seriously whether we’ll have a successful candidate that will prevent infection until we’re able to induce neutralizing antibodies along with cellular immune responses,” Fauci said.

Many scientists now are hunting neutralizing antibodies against HIV. Five have been identified so far. Berkley said IAVI-funded researchers have just uncovered the structure of the strongest one identified yet, an important step in eventually creating ways to harness them for a vaccine.