- Inovio Pharmaceuticals has started Phase 1 testing of its experimental COVID-19 DNA vaccine in healthy volunteers.
- The U.S. biotech firm has already produced enough of the vaccine to support Phase 1 (immune system reactivity and safety) and Phase 2 (efficacy) testing and plans to have one million doses ready for distribution by the end of 2020.
- The experimental vaccine requires a special device that uses electricity to drive DNA into cells of the body.
Inovio Pharmaceuticals headquartered in Pennsylvania, has just begun Phase 1 human clinical trials of its new DNA vaccine for COVID-19 (INO-4800).1 Inovio’s experimental DNA vaccine uses an electrical device to deliver DNA directly into the cells of a person being vaccinated.2
The company’s Apr. 6, 2020 announcement of Phase 1 clinical trials stated: “Preclinical data, which have been shared with global regulatory authorities and submitted as part of the IND, have shown promising immune response results across multiple animal models. Additional preclinical trials, including challenge studies, will continue in parallel with the Phase 1 clinical trial.”3
In the U.S., the development, testing and licensing process for an experimental vaccine generally takes 15-20 years to complete,4 5 but there are calls to speed up the licensing process for COVID-19 vaccines.6 Drug companies in the U.S. and other countries are racing to fast track their experimental COVID-19 vaccines to market within 12 to 18 months or even sooner.7 If companies get an “emergency use” authorization from the Food and Drug Administration (FDA),8 Inovio’s DNA vaccine could be among those vaccines ready by the fall of 2020 to be distributed to health care workers and other groups considered to be at “high risk” for COVID-19 infections or complications.
Funded by Gates, CEPI, DOD with Wistar & Other Partnerships
Inovio’s COVID-19 vaccine research has been funded by a $5M grant from the Bill and Melinda Gates Foundation and a $9M grant from the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI).9 Inovio also has a partnership with Philadelphia’s Wistar Institute and Beijing Advaccine Biotechnology Co. in China to develop the vaccine.10 11
In addition, Inovio has a partnership with Ology Bioservices, Inc., headquartered in Florida. Ology and Inovio secured a $11.9M contract with the U.S. Department of Defense to provide the experimental DNA coronavirus vaccine for upcoming clinical trials and potential manufacturing of the vaccine for military personnel in the future. In a Mar. 24 press release issued by Ology and Inovio, Douglas Bryce, Joint Program Executive Officer for Chemical, Biological, Radiological and Nuclear Defense, said:12
Given the current global health crisis, prophylaxis/vaccine development is critical to defend against the coronavirus disease 2019. We need several approaches to ensure we have a quick solution, and the medical countermeasures Advanced Development and Manufacturing Facility is poised to contribute to the race for a vaccine in coordination with our interagency partners like Health and Human Services, along with our partners in industry and academia.
Healthy Volunteers Get Two Doses in Trials
Acceptance by the U.S. Food and Drug Administration (FDA) as part of their Investigational New Drug (IND) program allowed Inovio to move forward with enrolling 40 healthy volunteers from Philadelphia’s Perelman School of Medicine at the University of Pennsylvania and the Center for Pharmaceutical Research in Kansas City, Missouri.13 The first volunteers were injected with the experimental vaccine on April 5 and clinical trial participants each will be given two doses, four weeks apart.
The Phase 1 study is designed to evaluate immune system response and safety of Inovio’s DNA COVID-19 vaccine for use in humans. Preliminary data are expected by late summer and Inovio plans to immediately move on to Phase 2 studies to evaluate efficacy of the vaccine.
Inovio started working on its COVID-19 vaccine when the genetic sequence of the virus became available in early January 2020. The company has already produced thousands of doses of INO-4800, enough to supply both Phase 1 and Phase 2 studies. They plan to have one million doses of the vaccine available by the end of 2020, “for trials as well as emergency use, subject to regulatory guidance and funding.”14
In July 2019, Inovio announced positive results from a Phase 1 clinical trial testing of its experimental DNA vaccine for the Middle East Respiratory Syndrome (MERS),15 a new coronavirus infection that emerged in 2012. MERS is associated with a high mortality rate of 12 to 86 percent.16
The DNA Vaccine Difference
According to the National Institute of Allergy and Infectious Diseases (NIAID), “Traditional vaccines consist of entire pathogens that have been killed or weakened so that they cannot cause disease.” 17 Other vaccines developed in the late 20th century contain only microbe components, or antigens, that are thought to best stimulate an immune response and antibody production.
