June 15, 2007

Genetics key to vaccine advances

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Kathryn Edwards, M.D., chats with Brent Polk, M.D., at last week’s Discovery Lecture. (photo by Susan Urmy)

Genetics key to vaccine advances

New genetic approaches need to be applied to complex vaccine challenges, Kathryn Edwards, M.D., a leading vaccine researcher at Vanderbilt University Medical Center, said last week.

If they are, “the progress in the next century will be even greater than the last,” she said.

“How wonderful would it be to be able to free the world of malaria, TB and HIV? The potential is there. We just need to do it.”

Edwards, a professor of Pediatrics who directs the Division of Pediatric Clinical Research, has reason to be optimistic.

During her Vanderbilt Discovery Lecture on June 7, she gave several examples of new vaccine technologies that are showing promise.

Among them is “reverse vaccinology.” Instead of injecting a virus or bacteria into mice and developing vaccines from the antibodies that are produced against it, scientists start from the opposite direction — they analyze the pathogen's genome to identify possible vaccine candidates.

Researchers at The Institute for Genomic Research in Rockville, Md., for example, have analyzed multiple genomes of group B Streptococcus, a bacterium that can cause life-threatening infections in newborns, to uncover antigens, or protein markers on the bacterial cell surface, which could be used to make an effective vaccine.

Another approach is the insertion of DNA from the pathogen into an adenovirus that has been modified so that it cannot cause illness. (Adenoviruses can cause upper respiratory tract infections). The adenovirus thus serves as a “Trojan horse” to present the DNA to the immune system, and stimulate immunity against it.

Edwards and her Vanderbilt colleagues currently are testing an adenovirus vaccine to prevent malaria, which kills more than 1 million people every year.

One of the major challenges facing vaccine development is dealing with the issue of safety. As the incidence of vaccine-preventable diseases declines, more attention is paid to the relatively rare instances of adverse vaccine-related events, Edwards said.

“We're victims of our success,” she said. “If you don't know about the disease polio, then you don't know it's important to be vaccinated to prevent it.”

Here again, research and technology can help.

Last year Edwards and colleagues at Vanderbilt, Dartmouth Medical School and the National Center for Genome Resources in Santa Fe, N.M., reported that protein messengers involved in inflammation were responsible for temporary and minor side effects, including fever, swollen lymph nodes and rash, which can follow smallpox vaccination.

In the future, doctors may be able to identify patients who are genetically susceptible to side effects, and prescribe vaccines that are least likely to elicit them, she said.

To maintain public support for vaccines, it also is important to be careful about how they are marketed, Edwards added.

Controversy erupted when manufacturers of a newly licensed HPV vaccine, which can prevent cervical cancer caused by four strains of the sexually-transmitted human papilloma virus, sought to make the vaccine mandatory for young girls.

“It's a great vaccine,” Edwards said. “The problem is that (for the manufacturer) to work through the government … to mandate this vaccine is a bit of a conflict of interest.”

While many young men and women are infected by HPV, vaccination should be voluntary, she added.