DNA vaccines explored as immunotherapy
DNA vaccines explored as immunotherapy
Until recently, DNA-based vaccines weren’t looking promising. Lab rats vaccinated with DNA and then infected with TB seemed to fare about as well as mice getting BCG vaccination, which is to say, not so well. Recently, however, scientists have begun looking at DNA vaccines with new respect for possible use as immunotherapy instead of preventive therapy.
British scientist Douglas Lowery caused a stir when he published results of work in which he infected mice with TB, treated them with TB drugs, and then gave them a DNA vaccine. When he gave the mice steroids to see if their TB infection would rebound, he found they appeared to be protected against reactivation.
"It was beautiful work, and a very clever strategy," says William Bishai, MD, PhD, assistant professor at the Johns Hopkins University Center for TB Research in Baltimore. "I’m actually more upbeat about DNA vaccine as immunotherapy than as preventive therapy. That’s because heat-killed vaccines aren’t immunogenic; that is, even if you take the whole bug and heat-kill it, with all its DNA and all its antigens, it doesn’t work. So it doesn’t seem reasonable that it would work if you reduce it to just some DNA. But trying it as immune therapy — that seems very futuristic."
Lowery’s work also suggests a DNA vaccine may shorten therapy, says Robert Seder, MD, chief of the clinical section in the laboratory of clinical investigation at the National Institutes of Health. Seder is tinkering with DNA vaccines in much the same way. Lowery’s work "allows the possibility that maybe we could shorten treatment by bolstering the immune system against reactivation and maybe even against reinfection," he says. The standard length of treatment wasn’t abbreviated in the work Lowery did, he adds, because the chemotherapy portion plus the immunotherapy part add up to about six months of treatment. What’s more, Lowery infected his mice intravenously, not via the pulmonary route; that shortcoming has Seder itching to learn what will happen if the experiment is repeated with a pulmonary model.
"Whether you can pull it off practically — make it work in humans — is another issue," he says. "But it makes good scientific sense, and it helps lay the foundation for using DNA not as a prophylactic but as an immune therapy."
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