Scientists at the University of Buffalo report the development of a novel hybrid system that was designed to deliver vaccines that contain genetically engineered DNA to fight HIV, cancer, influenza, and other disorders.

The team described its research (“Hybrid biosynthetic gene therapy vector development and dual engineering capacity”) in the Proceedings of the National Academy of Sciences. “The technology that we're developing could help take immunization to the next level,” said Blaine A. Pfeifer, Ph.D., an associate professor in the department of chemical and biological engineering in the school of engineering and applied sciences. “By improving the delivery of DNA vaccines, we can potentially harness the human immune system in new ways to fight everything from the flu and herpes to HIV and cancer.”

To create DNA vaccines, scientists analyze disease-causing sources, such as a pathogenic microbe. They then isolate copies of the microbe's genes (usually one or two) responsible for the disease. The genetically engineered DNA is injected into the body and directs the production and presentation of antigens, which provoke an adaptive immune response capable of destroying the disease.

Essentially, the body's own cells become vaccine-making factories that create the antigens necessary to stimulate the immune system, according to the National Institute of Allergy and Infectious Diseases.

In theory, DNA vaccines can generate broad immune responses; they are relatively inexpensive to create; and they can't cause the disease because they don't contain the source of the disease, only a few of its genes. Dozens of clinical trials involving DNA vaccines are under way. Most are investigating treatments for HIV and cancer, while others involve influenza, hepatitis B and C, HPV, and malaria.

A problem limiting the effectiveness of some DNA vaccines, however, is that they do not sufficiently stimulate the immune system. Scientists say this is due, in part, to the inefficient delivery of the genes. For example, some travel to the wrong place while others get caught in intracellular traffic jams.

To address the problem, Dr. Pfeifer and his students collaborated with Anders Hakansson, Ph.D., formerly of the UB school of medicine and a senior co-author of the study.

The team combined a bacterial cell and a synthetic polymer to create a hybrid. Designed to target specific antigen-presenting immune cells and more efficiently deliver genes to the nucleus of those cells, the hybrid outperformed the two individual delivery vehicles when tested in a mouse model.

“[Our] approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents,” wrote the investigators. “Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy.”

“The hybrid provided a synergistic boost in delivery effectiveness due to its dual nature,” said Charles H. Jones, a doctoral candidate in the department of chemical and biological engineering at UB and the study's first author. “We also determined that it's relatively inexpensive to create and flexible in terms of use. The results thus far are encouraging.”

Dr. Pfeifer said the team continues to test the vehicle in different models with the goal being to create a vehicle that will be useful for many DNA vaccines. 








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