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Vaccine Design Underway Against the Leading Cause of Childhood Hearing Loss


Tuesday, September 26, 2006 - Researchers are developing the first vaccine against the leading cause of childhood hearing loss. In a critical step toward a new vaccine, a team at the University of Rochester Medical Center has received $4 million in grants to determine why a bacterial ear infection called acute otitis media causes pain, fluid buildup and hearing loss in some children, but not in others. Based on recent breakthroughs and the pace of the work, researchers said preliminary clinical trials for a new vaccine could begin next year.

In the age of daycare, 83 percent of U.S. children experience one or more ear infections by age three. In some cases hearing loss becomes permanent. Even when temporary, month-long bouts of hearing loss can result in developmental setbacks, especially when several occur in a single year.

A bacterial strain called Nontypeable Haemophilus influenzae (NTHi) is the current leading cause of ear infections, including acute otitis media. Another pathogen, pneumococcal bacteria, was the principle cause of both otitis media and spinal meningitis in children until technology developed at the Medical Center led to the introduction in 2000 of the Prevnar vaccine. It caused the incidence of pneumococcal infection to decline dramatically, and NTHi emerged as the leading cause of ear infections starting in 2001. Thanks to the new grants, the same institution is now positioned to lead the drive toward an NTHi vaccine.

"Otitis media is the no. 1 reason that children receive antibiotic treatment following a doctor’s office visit, and we believe it can be prevented through vaccination,” said Michael Pichichero, M.D., professor of Microbiology, Immunology, Pediatrics, and Medicine at the Medical Center. “We expect to explain how some kids naturally protect themselves, and to package that protection for those who can’t,” said Pichichero, project leader for the new grants.

The speed with which a new vaccine is designed will depend on whether children’s ability to fight off otitis media is determined by immune cells in their ear mucus, or by cells circulating in their blood and lymph vessels, Pichichero said. If immune cells (antibodies) in the blood are most important, vaccine development will proceed rapidly because microbiologists have plenty of experience with vaccines delivered through the standard shot in the arm. If the solution lies with ear mucus antibodies, the team will need to create a new kind of vaccine science.
400 Infants

Investigators will examine the immune systems of 400 2-month-olds divided into three groups with different histories: no otitis media infections, few infections and many infections. By comparing patterns of immunity response between the groups, researchers expect to get a clear picture of how natural protection is achieved, and of what a vaccine will need to do to match it.

Recognizing, destroying and remembering foreign invaders are central responsibilities of the human immune system. Without causing an actual infection, vaccines introduce a weak version of a disease molecule to the system, which remembers it and is afterward primed should a natural version of the disease come along. Two types of immune system cells, T cells and antibodies, enable the system to “remember” bacteria, and will be watched closely during the current study.

Once researchers confirm the kind of immune response needed to achieve protection, they can choose for inclusion in the vaccine the bacterial proteins that make that happen. The human immune system reacts, not to the presence of a whole bacterial cell, but instead to specific proteins on the surface of the bacterium that reveal its identity as an invader. Past research has revealed four such NTHi surface proteins as excellent candidates for inclusion in a multi-component protein vaccine. The next step is to conduct human cell and preclinical experiments on the four to confirm that they induce protection and belong in a proposed vaccine.

An ideal vaccine would include four bacterial proteins, instead of one, to cut off a bacterial escape route. Bacteria reproduce and evolve (mutate) so rapidly that they can become unrecognizable to the immune system, even if strengthened by a single-protein vaccine. Based on the data collected and statistical analysis, researchers believe the multi-component vaccine will provide protection to the world population despite the tremendous variety in bacterial strains.

To complete the study, the team will need to collect more than 5,500 samples of blood and mucus from 400 infants from the time they are two months old through their second year. The endeavor will require singular pediatric expertise, including the ability to perform tympanocentesis, where a needle is used to puncture the baby’s eardrum and remove fluid. To meet this challenge, the Medical Center is partnering with Pichichero’s practice, the Elmwood Pediatric Group, a private practice in Rochester, N.Y. It has been part of pediatric clinical trials for 60 years, including those for the original polio vaccine, and has 20 years experience in otitis media studies.

The new funding is comprised of $3.5 million grant from National Institute of Deafness and Communication Disorders and $500,000 from the Thrasher Foundation. In addition to pediatric expertise, the team attributes the grant success to decades of vaccine design experience at the Medical Center, including the work with Haemophilus influenza type b (Hib), Prevnar (pneumococcal 7-valent conjugate vaccine), acellular pertussis vaccines, meningococcal vaccines and combination vaccines.

Accumulated expertise, funding and relationships have made the current project possible. For example, some preliminary work in this area was done at the Medical Center, and some elsewhere. Among the possible vaccine ingredients are bacterial proteins identified at other universities (e.g. Ohio State, University of Buffalo) and at pharma companies (e.g. GlaxoSmithKline).

“For researchers to share their work with a lead institution for the final design phase means they believe a vaccine will come out of this project,” said Barbara Iglewski, Ph.D., chair and professor of Microbiology & Immunology at the Medical Center. “Their trust, and the urgent needs of children, leave us with a real sense of mission.”


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