GALVESTON, Texas—The University of Texas Medical Branch at Galveston has received a $9.5 million grant from the Bill & Melinda Gates Foundation to better control influenza epidemics in the developing world.

The three-year grant will allow UTMB scientists to help accelerate development of a new kind of flu vaccine that aims to strengthen people’s natural immunity by linking the two main mechanisms of immune defense, innate and adaptive immunity. Traditional medical opinion has held that the innate and the adaptive immune systems operate independently. However, the candidate vaccine activates both mechanisms in sequence, similar to what happens during an infection, generating robust antibody and cell-mediated responses.

“We deeply appreciate this generous support from the Gates Foundation, which permits us to test a very promising proposed vaccine and vaccine technology,” said the principal investigator for the grant, professor Lawrence R. Stanberry, chairman of the UTMB Department of Pediatrics and director of the Sealy Center for Vaccine Development.

“We think this approach has the potential to provide more effective, better-targeted and cheaper influenza vaccines throughout the world, allowing developing countries and regions access to an influenza vaccine which currently does not exist,” Stanberry added.

The proposed vaccine targets a conserved antigen on the surface of the influenza virus, Stanberry said. This is an antigen that remains the same from one year’s flu virus to the next.

Under the contract with the Gates Foundation, UTMB’s Slobodan Paessler plans to test the candidate vaccine in mice in UTMB’s Robert E. Shope, M.D., Laboratory, a Biosafety Level 4 (maximum containment) facility. Assuming those tests are successful, Dr. Christine Turley, vice chair for clinical services in the Department of Pediatrics and associate director of clinical trials and clinical research in the Sealy Center for Vaccine Development, is scheduled to oversee Phase I clinical trials in healthy adults to determine safety of the vaccine.

VaxInnate Corporation, a privately held biotechnology company based in New Haven, Conn., that developed the proposed vaccine, reports that it fully protected mice from flu in company-sponsored tests. Under a contract negotiated on behalf of UTMB by senior technology manager Peter J. Kelleher and Andrew G. McNees, associate director for administration of the Sealy Center for Vaccine Development, VaxInnate will perform a significant amount of additional work as a UTMB-selected subcontractor on the grant.

Current influenza vaccines are made using a cumbersome approach and technology developed more than half a century ago. First, epidemiologists must predict which strains of the flu will be circulating the following fall and winter. Then scientists formulate a vaccine targeting the likeliest ones.

Flu viruses typically are grown in live, fertilized chicken eggs, and then laboriously harvested, purified and processed to recover viral antigens. Using these egg-based systems, it takes six to nine months to manufacture and release a year’s batch of vaccine—meaning that the process begins long before it is clear how much demand there will be for a specific vaccine. This makes it hard for physicians and drug companies to respond quickly to public health emergencies.

Stanberry said scientists at VaxInnate have determined that the company’s proposed vaccine can be produced much faster than current flu vaccines grown in chicken eggs or cell cultures, narrowing the interval to just a few months and thus allowing a much more rapid response to emerging flu strains. This is possible because the projected vaccine can be manufactured in bacteria using recombinant DNA techniques.

VaxInnate has reported that its novel approach is based on the ability of what are known as “toll-like receptors” on disease-fighting white blood cells to recognize certain molecular patterns that trigger innate immune responses.

The company’s proprietary technology calls for fusing influenza antigens with bacterial flagellin, a component of the long, hair-like tails that propel bacteria, which is one of the molecular patterns recognized by cellular TLRs. The specific method involves inserting into bacteria a circular DNA “vector” coding for the fused flagellin-antigen product. The DNA then directs the bacteria to synthesize the combined product. VaxInnate has said its prior research indicates that fusing flagellin to antigens leads to a stronger vaccine than would injecting a mixture of the two unattached components.
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