Vaccine defense and defense vaccines
Mayo Clinic researchers are seeking safer vaccines against pandemics and better protections against possible biological terrorist attacks. The two have similarities: They can be potentially stopped through scientific discoveries and human cooperation. Mayo's Vaccine Research Group is a leading force in this effort.
Gregory Poland, M.D.
Mayo Clinic vaccinologist Gregory Poland, M.D., came home one evening and was met by his then 6-year-old son.
"Daddy, I wish you worked at a chocolate factory."
"And why is that?"
"Because right now you work at a shot factory, and we have to get shots. If you worked at a chocolate factory, we would get candy."
While Dr. Poland tells this story often, he quickly adds that in America the average 10-year-old will have received 38 doses of vaccines. And that, he says, is a very good thing.
"We've prevented them from getting the diseases that routinely took kids' lives," Dr. Poland says.
The "shot factory" is Mayo Clinic's Vaccine Research Group or VRG, which Dr. Poland founded and continues to guide in its third decade. He is also the Mary Lowell Leary Professor of Medicine and Professor of Medicine, Infectious Diseases, Molecular Pharmacology and Experimental Therapeutics at Mayo. Dr. Poland also directs Mayo's Program in Translational Immunovirology and Biodefense, and is editor-in-chief of the journal Vaccine.
Mayo's VRG is comprised of two dozen people, ranging from M.D. and Ph.D. investigators to technicians and other lab staff, nurses, statisticians and administrative personnel. One of the largest vaccine research groups in the world, it is also prolific, averaging a research article every 10 to 14 days.
The group has three primary missions: Developing and testing novel vaccines; understanding the genetic "drivers" of immune response to viral vaccines; and developing biological defense vaccines.
"Right now, we think of vaccines solely as a biologic that we give to protect against classic infectious diseases, but vaccines are being developed against diabetes, obesity, dental cavities, heart disease, Alzheimer's disease, and cocaine and nicotine dependence," he explains. "Our concept of vaccines will enlarge considerably in this century."
While the Mayo VRG places primary emphasis on thwarting influenza, it is also studying bioterrorism agents — mainly anthrax and smallpox — and has recently concluded the largest clinical trial to date of an anthrax vaccine. This is an extensive collaboration involving the Center for Disease Control (CDC) Walter Reed Army Hospital, and Emory and Baylor universities, as well as Mayo's Clinical Research Unit and the chair of pediatrics, Robert Jacobson, M.D.
The group enrolled 300 volunteers from Rochester and surrounding communities who received multiple injections and blood tests over nine years. The attempt was to determine if a vaccine could be administered intramuscularly rather than subcutaneously and if the number of doses could be altered to maintain a high level of immunity. The safety of the anthrax vaccine was highly controversial, yet the Mayo Clinic group successfully carried out the study, which will conclude at the end of August, retaining 95 percent of the participants. The researchers concluded that one of the doses can be dropped; part of a preliminary study has been published (JAMA, 2008).
Dr. Jacobson is one of Dr. Poland's chief Mayo collaborators. In this anthrax project, he conducted clinical studies, including recruiting participants and overseeing follow-up interventions. Dr. Poland handled the overall administrative and laboratory issues. The two doctors persuaded the CDC to fund a second arm of the study where they are trying to discover the genetic bases of the immune response to the anthrax vaccine.
It was five years ago that Dr. Poland received a multi-million dollar grant from the National Institutes of Health (NIH) to study a smallpox vaccine. He recently received a $6 million five-year extension to continue the work. The support of NIH and the results from the research have positioned the VRG as one of the international leaders of smallpox research and smallpox vaccines. In 2009, the VRG received a patent for smallpox peptides that it discovered and is now using to make a new, safer vaccine. Mayo Clinic is now negotiating with a biotechnology company to see that discovery developed into a new vaccine.
"We are trying to understand the underlying genetic bases of smallpox immunity, and the profiles of smallpox immunity, so that we understand at a very comprehensive and deep level what stimulates and maintains immunity, and even how immunity is defined," he says. The team is testing another smallpox vaccine in animal models.
In this and other work, Dr. Poland worked closely with Robert Bergen, III, Ph.D., head of Mayo's Proteomics Research Center and Kenneth Johnson of the Mass Spectrometry core laboratory.
"We're grateful to have a whole network of collaborators and laboratories at the Mayo Clinic that help us in this work," Dr. Poland says. "I'm completely dependent on two groups here, one in bioinformatics led by Yan Asmann, Ph.D., and the other in statistical genetics group, involving Ann Oberg, Ph.D., and Shane Pankratz, Ph.D."
The 30th anniversary of the eradication of smallpox in nature was celebrated in May; however, strains of the laboratory virus can be stolen or synthesized by terrorists.
"So we can never be without a vaccine against it, a safer vaccine," says Dr. Poland. "Currently, upwards of 30 percent of the population can't get the current vaccine because they have any of a variety of medical conditions that would allow the live vaccine virus to propagate in their body and cause illness or death."
Merging genomics and molecular biology, vaccinomics explores the way immunologists and vaccinologists develop and deploy individualized vaccines. The group's grand theory on vaccinomics, the Immune Response Network Theory, states: Immune responses are the net result of a variety of coordinated, multigenic and epigenetic (the environment surrounding genes) inputs into the immune system. In 2007, this theory was published in Clinical Pharmacology & Therapeutics.
"It's the idea that you might have no risk at all for a disease, and if we knew that, why bother to spend $300 to immunize against it?" Dr. Poland explains. "For instance, it costs about $400 for the human papillomavirus vaccine. There are people who respond after one dose. If we know that, and can improve the genetic drivers of that, we can eliminate the unnecessary cost of giving those people another dose. Another good example is hepatitis B. There are people genetically encoded to never respond to the vaccine. We can use that information to create a better, personalized vaccine."
H1N1 flu virus
Every year a new seasonal influenza vaccine is produced that contains three strains of influenza. One of those strains in the 2010 vaccine will be the California H1N1 virus that caused the pandemic.
"We will almost certainly see H1N1 this fall and winter," he says. "The dilemma is how to convince people of the importance of this. The H1N1 flu took about the same number of lives as the 1968 pandemic. About two million years of life were lost in the United States to this pandemic. It's not trivial."
Dr. Poland is a special government employee with appointments with the U.S. Department of Defense and the CDC. He has sat on every federal committee that deals with vaccines. Representing the American College of Physicians, he and fellow committee members advise the Department of Health and Human Services on vaccines and who should receive them. In his government work, he is particularly proud of one accomplishment.
"I had introduced a resolution to this committee three times to recommend universal influenza immunization, and this past meeting in February they finally approved it," he says proudly. "Now every American will be recommended to receive the influenza vaccine this year."