Physicans preparing to deal with the anticipated spread of the novel influenza A(H1N1) virus are awaiting the results of a series of U.S. clinical trials aimed at gathering critical data about two candidate vaccines.

The studies which were initiated under the directorship of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, got underway at the institutes's eight Vaccine and Treatment Evaluation Units (VTEUs).

The goal was to quickly evaluate pilot vaccine lots from two manufacturers, Sanofi Pasteur and CSL Biotherapies, to determine vaccine safety and efficacy in inducing protective immune responses.

"It's an exciting event," Dr. Robert B. Belshe, an internist who directs the VTEU at St. Louis University School of Medicine, said of the trials. "We don't have a major antigenic change very often for flu. This year we are clearly in the midst of the early pandemic. But this pandemic is going to be much different than other pandemics."

In contrast to their counterparts during previous pandemics, today's clinicians have good diagnostics at their disposal.

"We know how to make vaccines, and we know how to treat influenza with antivirals. The race is on right now to make as much vaccine as possible and get it into the highest risk population, which for this particular virus is children," he said.

According to a written statement issued by the NIH, initial studies at the VTEUs were designed to examine whether one or two 15-mcg doses of H1N1 vaccine would be needed to induce a potentially protective immune response in healthy adults (aged 1864 years old) and elderly people (aged 65 and older). They studies also were aiming to assess whether one or two 30-mcg doses would be needed. Doses would be given 21 days apart. If early data indicate that the vaccines are safe, similar trials in healthy children (aged 6 months to 17 years) will begin.

Another set of trials was planned to examine the safety and immune response in healthy adult and elderly volunteers given the seasonal flu vaccine plus a 15-mcg dose of novel H1N1 vaccine. The H1N1 vaccine would be given to different sets of volunteers either before, after, or at the same time as the seasonal flu vaccine. If early data indicate that these combinations are safe, similar trials in healthy children will start.

"I would anticipate that the monovalent H1N1 vaccine will behave exactly like the seasonal flu vaccine in terms of safety and adverse events, meaning it will probably cause some local pain, but nothing else," said Dr. Belshe, professor of infectious diseases and immunology at St. Louis University.

"The biggest challenge is, how do we get vaccine to as many high-risk people as possible? What's going to happen next year? Is this new virus going to replace the previous circulating H1 virus? I wouldn't be surprised if it did. If so, we will change the seasonal vaccine next year to include the new H1 and drop the old H1."

In previous years, Dr. Belshe has enrolled in vaccine clinical trials as a volunteer, but said he won't be doing so this time around. "We discourage investigators from vaccinating themselves. There is a time-honored tradition of physicians experimenting on themselves, but under the current system of institutional review boards and regulatory standards, that would be frowned upon," he said.

Dr. Belshe was quick to note, however, that he will take the vaccine as soon as it's available for general use. "I am certainly not afraid of the vaccine," he said. Health care workers are a high-priority group to receive immunization against the novel H1N1 virus, according to recommendations issued recently by the Centers for Disease Control and Prevention.

In the meantime, he said, being part of the national discussion on how to respond to the current pandemic "is very exciting, and to be able to provide advice and experience from our many years of clinical trials on how to successfully design a trial and answer the critical questions [has] been very rewarding."

The other VTEUs are Baylor College of Medicine, Houston; Children's Hospital Medical Center, Cincinnati; Emory University, Atlanta; Group Health Cooperative, Seattle; University of Iowa, Iowa City; University of Maryland School of Medicine, Baltimore; and Vanderbilt University, Nashville, Tenn.

Dr. Belshe has been a consultant to several manufacturers of vaccines, including MedImmune, Sanofi Pasteur, GlaxoSmithKline, and Novartis.

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'The race is on right now to make as much vaccine as possible and get it into the highest risk population.'

Source DR. BELSHE

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The newly identified H1N1 virus (above) could replace the previous H1 virus.

Source ©CDC

Candidate H1N1 Vaccines Enter Clinical Trials