Murphy leads fight agains ear infections
UB professor is developing a vaccine that would prevent common childhood ailment

By S. A. UNGER
Reporter Contributor

If you want to get the attention of parents with young children, just tell them that scientists are making significant strides toward developing a vaccine to prevent recurrent ear infections.

A leader in this endeavor is Timothy F. Murphy, professor of medicine and microbiology, whose research is currently funded by a five-year, $1 million grant from the National Institutes of Health (NIH).

The vaccine Murphy is developing targets a bacteria called nontypeable Haemophilus influenzae (NTHI), which not only is the second most common cause of ear infections (otitis media) in children, but also is a leading cause of recurrent infections in patients with chronic obstructive pulmonary disease, or COPD. A vaccine against NTHI is especially promising because it would be effective in both populations of patients.

"Otitis media and COPD are enormous national health problems in terms of human suffering and cost," says Murphy, whose work in this area has been funded by the NIH since 1983. "About 80 percent of children have a least one episode of otitis media by age three, and it is the most common reason for visits to pediatricians. Recurrent otitis media is painful and because it impairs hearing, it is associated with delays in speech and language development, as well as with learning problems in children as they reach school age."

Murphy adds that COPD, which includes chronic bronchitis and emphysema, is the fourth leading cause of death in the United States, with infections being the most common single identifiable cause of these deaths.

In order for a vaccine to be effective against recurrent ear infections, it must work within the first months of a child's life, according to Murphy. This is because if a child's throat becomes colonized with NTHI during his first year of life-even in the absence of an ear infection-he may then be prone to ear infections throughout childhood.

"Some vaccines do not induce an immune response in children under age two," he explains. "It will be critical to develop a vaccine for ear infections that is effective in infancy because it will be important to immunize early to prevent recurrent infections, which are the real problem."

To that end, Murphy's work focuses on two proteins on the outer membrane surface of NTHI-P2 and P6-each of which has the appealing feature of being able to generate antibodies in infants.

"P2 makes up 50 percent of the protein content of the outer membrane and is an immunodominant protein, which means it induces the human host to make antibodies to it," says Murphy.

The other protein he is focusing on in tandem with P2 is P6. Since discovering this protein 15 years ago, Murphy has learned much about it, including the fact that it is antigenically conserved; in other words, it is identical in amino acid sequence from strain to strain. In addition, he has made other discoveries that suggest that P6 would make a good vaccine antigen.

"What my lab has done is identify and characterize vaccine antigens and perform initial studies supporting the potential viability of the vaccine; it's up to the pharmaceutical companies to produce large amounts of the vaccine antigen for testing, which is now happening," says Murphy, who holds multiple patents on the P6 molecule pertaining to its gene and protein sequences and purification and diagnostic methods.

Currently, Murphy is dedicating his research efforts to continuing to learn as much as possible about the P6 molecule and the human response to it. "In particular, I want to know what parts of the molecule they [vaccinated individuals] are making antibodies to. Recently, we've done a lot of work on the antigenic structure of the P6 molecule, looking at how this protein is arranged in the outer membrane. Now we want to identify the specific parts of the molecule that are protective.