thevaccinereaction--2020-04-19--Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells

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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 Healthy Volunteers Get Two Doses @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 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 can not cause disease.
” 17 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ 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 ( and RNA ) vaccines have been available and approved for veterinary medicine , but none have yet been approved for human use @ @ @ @ @ @ @ 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 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 ; @ @ @ @ @ @ @ 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 @ @ @ @ @ @ @ response : ” 24 The company added that , “ INOVIO ’ s DNA medicines do not interfere with or change in any way an individual ’ s own DNA.
” Electroporation is defined as “ a process of applying a high-voltage electrical pulse to a living cell , causing temporary permeability of the cell membrane , through which a foreign material such as DNA may pass.
” 25 Over the past two centuries , electric fields have been used to kill microbes for food and water sterilization and , since the 1990s @ @ @ @ @ @ @ electroporation to temporarily destabilize cell membranes for the purpose of ( 1 ) fusing cells together through membrane destabilization ( electrofusion ) ; ( 2 ) introducing DNA material into cells through transient pores in the membrane ( electrogenethearpy ) ; and ( 3 ) delivering chemotherapeutic drugs directly into cells ( electrochemotherapy ) .
Irreversible electroporation uses a much higher electrical energy regime that induces cell death and is employed in certain types of therapies to treat cancer.26 27 In 2013 , researchers at Inovio and University of Pennsylvania division of Infectious @ @ @ @ @ @ @ ’ s CELLECTRA® adaptive constant current device helps enhance vaccine DNA uptake by cells and generates a “ more robust immune response : ” 28 The Inovio and University of Pennsylvania researchers noted that “ A primary drawback of electroporation ( EP ) is pain and discomfort at the application site compared with convention injections.
” In a small clinical trial , they evaluated the pain “ tolerability ” of the CELLECTRA® device by testing it on 10 healthy male adults given a sterile saline solution injection without any DNA , which was @ @ @ @ @ @ @ Inovio device .
Nine out of ten subjects experienced mild to moderate injection site reactions of pain , tenderness , redness and swelling .
There were also reaction reports of involuntary muscle contraction and mild to severe asymptomatic increases in CPK ( creatine phosphokinase ) levels in the blood of 6 participants .
According to Lab Tests Online , “ creatine kinase ( CK ) is an enzyme found in the heart , brain , skeletal muscle , and other tissues .
Increased amounts of CK are released into the blood when there @ @ @ @ @ @ @ acknowledged that “ The EP procedure has been shown to carry some potential of transient muscle damage in animal models , evident as increased numbers of fibers with central nucleoli and damaged myofibrillar bundles.
” At the end of the article , researchers discussed how EP could stimulate greater and longer lasting immune responses for experimental DNA vaccines being designed to prevent HIV and HPV .
Although the 10 healthy male adults in the Inovio and University of Pennsylvania study did not get injected with DNA , the researchers explained that:30