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US Navy Tests DNA Vaccine Delivery System 1/8/04
Thu, 2024-01-08 12:22
The Naval Medical Research Center (NMRC), Silver Spring, Md., plans to work with Inovio AS, Oslo, Norway, to conduct trials of Inovio's in vivo electroporation (EP) technology for delivery of DNA vaccines, as part of a Cooperative Research and Development Agreement (CRADA).
The Navy will test the system for effectiveness in delivering its vaccine for Dengue fever, a virus transmitted by mosquito that infected military personnel during World War II and the Vietnam War, and which has caused epidemics in Somalia and Haiti, and other tropical areas.
“DNA vaccines are a very promising technology, but for a better response you need a better delivery [method],” says Curtis Hayes, PhD, director of the infectious disease directorate at NMRC. “Currently, there are no vaccines being used in the field, just personal prevention, like bug spray. We have tested other vaccines that did not produce a strong response. This approach may induce a more vigorous response.”
Electroporation involves the use of brief electrical pulses to temporarily permeabilize cell membranes, which allows various types of molecules, such as DNA and proteins, to enter the cell more efficiently.
The center plans to perform trials on primates challenged with the virus after immunization. Hayes expects the trial to start in about six months. Yet, it may take more than a year until the vaccine can be used because the researchers will need to evaluate the longevity of immune response. If successful, the approach could be adopted by the malaria group at NMRC, he says.
“The Navy has many different vaccine candidates that they want to try to deliver in the muscle,” says Iacob Mathiesen, PhD, CEO of Inovio. “One problem with intramuscular delivery is that the efficiency of gene transfer is quite low. If you inject DNA dissolved in saline, only a few cells will take up the gene and express it. Some people think that this might be the reason why the immunization is quite inefficient and that you don't get the desired effect.”
Inovio's system is specially designed for getting improved transfection of skeletal muscles. “We use very brief electrical pulses in combination with injection,” says Mathiesen. “We apply these pulses at the site of DNA injection, which does something to the membrane that improves the uptake of the DNA and thereby the expression.” The pulses create some slight damage to the muscle tissue, which may also help to facilitate the immune response, he says, but the body repairs the damage over time.
The electrical pulse system has been used for anticancer drug delivery, but is new to skeletal muscle or gene delivery in humans, says Mathiesen. “We do know it works quite well in animals. When compared to injections without pulsing, we see that we improve the efficiency about 100-fold with much less variability. The amount of DNA used can also be reduced significantly.”
“Working with the Navy is important to us because it enables us to generate important primate data,” says Mathiesen. “If it works well, we can expand our collaborations. We hope more organizations will be interested in working with us to deliver their vaccines. There are many different vaccines that could benefit from this technology.”
The Navy will test the system for effectiveness in delivering its vaccine for Dengue fever, a virus transmitted by mosquito that infected military personnel during World War II and the Vietnam War, and which has caused epidemics in Somalia and Haiti, and other tropical areas.
“DNA vaccines are a very promising technology, but for a better response you need a better delivery [method],” says Curtis Hayes, PhD, director of the infectious disease directorate at NMRC. “Currently, there are no vaccines being used in the field, just personal prevention, like bug spray. We have tested other vaccines that did not produce a strong response. This approach may induce a more vigorous response.”
Electroporation involves the use of brief electrical pulses to temporarily permeabilize cell membranes, which allows various types of molecules, such as DNA and proteins, to enter the cell more efficiently.
The center plans to perform trials on primates challenged with the virus after immunization. Hayes expects the trial to start in about six months. Yet, it may take more than a year until the vaccine can be used because the researchers will need to evaluate the longevity of immune response. If successful, the approach could be adopted by the malaria group at NMRC, he says.
“The Navy has many different vaccine candidates that they want to try to deliver in the muscle,” says Iacob Mathiesen, PhD, CEO of Inovio. “One problem with intramuscular delivery is that the efficiency of gene transfer is quite low. If you inject DNA dissolved in saline, only a few cells will take up the gene and express it. Some people think that this might be the reason why the immunization is quite inefficient and that you don't get the desired effect.”
Inovio's system is specially designed for getting improved transfection of skeletal muscles. “We use very brief electrical pulses in combination with injection,” says Mathiesen. “We apply these pulses at the site of DNA injection, which does something to the membrane that improves the uptake of the DNA and thereby the expression.” The pulses create some slight damage to the muscle tissue, which may also help to facilitate the immune response, he says, but the body repairs the damage over time.
The electrical pulse system has been used for anticancer drug delivery, but is new to skeletal muscle or gene delivery in humans, says Mathiesen. “We do know it works quite well in animals. When compared to injections without pulsing, we see that we improve the efficiency about 100-fold with much less variability. The amount of DNA used can also be reduced significantly.”
“Working with the Navy is important to us because it enables us to generate important primate data,” says Mathiesen. “If it works well, we can expand our collaborations. We hope more organizations will be interested in working with us to deliver their vaccines. There are many different vaccines that could benefit from this technology.”
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