WASHINGTON - A century after history's worst flu pandemic, scientists are hunting for a super-shot for the next super-flu.

Stronger vaccines could guard against the next pandemic and ordinary winter influenza at the same time.

That's a tall order.

Flu viruses constantly mutate just enough to beat our best defenses. That's why doctors recommend getting the vaccine every year. But if a never-before-seen flu strain were to cause another pandemic, those annual shots wouldn't help.

Among the new strategies: Researchers are dissecting the cloak that disguises influenza as it sneaks past the immune system, and finding some rare targets that stay the same from strain to strain, year to year.

"We've made some serious inroads into understanding how we can better protect ourselves. Now we have to put that into fruition," said well-known flu biologist Ian Wilson of The Scripps Research Institute in La Jolla, California.

The new focus is a universal flu vaccine that could protect against most strains of the virus.

Labs around the country have research underway. If it pans out, it might eventually replace the annual fall shot in favor of one every few years - or maybe even a one-time childhood dose.

The misnamed Spanish flu infected one-third of the global population and killed at least 50 million people, including 675,000 Americans, by 1919. Historians think it started in Kansas in early 1918.

Three more flu pandemics have struck since, in 1957, 1968 and 2009, spreading widely but nowhere near as deadly.