Posted on September 10th, 2012 by msequeira
David Peabody, PhD, University of New Mexico Professor of Molecular Genetics and Microbiology, and Bryce Chackerian, PhD, UNM Associate Professor of Molecular Genetics and Microbiology, think they’ve found a better way to build a vaccine—one which might eventually lead to a vaccine for cancer.
Many of today’s traditional vaccines start with the disease-causing virus itself and then either weaken or kill it. Newer vaccines use virus-like nanoparticles (VLPs). A VLP is just the capsid, or protein shell, of a virus, so it can’t cause disease and is cheaper and faster to produce. But because the VLPs in the vaccine look like virus particles on the outside, the immune system responds as if it were combatting a real virus.
“VLPs are very good at provoking an immune response,” says Dr. Chackerian. When the immune system responds to a virus, it creates millions of antibodies that bind to various regions on the surface of that virus. These binding regions are called epitopes. Dr. Peabody and Dr. Chackerian are using VLPs to engineer highly effective vaccines by mimicking epitopes on the surface of a VLP. They use a VLP that they engineered from a protein of a bacteriophage, or bacteria virus. Because this bacteriophage infects only E. coli bacteria, there’s no danger of human infection. The VLP looks like a tiny soccer ball with peptide sequences—proteins—sticking out from its surface. “The immune system has figured out that these very repetitive structures are a common characteristic of harmful pathogens, so it responds strongly,” explains Dr. Chackerian. Dr. Peabody and Dr. Chackerian can make those surface proteins look like almost any epitope, so the VLP can be made to look like any virus—or cell.
But as Dr. Peabody asks, “What if you don’t know what the target protein should be? For example, suppose you have an antibody that you know prevents influenza but you don’t necessarily know what it recognizes, or maybe what it recognizes is very complex.” Dr. Peabody and Dr. Chackerian have found a solution for this dilemma.
The process they’ve developed is akin to making a cast for the VLP surface protein. “We make a huge library of genes each with a different randomly-generated peptide sequence in it. Then we create tens of billions of VLPs with different peptides inserted at the display location,” says Dr. Peabody. He goes on to explain that in the process of making these VLPs, the bacteria—like all cells—use another nucleic acid called messenger ribonucleic acid, mRNA, which the VLP encapsulates. “The instructions for making the peptide are inside the particle,” says Dr. Peabody.
Drs. Peabody and Chackerian then take this large population of VLPs and test it with the antibody. Says Dr. Peabody, “We throw away what doesn’t bind, we save what binds. This is called affinity selection. Whatever sequence that VLP has on its surface is well-adapted to binding to the antibody and, presumably, will be able to elicit antibodies that have that same recognition specificity.” Using a process called reverse transcription (RT) they can convert the mRNA back into DNA which can then be used to make many, many more VLPs with the same surface protein. By repeating this process of creating VLPs and using affinity selection to refine the surface protein, Dr. Peabody and Dr. Chackerian are able to develop VLPs that bind very tightly to the antibody and that create the strong immune response in which the body produces many copies of that antibody.
“The best part is that this process takes weeks instead of months or years,” says Dr. Chackerian. “It’s a fairly simple process and we can run affinity selections simultaneously with a lot of different antibodies.” They might even be able to automate it. Drs. Peabody and Chackerian are currently developing several new vaccines using this process.
The ease and speed of their process opens additional possibilities. “We think we can also use our system to develop cancer vaccines,” says Dr. Chackerian. Normally, the body doesn’t create an immune response against its own cells—that’s autoimmunity and is usually very harmful. “But in certain cases,” says Dr. Chackerian, “it might be useful to induce an immune response against a self-protein, like when that self-protein is part of pathology.”
Their concept for a cancer vaccine is that instead of starting with an antibody against a virus, they would start with an antibody that’s used as a therapy for cancer. One such antibody, for example, is the antibody against the HER2/neu protein, which is part of the treatment for an aggressive form of breast cancer. Of course, there are many more risks—and more severe risks—with inducing an autoimmune response and Dr. Peabody and Dr. Chackerian are just starting studies in this area. “It’s terribly important to select targets that are just on the cancer cells. The immune system doesn’t recognize cancer cells as being different from regular cells very well,” says Dr. Peabody. Nevertheless, the tantalizing possibility is there.
About the UNM Cancer Center
The UNM Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute (NCI)-designated cancer center in the state. One of just 67 NCI-designated cancer centers nationwide, the UNM Cancer Center is recognized for its scientific excellence, contributions to cancer research and delivery of medical advances to patients and their families. It is home to New Mexico’s largest team of board-certified oncology physicians and research scientists, representing every cancer specialty and hailing from prestigious institutions such as MD Anderson, Johns Hopkins and the Mayo Clinic. The UNM Cancer Center treats more than 65 percent of the adults and virtually all of the children in New Mexico affected by cancer, from every county in the state. In 2010, it provided care to more than 15,800 cancer patients. The Center’s research programs are supported by nearly $60 million annually in federal and private funding. Learn more at http://cancer.unm.edu.
UNM Cancer Center contact information
Dorothy Hornbeck, JKPR, (505) 340-5929, firstname.lastname@example.org
Michele Sequeira, UNM Cancer Center, (505) 925-0486, email@example.com
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