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By Paul Webster, Ph.D., Jose N. Fayad, M.D., and Ali Andalibi, Ph.D.
Otitis Media, middle ear infection, is the number one reason sick children visit the doctor. Obviously a vaccine would be highly beneficial to many children. Scientists are working on solutions but today’s research will likely benefit the next generation.
Bringing a vaccine to market can take many years. The first step is for scientists to identify antigens that can be targeted by the vaccine. Potential antigen targets are usually proteins on the organism to be vaccinated against. The proteins must be present on the organism during an infection and usually the protein must be present on the surface of the target organism.
Once the target antigens have been identified, clinical studies are established to test the efficacy of the vaccine. This usually means that large, random groups of patients are injected with antigens (or with a placebo) and the effect of the injection on the disease is determined by trained clinicians. Usually the patients, the people performing the injections and the clinicians evaluating the results of the clinical tests are not told whether an actual vaccine or a placebo is being used. These are called “blind” tests.
Obtaining sufficient numbers of patients on which to perform these trials can be difficult, especially for vaccines, where larger numbers are needed to screen for rare complications that might occur in response to antigen injection.
Once the clinical trials have been completed, and have proven successful, an application is then sent to the Food and Drug Administration (FDA) to obtain formal approval to use the target antigen as a vaccine. If the FDA approves, then the vaccine can be produced (a process that requires large amounts of antigen to be prepared and purified), bottled in an injectable form and distributed for use.
Though we are still in the process of developing a vaccine specifically for otitis media, other vaccines have been effective in reducing otitis media.
Pneumococcal Vaccines: The pneumococcal-CRM197 conjugate vaccine is now routinely used in infants and toddlers to prevent invasive pneumococcal disease. This vaccine is a mixture of seven purified pneumococcal capsular molecules taken from the seven different bacteria that cause 80 percent of invasive pneumococcal disease in children and approximately 60 percent of pneumococcal acute otitis media. All of the capsular molecules are coupled to a nontoxic carrier protein capable of eliciting a strong immune response. Other pneumococcal conjugate vaccines that are in development use capsule molecules from more bacteria and different carrier proteins. Pneumococcal proteins are also being tested for their ability to protect against pneumococcal bacteremia, pneumonia and otitis media.
Nontypeable H. influenzae (NTHi) and Moraxella catarrhalis Vaccines: In addition to its genetic diversity, NTHi has shown extensive sequence and antigenic variation among the gene products that interact with the human immune system, including the outer membrane proteins and secreted virulence factors. It does, however, have conserved antigens with vaccine potential and several of these have shown promise in animal studies.
The development of vaccines for the prevention of M. catarrhalis-mediated disease is of great importance due to the fact that most of the isolates of M. catarrhalis are resistant to penicillin. Antigens considered or tested to date include proteins involved in adhesion, nutrient acquisition, transferring binding proteins, outer membrane proteins and virulence factors.
Respiratory Virus Vaccines: In addition to vaccines against the above bacterial pathogens, efforts are also being made to develop vaccines against upper respiratory viruses including the influenza virus, parainfluenza virus and the respiratory syncytial virus.
A study more than 10 years ago showed that inactivated influenza A virus vaccine reduced the incidence of acute otitis media associated with influenza A by 83 percent and decreased the overall incidence of acute otitis by 36 percent. Results of another study done in the United States also showed that in comparison to control groups, vaccinated children had 32 percent fewer episodes of acute otitis media during the influenza season. Moreover, children vaccinated with an intranasally delivered live attenuated influenza virus vaccine had a 30 percent drop in episodes of acute otitis media where the patient had a fever, and the vaccine was shown to be 93 percent effective against culture-confirmed influenza.
Development of vaccines is not a trivial process. The initial research can take years to find suitable target antigens, the initial production of vaccines for the clinical trials requires an expensive batch facility, the clinical trials have to be designed and suitable patients have to be identified. Then FDA approval has to be obtained and large amounts of the vaccine, prepared in even larger production facilities must be produced, packaged and shipped. Nonetheless, as such successes as the polio and rubella vaccines have proved, vaccines are well worth the cost and effort and merit our support for research and development.
Paul Webster, Ph.D., is a scientist and head of the Ahmanson Advanced EM and Imaging Center at the House Ear Institute (HEI) in Los Angeles, Calif. He received his education in the United Kingdom (B.Sc. at Sheffield and Ph.D. at Brunel University in London) where his long-standing interest in finding out how pathogens affect cells and how cells counter attacks from pathogens was first stimulated. He has over 100 peer-reviewed publications on this subject. Hired by HEI from Yale University, where he ran a shared imaging facility, Dr. Webster has also lived and worked in Germany and Kenya.
Jose N. Fayad, M.D., is an associate at the House Clinic in Los Angeles, Calif. He received his medical degree from University Paul Sabatier in Toulouse, France, followed by residency at the University’s Hospital Purpan in Toulouse and a research fellowship at HEI in Los Angeles. Formerly on the faculty of the University of Southern California and the College of Physicians and Surgeons, Columbia University, N.Y., Dr. Fayad sits on the editorial review board of several peer-reviewed publications. He has authored and co-authored more than 50 papers and book chapters on hearing disorders and has presented more than 100 papers at medical conferences.
Ali Andalibi, Ph.D., is director of New Technology and Project Development and section chief for Gene Based Therapy in HEI’s Cell and Molecular Biology Department. He is principal and co-investigator on research studies including those focused on the pathogenesis of ear diseases. Dr. Andalibi oversees multiple cell and molecular biology projects including, among others, the role of innate immunity in otitis media. He has co-authored numerous articles for publications. A native of California, Dr. Andalibi attended the University of California at Los Angeles to earn his doctorate in Microbiology and Molecular Genetics. |
