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Vaccines that attack

Boston-area firms working to develop vaccines against herpes, diabetes, other diseases

centers for disease control and prevention

More than 500 million people worldwide have genital herpes, a lifelong, incurable infection that can lead to ugly, painful flare-ups. Cancer therapy or other immune problems can spark a recurrence, and the virus makes people more vulnerable to HIV infection.

Attempts to develop a vaccine to prevent the spread of herpes have failed, but three local efforts to develop therapeutic vaccines may eventually provide a solution for those with herpes, as well as a wide range of other illnesses.

SUZANNE KREITER/GLOBE STAFF

Researcher Shane Larson at Genocea Biosciences in Cambridge, one of several firms working on vaccines against herpes and other diseases.

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Just as conventional preventative vaccines use the immune system to prevent disease, therapeutic vaccines use the immune system to target and kill a disease already in progress.

The idea is not a new one. Dr. Carl June, a professor at the University of Pennsylvania School of Medicine, said he has been working to develop therapeutic vaccines for 30 years.

But now, after major failures and minor victories, researchers may at last have a deep enough understanding of the immune system to make a difference, June and others said. And the Boston area is a major hub of this research.

“Right now, we’re finally at a point where at least the preliminary tools exist for us to deliver something that will start a new trend in medicine,’’ said Garo H. Armen, chief executive of Agenus Inc., a Lexington biotechnology company that is developing a therapeutic herpes vaccine.

In addition to those that attack herpes, therapeutic vaccines are currently under development for hepatitis C, chlamydia, HIV, diabetes, other autoimmune disorders, and even - at Selecta Biosciences in Watertown - a vaccine against nicotine.

‘THE GENETICS AND GENOMICS REVOLUTION OF THE ’90s IS JUST NOW HITTING VACCINES. . . . WE’RE CATCHING UP TO THE REST OF THE FIELD OF DRUG DISCOVERY.’

CHIP CLARK GENOCEA BIOSCIENCES
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(A Globe story in December addressed similar efforts to treat cancer, which is the most advanced area of therapeutic vaccine research, with dozens of treatments under development.)

For years, vaccine research was considered a sleepy backwater in the drug development world, said Chip Clark, chief executive of Genocea Biosciences, which is developing its own therapeutic vaccine against herpes.

Then, conventional vaccines to prevent pneumonia and human papilloma virus began earning big returns. A six-year-old therapeutic shingles vaccine, Zostavax, proved that vaccines can treat an existing infection. And the success of the therapeutic prostate cancer vaccine Provenge, which came on the market in 2010, has awakened interest at major pharmaceutical companies and biotech start-ups.

“The genetics and genomics revolution of the ’90s is just now hitting vaccines,’’ Clark said. “We’re catching up to the rest of the field of drug discovery.’’

For a therapeutic vaccine to work, it has to have the right target, the right ammunition, and enough power to get that ammunition to its quarry, Armen said - all without triggering dangerous side effects.

SUZANNE KREITER/GLOBE STAFF

At Genocea Biosciences in Cambridge, researchers like Danielle K. Garvie are working on a vaccine against herpes. The company will be testing its product this year and hopes to apply the same theory to develop vaccines against other diseases.

Agenus holds a patent on an adjuvant, which adds ammunition to the vaccination. The QS-21 STIMULON adjuvant was recently shown to be safe and effective in a malaria vaccine given to 6,000 African children.

Agenus’s therapeutic vaccine uses this adjuvant and targets 32 gene sequences unique to the virus; most other drugs attack just one or two sequences, allowing many viral strains to escape. Later this year, the company will begin testing its vaccine in 70 patients, with results expected about a year later.

So far, Armen said, scientists “have gone after singular approaches, linear paths to trying to attack this bug and the disease, and those have not worked. Our approach is putting it all together for the first time.’’

A few miles away in Kendall Square, scientists at Genocea are using a different weapon to take aim at herpes. Previous attempts to create a vaccine for diseases like herpes have all failed, Clark said, because they have used the wrong arm of the immune system. Most classic vaccines stimulate the B-cell arm, he said, which makes antibodies that can target incoming viruses and remember them later. But Genocea is instead attacking them via the T-cell arm, which launches armies to hunt down invaders.

The company scans the blood of people with a disease like herpes and identifies those whose T-cells naturally keep the disease in check. Then, Genocea identifies the proteins behind this protection.

The company hopes that giving the proteins to patients with a weaker natural reaction will trigger their immune system to step up and fend off the virus - a theory Genocea will be testing in people with herpes later this year.

The same theory should work with a vast array of other diseases, said Clark, whose company’s science is girded by the research of Darren Higgins, a professor of microbiology and molecular genetics at Harvard Medical School.

In a third approach against herpes, vaccine maker Sanofi Pasteur is working on a vaccine based on research by David M. Knipe, chairman of the Harvard PhD program in virology. Knipe developed a prophylactic vaccine, using live, mutant viruses to trigger an immune response. Testing in people will begin later this year, but he also hopes the same vaccine will also be able to treat people already infected with the virus.

“Work in my lab is continuing to try to improve the vaccine while the first generation is being produced to get it into people,’’ he said.

Selecta Biosciences, based in Watertown, is taking an entirely different tactic, using nanotechnology developed by Robert S. Langer of the Massachusetts Institute of Technology to force the immune system to recognize nicotine - which is normally too small to be detected. Triggering an immune response to nicotine will block it from reaching the brain, and smokers will not get the high that makes the habit pleasurable, said Lloyd Johnston, Selecta’s senior vice president of research and development.

That should make quitting easier and provide longer-term relief than a patch or pill, he said. With the first trials in people slated to be completed in the first half of this year, it is too soon to tell how long the effect will last or whether their approach will work at all.

There is still a lot researchers don’t know about how to amp up the immune system to fight disease. A late-stage clinical trial for Type 1 diabetes recently failed, according to results published this month in the New England Journal of Medicine. Researchers speculated that a flu vaccine that some trial participants received around the same time may have weakened their response.

Knipe said the field of therapeutic vaccines is littered with such failures, “but the success of the shingles vaccine . . . shows that therapeutic vaccines are feasible and raises our hopes for more successes.’’

Karen Weintraub can be reached at karen@karenweintraub.com.
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