August 4, 2011

Study aims to speed vaccine creation

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Leigh Howard, M.D., left, Andrew Link, Ph.D., and colleagues are using novel approaches to examine the early immune reaction to new vaccines. (photo by Joe Howell)

Study aims to speed vaccine creation

Vanderbilt’s Vaccine and Treatment Evaluation Unit has received a $1.6 million contract from the National Institutes of Health for a novel approach to vaccine development.

Andrew Link, Ph.D., associate professor of Pathology, Microbiology and Immunology, and Kathryn Edwards, M.D., director of the Vanderbilt Vaccine Research Program, are the principal investigators for an 18-month project to use a “systems approach” to examine the early immune reaction to vaccination.

Kathryn Edwards, M.D.

Kathryn Edwards, M.D.

“A systems biology approach is extremely appealing because it may allow us to know much sooner if a vaccine is safe and effective,” Edwards said.

“After studying vaccines for more than 30 years and generally injecting and waiting to measure immunity one month later, we may ultimately be able to detect a successful immune response within one to three days. This is truly amazing.”

The systems approach, also called systems biology, is an emerging science that integrates disciplines like immunology, functional genomics and bioinformatics. It will be used to describe complex interactions that occur within the immune system as a vaccine works its magic.

“We believe the key is to look at what happens in the immune system at earlier time points. We want to know, in that initial response, how does the vaccine teach or train the next response,” Link said.

A systems approach takes a holistic snapshot of cellular and chemical reactions in cells. When these snapshots are taken at several points within the first days of a vaccine’s injection, a “meta-view” of the innate, or early, immune response can be compiled, integrated and analyzed to predict how the vaccine works.

The first vaccine the VTEU will examine with the systems approach is the H5N1, or avian flu, vaccine. Pediatric Infectious Diseases fellow Leigh Howard, M.D., who will be conducting the clinical portion of the trial, says global health experts are warily eying the near 60 percent mortality rates for the (so far) isolated cases of avian flu.

There is concern traditional vaccine development may take too long. Tests of vaccines thus far have been disappointing, requiring more than six times the traditional flu vaccine dose for the H5N1 avian flu vaccine to work.

“Since current H5N1 vaccines aren’t very effective, what we learn in this systems approach can speed our progress toward preventing the potential of H5N1 pandemic disease, and it will be relevant for understanding vaccine responses to other strains of influenza as well,” Howard said.

Vanderbilt’s VTEU will examine an adjuvant called AS03, developed by GlaxoSmithKline. Adjuvants are additives, like oils or aluminum salts, which amplify a person’s response to vaccines. The VTEU will recruit 20 people, half of whom will receive the H5N1 vaccine with the AS03 adjuvant while the other half will receive the vaccine alone.

Participants must be 18 to 49 years old and healthy. Blood and urine samples will be collected at three time points before vaccination, then at days 1, 3, 7, 28 and 56 after vaccination. The NIH funding will allow Vanderbilt to achieve coordination of multiple tests of the samples within hours, allowing researchers to capture a dynamic process as it unfolds.