Licensed viral and bacterial vaccines that are in widespread use today are categorized as either killed inactivated, live attenuated, toxoid, or subunit vaccines. They contain antigens from lab altered viruses and bacteria, as well as adjuvants, such as aluminum or oil-in-water emulsion, to provoke stronger inflammatory responses for stimulating artificial immunity; preservatives, such as Thimerosal; stabilizers, such as MSG and gelatin; and residual substances from the manufacturing process, such as chemicals, antibiotics, human diploid cells, animal and insect cell proteins and other excipients. 18
However, for the past several decades, scientists have been experimenting with creation of nucleic acid vaccines which, according to NIAID, “involves introducing genetic material encoding the antigen or antigens against which an immune response is sought. The body’s own cells then use this genetic material to produce the antigens.”19 DNA vaccines like Inovio’s experimental COVID-19 vaccine (INO-4800) inject a small piece of circular DNA called a plasmid that carries genes encoding proteins from the pathogen (in this case, COVID-19) to provoke the cells into producing antibodies.
Writing in Biotech Primer, Emily Burke, PhD explained that, “the ‘visiting’ DNA prompts the host to produce the target viral protein and consequent immune response within their own cells, but without [causing] an infection. DNA vaccines try to stimulate the body’s cells to continue to reproduce the antigen. Burke commented on the difficulty of getting the body’s cells to accept injected DNA without further intervention and stated:20
The key challenge for DNA/RNA vaccines is getting patients’ cells to accept the introduced genetic material. So far, the most effective technique seems to be electroporation–delivering short pulses of electrical current to the patient with the vaccine. The electricity creates temporary pores in a patient’s cell membranes, enabling the DNA/RNA to enter.
DNA Vaccines: Gaps in Knowledge
DNA (and RNA) vaccines have been available and approved for veterinary medicine, but none have yet been approved for human use. Compared to traditional vaccines, nucleic acid (genetic) vaccines are less inexpensive and easier to manufacture because they consist only of DNA or RNA, which is taken up and translated into protein by host cells.21
The World Health Organization (WHO) acknowledges there are gaps in scientific knowledge about DNA vaccines and states:22
Many aspects of the immune response generated by DNA vaccines are not understood. However, this has not impeded significant progress towards the use of this type of vaccine in humans, and clinical trials have begun.
Some of the outstanding questions about DNA vaccine safety include:23
- chronic inflammation because the vaccine continually stimulates the immune system to produce antibodies;
- possible integration of plasmid DNA into the body’s host genome resulting in mutations;
- problems with DNA replication;
- triggering of autoimmune responses, and
- activation of cancer-causing genes.
Inovio’s Electric Device Delivery System Drives DNA Into Body Cells
On Mar. 12, 2020 Inovio announced it had received a $5M grant from the Gates Foundation to accelerate the testing and scale up of CELLECTRA® 3PSP proprietary hand held “smart device” running on batteries for the intradermal delivery of its DNA COVID-19 vaccine (INO-4800). The press release explained that electricity will be used to give people Inovio’s DNA vaccine in order to “open small pores in the cell reversibly to allow the plasmids to enter” so the “cell’s own machinery” can “generate coded antigens, which then stimulate an antibody response:”24
The next generation CELLECTRA 3PSP device is designed specifically for a COVID-19 type pandemic scenario. It is a small, portable, hand-held, user-friendly device that runs on readily available “AA” batteries… INOVIO’s DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO’s proprietary hand-held smart device called CELLECTRA®.
CELLECTRA® uses a brief electrical pulse to open small pores in the cell reversibly to allow the plasmids to enter, overcoming a key limitation of other DNA and mRNA approaches. Once inside the cell, the plasmids are used by the cell’s own machinery to generate coded antigens, which then stimulate an immune response, thereby strengthening the body’s own natural defense mechanisms. Administration with the CELLECTRA device ensures that the DNA medicine is delivered directly into the body’s cells, where it can go to work immediately mounting an immune response.
The company added that, “INOVIO’s DNA medicines do not interfere with or change in any way an individual’s own DNA.”