July 18, 2013

VU researchers ‘goldsmith’ new RSV vaccine approach

Vanderbilt vaccine researchers are using gold nanotechnology to develop a new approach to making vaccines.

Vanderbilt vaccine researchers are using gold nanotechnology to develop a new approach to making vaccines.

James Crowe Jr., M.D., director of the Vanderbilt Vaccine Center, is lead author of a study published June 26 in the journal Nanotechnology that shows tiny particles of gold can be shaped and coated to mimic the microbe respiratory syncytial virus (RSV), a major cause of childhood disease.

James Crowe Jr., M.D.

“Putting a protein on particles is not new, but using gold in this way to mimic the size and shape of a virus is. We can control the shape and we think this is a novel approach and should work better than conventional protein vaccines,” said Crowe, also Ann Scott Carell Chair and professor of Pediatrics and Pathology, Microbiology and Immunology.

Nanoparticles are used to deliver many medical treatments in humans, but this is the first time gold has been used on the nano scale to mimic a virus and produce an immune response.

Crowe said gold was selected because it has been used for decades, for example as an injection to treat some patients with arthritis.

“We figured out a way to make the protein from the surface of the virus in the lab, and were able to coat the gold nanoparticles with it. The particle ends up being about the same size and shape as RSV, so we think it mimics the real virus particle and is able to deliver the protein to trigger the immune response,” Crowe said.

A critical RSV protein called the “F protein,” or fusion protein, is generally what triggers the natural human immune response to an RSV infection.

In the lab, Crowe and his colleagues produced the F protein and successfully coated the gold nanoparticles with it. Then researchers exposed two key cells from the human immune system to the particles. The first were “antigen presenting” cells, called dendritic cells. These cells recognized the particles as a virus, and picked them up. They then successfully presented the particles to one of the main virus response cells in the immune system, called T-cells, and the T-cells responded by replicating.

Researchers have been trying for many years to find a way to deliver the F protein to immune cells in such a way that they will recognize and safely mount a protective response. Until now, there has been little success.

“Using a weakened live virus has been a central thrust for many vaccines, but this virus infects very young children, and it’s hard to create a live virus that both works to immunize but does not grow to such levels that it causes illness,” Crowe said. “The goal in protein vaccine development has been to create something non-living that doesn’t have potential to grow out of hand and make children sick.”