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Vaccine research shows resurgence

Contributions, recent viruses spark interest

By Stephen Smith, Globe Staff, 9/29/2002

AN DIEGO - For a generation of Americans who came of age in the years after World War II, vaccines emerged as the medical Manhattan Project, an all-out assault on the scourges of that era.

Victory was achieved against polio, smallpox, and measles. So swift and sure was triumph that the nation's vaccine-making infrastructure was largely mothballed.

Now, after languishing for decades, vaccine research has dramatically accelerated. Driven by the twin specter of bioterrorism and newly emergent infections such as West Nile virus, research energy and money is pouring into new vaccines to stop anthrax, smallpox, plague, tularemia, and botulism.

This weekend at the premier scientific summit devoted to infectious diseases, the Interscience Conference on Antimicrobial Agents and Chemotherapy, researchers reported progress in developing an inoculation against Legionnaires' disease, described the safety and effectiveness of a nasal flu vaccine, and showed how vaccinations are slowing the spread of deadly childhood meningitis.

Among the issues being discussed were the growing number of illnesses that can no longer be treated effectively with antibiotics and the health care system's response to the threat of bioterrorism.

An elite panel of physicians yesterday encouraged flu shots for all children between the ages of 6 months and 23 months. It was the first time that the Advisory Committee on Immunization Practices, which advises government agencies, had recommended universal flu vaccine for any age group of children.

It showed just how far the infectious disease battlefield has shifted in a generation.

''Thirty years ago, the scientific community was ready to close the books on infectious diseases,'' said Ronald M. Atlas of the University of Louisville, who is president of the American Society for Microbiology, which organizes the conference. ''Infectious diseases were going to be a thing of the past.''

Instead, money is flowing into vaccine research, now in unprecedented amounts, from government agencies as well as private companies and even individual philanthropists such as Bill Gates.

Some of the most important vaccine research is unfolding in the Boston area, at biotech laboratories such as Acambis.

The Cambridge company is in the midst of human trials of a smallpox vaccine, having won a contract from the US Centers for Disease Control and Prevention to produce 209 million doses. And a $3 million award to Acambis from the National Institutes of Health is fueling investigation of a vaccine against West Nile virus, the mosquito-borne illness that has swept from the East Coast of the nation to the West Coast in three years, killing 116 people this year alone.

The scientist in charge of West Nile vaccine development at Acambis released details Friday of his team's latest research, showing that a dozen monkeys given the vaccine were able to thwart the virus even when it was injected into their brains.

The inoculation, known as the ChimeriVax-West Nile vaccine, is built on the molecular backbone of an existing vaccine for yellow fever, which belongs to the same family of viruses as West Nile. By swapping out key yellow fever genes and replacing them with genetic material from the West Nile virus, scientists created a vaccine that they believe will have the same level of safety and effectiveness as the widely used yellow fever vaccine.

Humans could begin getting experimental doses of the West Nile vaccine within six months.

''The interest in the vaccine has increased a lot this year,'' said Juan Arroyo, leader of the ChimeriVax project at Acambis. ''There is talk about how fast we can go through the clinical trials.''

But as that process begins - it is expected to take three to five years before the vaccine is on the market - vital questions remain. They are the same questions that bedevil much of the vaccine research newly underway.

Who should get these vaccines, only the most vulnerable or everyone? How much will they cost? When should they be used?

''If you were to have a vaccine that prevents against skin cancer,'' Arroyo said, posing a hypothetical scenario, ''would you give it to everyone or only to people who spend a lot of time in the sun? Those are the questions we have to answer.''

Back in the days when Dr. Arthur M. Friedlander labored in relative obscurity at the US Army Medical Research Institute of Infectious Diseases, the question of who might get vaccinated against anthrax was straightforward: military troops.

That changed with the arrival nearly a year ago of the first anthrax-laden letters to media outlets and government offices.

''These events have really irrevocably altered our lives and the practice of medicine and public health,'' said Friedlander, the Army's top specialist on anthrax.

But the quest for a successful vaccine can be elusive. More than two decades into the AIDS epidemic, scientists still seek not just the right bullet but also the right target to stop a virus renowned and feared for its adaptability. That kind of basic research doesn't come cheap, and big pharmaceutical companies prefer to spend their money developing drugs that can treat patients whose chronic conditions require a lifetime of medication.

At the San Diego meeting of infectious disease specialists, the scientist who is marshaling an international campaign to develop AIDS vaccines described years of disappointment now being leavened by hope as some experimental vaccines reach the later stages of development.

''The economic incentive for large-scale vaccine research is minuscule compared with drug development,'' said Dr. Lawrence Corey, a University of Washington infectious disease specialist. ''And constructing an HIV vaccine is not a simple engineering project.''

But the pace of AIDS vaccine research has quickened of late, with money from Gates, the Microsoft mogul, helping to convince other contributors that it's a safe bet for research dollars, Corey said.

That money is being spent on an array of novel approaches, including vaccines that would not even attempt to prevent infection. Instead, they would modify replication of the virus in someone who gets infected, with researchers hoping that would result in a virus so weakened that it could not be easily transmitted.

Issuing a call that resonated with the hundreds of scientists who filled a convention center auditorium to listen to him, Corey urged vaccine researchers to press ahead with renewed fervor and to begin major trials of AIDS vaccines, doing for that virus what had been done in an earlier generation to stymie smallpox and polio.

''We have too much opinion and too little data,'' Corey said. ''I would like to know whether the cup is half-full or half-empty. Large-scale clinical trials are needed to know whether we even have any water in the beaker.''

Stephen Smith can be reached at stsmith@globe.com.

This story ran on page A14 of the Boston Globe on 9/29/2002.
© Copyright 2002 Globe Newspaper Company.

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