Crippled fungus acts as vaccine.

Even if your immune system can fend off harmful bacteria, viruses, and parasites, you still have fungi to fear. Worldwide, millions of people suffer debilitating and even fatal fungal infections. People with weakened immune systems, such as the elderly and AIDS patients, are particularly susceptible.

Despite this threat, there's not a single fungal vaccine available for human use, and microbiologists were for a long time pessimistic that there ever would be. Challenging that glum forecast, a research group has now used a genetically crippled form of the yeast Blastomyces dermatitidis to immunize mice.

While infections with this yeast are relatively rare in people, the advance lays the groundwork for similar vaccines against more common fungal threats, say researchers.

An inhabitant of soil, B. dermatitidis frequently infects dogs and can cause a fatal respiratory disease. The people facing the greatest risk of infection are outdoor enthusiasts, especially around the Great Lakes area.

Bruce S. Klein of the University of Wisconsin-Madison and his colleagues disabled the B. dermatitidis gene for a protein called WI-l, which helps the fungus attach to host tissue. Yeast unable to make WI-1 don't kill mice as normal strains do, Klein's team found.

The researchers then injected this live but harmless fungal strain into mice to trigger an immune response that could protect the animals from normal, deadly yeast. The strategy works, they report in the Dec. 1 JOURNAL OF CLINICAL INVESTIGATION.

In fact, the vaccine protected mice from several strains of B. dermatitidis, making it more practical for widespread use, says Dennis Dixon of the National Institute of Allergy and Infectious Disease in Bethesda, Md.

Fungal vaccines have trailed behind ones for bacteria and viruses because fungi are difficult to manipulate genetically. The challenge comes in part because they store their DNA inside a protective sac, the nucleus, just as human cells do.

Klein recently began testing the new vaccine in dogs. "Pet owners would indeed want to consider this prevention, given the cost of treatment and that it doesn't always work," Dixon says.

Last month, another research team reported disabling a key gene in Histoplasma capsulatum, the most common fungal cause of respiratory illness in people in the United States. Given Klein's success, this crippled fungus may serve as a vaccine as well, says Dixon.