Lab in UB’s Clinical and Translational Research Center is one of few in the world studying an increasingly prevalent bacterium, once considered harmless
Children’s ear infections cause more than pain and sleepless nights; they temporarily disrupt hearing when children are at a critical age for speech and language development. They also have major social and economic costs.
But while infants and children receive immunizations against infections caused by Haemophilus influenzae and pneumococcus, there is no vaccine against Moraxella catarrhalis, an increasingly prevalent bacterium that causes at least ten percent of otitis media cases.
Now, University at Buffalo scientists, among just a handful of researchers in the world studying this organism, have received a $1.5 million National Institutes of Health (NIH) grant to develop a vaccine against it. The researchers are among the first tenants in UB’s Clinical and Translational Research Center, which opened in September on the Buffalo Niagara Medical Campus.
The goal of the current research, funded by the NIH’s National Institute on Deafness and Other Communication Disorders, is to identify new virulence mechanisms for this understudied pathogen, identify the structure of a candidate antigen for a new vaccine and develop a new vaccine.
According to Timothy F. Murphy, MD, SUNY Distinguished Professor of Medicine and Microbiology in the UB School of Medicine and Biomedical Sciences and principal investigator on the NIH grant, research on M. catarrhalis has lagged because it was originally believed to be a “commensal” or harmless bacterium. While it does cause milder cases of middle ear infections (otitis media) than other bacteria, Murphy said it is becoming more prevalent. Preliminary evidence also shows that existing ear infection vaccines are changing colonization patterns among otitis media pathogens, possibly increasing the prevalence of M. catarrhalis infections.
“Of the 15 to 20 million cases of otitis media each year in the U.S., about ten percent are recurring, causing incredible disruption for the child and the family,” explains Murphy. “When a child has the infection, the middle ear fills with fluid, a condition that can last for a month or longer. During that time, the child’s hearing is muffled, which disrupts the normal development of language and speech skills, potentially resulting in long term delays and learning problems in school.”
Recurrent ear infections also require repeated courses of antibiotics, which then contribute to the global problem of antibiotic resistance. Some children must undergo insertion of drainage tubes under general anesthesia.
“The best option would be to prevent these infections in the first place,” says Murphy.
The goal of the UB researchers is to identify M. catarrhalis antigens that are very similar among all strains so that a vaccine based on a single antigen will protect against as many strains of the bacterium as possible.
“Based on our results thus far, it looks like we will be able to identify antigens that are identical or very similar among all strains and genetic lineages,” says Murphy.
He and his colleagues are using bioinformatics to identify genes predicted to encode proteins on the surface of the organism, construct a gene chip to test which of more than 300 possible genes on the surface are identical or similar among multiple strains and then clone genes for some of the predicted proteins for testing in in vitro and mouse models.
The UB group is now testing several promising vaccine antigens that they have identified. A new vaccine could be ready for human testing in three to five years.
Murphy and his colleagues at UB are global leaders in the study of M. catarrhalis in otitis media in children and chronic obstructive pulmonary disease (COPD) exacerbations in adults. Their hope is that the same vaccine could be used to prevent both kinds of infections.
In addition to directing the M. catarrhalis research, Murphy directs UB’s Clinical and Translational Research Center and is senior associate dean for clinical and translational research in the UB medical school. For more than a decade, Murphy has studied how M. catarrhalis causes both otitis media in children and infections in chronic obstructive COPD in adults.
Ellen Goldbaum (UB); goldbaum@buffalo.edu; 716.645.4605