Specto Design is a Los Angeles
October 20, 2011 - PRESIDENT'S COUNCIL SCIENTIFIC SEMINAR
"Revolutionizing Vaccine Discovery"
Members of the La Jolla Institute's President's Council recently heard from scientist Shane Crotty, Ph.D., whose breakthrough discovery in 2009 is advancing worldwide efforts to improve the speed and effectiveness of vaccine design. Dr. Crotty was chosen as one of America's "Most Promising Biomedical Researchers" by the Pew Charitable Trusts in 2005 and has been a guest on National Public Radio's Science Friday due to his important vaccine work. He is also the discoverer of a potential treatment for smallpox and is working with federal health officials on the possibility of stockpiling the treatment nationally as a safeguard against bioterrorism.
"Vaccines are the most effective medical intervention ever invented aside from clean water," said Shane Crotty, Ph.D., a La Jolla Institute scientist and prominent virology researcher. However, most people would be surprised to hear that only 26 vaccines currently exist worldwide.
"There are a number of scientific challenges that make vaccine development a slow, difficult process," said Dr. Crotty. "Consequently, we have many dangerous diseases, such as HIV, malaria and dengue virus, where no vaccines exist, and millions of people die every single year as a result."
Dr. Crotty believes one of the main obstacles to creating new vaccines is current design methods. "Vaccine development is primarily an empirical process, not a structured process," he said. "It involves trial and error and observation, rather than being based on in-depth knowledge of cellular mechanisms."
Dr. Crotty is working to change that model. "I'm focused on understanding how to design vaccines in a more rational way," he said. "We need to adopt an engineering approach that uses a step-by-step clearly understood process aligned with how the body fights infection." Dr. Crotty is leading the way through his groundbreaking discoveries on the mechanisms of immune memory. Immune memory refers to the immune system's ability to remember and protect us against viruses, bacteria or other invading pathogens and is the basis for successful vaccines.
"A previous encounter with a virus "teaches" the immune system to recognize and remember that exact pathogen," he explained. "A vaccine's purpose is to do the same thing without the person being infected." To accomplish this, vaccines contain pieces of pathogens that cement themselves in the immune system's memory, without making the receiver sick. Upon reencountering the actual virus after vaccination, the immune system triggers antibodies, which are like cellular ninjas that seek out and destroy the previously encountered pathogens.
"Twenty-four of the 26 existing vaccines work by triggering antibodies," said Dr. Crotty. "My lab focuses on how to make better antibody responses."
It was while studying this process in 2009 that Dr. Crotty discovered the gene, BCL6, that switches on the production of antibodies- an enormous finding in terms of its long-term benefit to science and society as a whole. Published in the journal Science, the landmark finding opens the door to developing ways to boost antibody production, thereby creating stronger and more effective vaccines.
In addition to identifying the specific gene, Dr. Crotty also clarified the key players in the molecular cascade triggered by the BCL6 gene. Critical in that process is the T follicular helper (Tfh) cell, he found.
"We've shown that Tfh cells are essential to the production of antibodies," he said. The next step is figuring out the best way to activate these cells. "Currently, we are vigorously determining the most important signals to drive Tfh cell development," he said. "This will be vital to getting a good antibody response and a good vaccine."
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