Engineering Next Generation DNA Vaccines

Dr. David B. Weiner

Dr. David B. Weiner

Doris Ryan works at the Naval Medical Research Center. Her blog post was originally published in Naval Medical Research and Development News.

As part of the U.S. Military Malaria Vaccine Program (USMMVP), the NavalMedical Research Center (NMRC) hosted Dr. David B. Weiner, Professor of Pathology and Laboratory Medicine Chair in the Gene Therapy and Vaccine Program, University of Pennsylvania School of Medicine, to talk about DNA vaccines January 12.

In a project funded by the Malaria Vaccine Initiative at PATH, Weiner is developing a tetravalent DNA vaccine for the prevention of malaria.

Weiner spoke to a packed conference room on his pioneering work developing DNA vaccines. In the early 1990s, Weiner’s group was one of the first to test DNA vaccines in animals and humans, working initially to develop therapeutic vaccines for cancer. More recently, Weiner developed and tested DNA vaccines for HIV and human papilloma virus.

“A collaboration is planned between Weiner’s laboratory, an industry partner, and USMMVP to develop and test DNA vaccines for malaria,” said Navy Capt. Thomas Richie, research coordinator for the USMMVP. “There is hope that the technologies developed in Weiner’s laboratory will help to improve the protection we have achieved with a novel genetic vaccine against malaria here at NMRC.”

The vaccine Richie and his team are working on consists of three priming doses of DNA followed by a boost with an adenovirus vector. Like DNA plasmid rings, the viral vector encodes the malaria proteins and leads to a potent immune response. The NMRC DNA/adenovirus prime/boost vaccine currently protects only about a fourth of those receiving the vaccine, and it is hoped that by using Weiner’s improvements, the efficacy of the vaccine can be increased.

Most recently, Weiner, working in collaboration with a biotech company, has used electroporation to improve the efficiency of DNA uptake into host cells. Electroporation involves injecting the vaccine and then passing a brief electric pulse through the tissue, momentarily permeablizing the cell membranes permitting increased DNA entry. These improvements – optimized plasmid design, cytokine adjuvants, and electroporation – have resulted in huge improvements in the immune response, rekindling excitement in this technology.

DNA vaccines are one form of genetic immunization, in which the DNA encoding a protein, rather than the protein itself, is injected. The DNA enters the vaccine recipient’s cells, which express the malaria protein encoded by the DNA. The fact that the protein is expressed within the host cell, rather than administered exogenously, induces a different, potentially more powerful immune response than traditional protein-based vaccines.

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