Dr. David B. Weiner (born 1955)

2020 (est), Dr. David Weiner of The Wistar Institutehttps://wistar.org/our-scientists/david-weiner2022-wistar-org-our-scientists-david-weiner-profile-img.jpg

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ASSOCIATIONS

https://wistar.org/our-scientists/david-weiner

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David B. Weiner, Ph.D.

LABORATORY : The Weiner Laboratory

[ ...]

Director, Vaccine & Immunotherapy Center

W.W. Smith Charitable Trust Professor in Cancer Research, Immunology, Microenvironment & Metastasis Program, The Wistar Institute Cancer Center

ABOUT THE SCIENTIST

Professor Emeritus at the University of Pennsylvania School of Medicine.

Weiner directs a translational molecular immunology research team focused on creating novel immunotherapy approaches for disease prevention and treatment using synthetic nucleic acid technology. Accomplishments of the team and collaborators include the first clinical studies of DNA vaccines, with a focus on advances in gene optimization and electroporation (EP)-mediated DNA delivery. Their work has revitalized the field, rapidly and safely moving new advances into human studies. These include the world’s first Zika vaccine, the first MERS vaccine, an advanced Ebola Vaccine, and a novel HIV vaccine, among others. Additionally, the Weiner laboratory has helped to develop immunotherapy approaches that are currently in clinical testing for HPV-associated cancer, prostate and other cancers. The first clinically efficacious therapeutic DNA vaccine for HPV cervical intraepithelial neoplasia CIN) has moved into a licensure trial (REVEAL). Weiner and his lab have received several awards/honors for their accomplishments, including the Vaccine Industry Associations Outstanding Academic Research Laboratory (2015 & 2016), being named one of the Top 20 Translational Research Laboratories of the Year (Nature Biotechnology 2016, 2017 & 2018) and the 2014 Stone family Award for Cancer Research. Weiner was named one of the nation’s top 40 most influential vaccine scientists in 2014, received the 2011 NIH Directors Translational Research Award and is an elected fellow of the American Association for the Advancement of Science since 2011 and a fellow of the International Society for Vaccines, for which he served as president from 2018 to 2020. Weiner is an avid trainer, advisor and advocate for students, fellows and junior faculty as he is highly committed to developing the careers of young scientists.

Weiner received his B.S. in biology from Stony Brook University, N.Y., and his M.S. in biology from the University of Cincinnati. He then earned a Ph.D. in developmental biology with a focus on molecular immunology from the University of Cincinnati, College of Medicine. Weiner joined the University of Pennsylvania as a research fellow in the Department of Pathology and Laboratory Medicine, where he rose through the ranks to become Professor. He held a second appointment from The Wistar Institute from 1990 to 1993. At Penn, he served as co-chair of the Tumor Virology Program of the Abramson Cancer Institute and as chair of the Gene Therapy and Vaccine Training Program.

Prabook (Dec, 2021) - Saved page for "Dr. David B. Weiner"

Source : [HW008G][GDrive]

Born : December 2, 1955 in Brooklyn, New York

Background

Weiner, David B. was born on December 2, 1955 in Brooklyn. Son of Sy J. and Myrna G. Weiner.

Education

Bachelor of Science, State University of New York, Stony Brook, 1978; Master of Science, U. Cincinnati, 1985; Doctor of Philosophy, U. Cincinnati, 1986.

Career

Immunology research fellow division immunology School Medicine, University of Pennsylvania, 1986-1988; associate instructor pathology, University of Pennsylvania, 1987-1988; research assistant professor pathology, research assistant professor medicine, University of Pennsylvania, 1988-1989; assistant professor medicine, University of Pennsylvania, 1989-1990; assistant professor, director biotechnology, University of Pennsylvania, 1989-1990; Adjunct Professor pathology, University of Pennsylvania, since 1990. Lecturer various organizations and meetings.

Achievements

  • David B. Weiner has been listed as a noteworthy Pathology educator by Marquis Who's Who.

Connections

  • Married Abby I. Phillipson, August 22, 1981. Children: Rebecca, Lindsey.

  • Father : Sy J. Weiner

  • Mother : Myrna G. Weiner

  • Spouse : Abby I. Phillipson [ married August 22, 1981 ]

  • child : Lindsey Weiner

  • child : Rebecca Weiner


A few minutes with ... Dr. David Weiner of the Wistar Institute

Dr. David Weiner of the Wistar Institute in Philadelphia.

    • By John George – Senior Reporter, Philadelphia Business Journal

    • 5 years ago

    • When the Food and Drug Administration approved Blue Bell-based Inovio Pharmaceutical’s application last month to begin the first phase-I human clinical trial for a Zika vaccine, one of the people celebrating was Dr. David B. Weiner, executive vice president and director of the vaccine center, at the Wistar Institute in Philadelphia. Weiner discussed the role he and his team at Wistar played in the development of the experimental vaccine.
      How did Wistar get involved with Inovio and GeneOne on the development of a potential Zika vaccine? I have worked with Inovio Pharmaceuticals and their collaborator GeneOne Life Science for several years to develop DNA vaccine technology focused on cancers and infectious diseases. Our successes — most recently in Ebola and MERS — formed the basis for realizing we as collaborators had a lot to contribute to the development of a vaccine for Zika virus.
      What has been Wistar’s specific role in the process? The Weiner Lab at the Wistar Institute is a leader in vaccine technology and synthetic design and brings decades of experience to the development of new vaccine candidates. In this Zika health emergency, the Weiner Lab and partners decided to take a shot at envisioning a vaccine and collaborate to push technology forward in the shortest possible time. We came into this knowing only that a pathogen existed and was causing birth defects. We had to use our successes in other areas for a reasoned approach to crafting protective immunity against Zika and develop a product that could be safely put into humans and create an immune response. The fact that we achieved this in such a short period of time shows the combined power of collaboration and this compelling synthetic vaccine technology.
      How has this collaboration differed from other partnerships between research institutions and private companies with which you have been involved? This collaboration moved rapidly. There were no tools, no models, no meaningful guidelines for Zika itself. Imagine what it would be like to create a vaccine from scratch and work together — through trial and error — using just our knowledge to assess good data and bad data, and asking the right questions when we hit roadblocks. We could do that because we have formed strong ties in the vaccine development community.
      What lessons can other researchers and companies learn from the Zika vaccine collaboration? Collaborations enable partners with diverse skill sets and capabilities to work seamlessly together for a single cause. They promote trust and alignment. As a team, we can envision our goals, set milestones, delegate responsibilities, compare data, review our mistakes, and collectively make good choices. Uniting Wistar’s research discovery with our partners’ drug development expertise is critical for advancing impactful discoveries.

https://www.bizjournals.com/philadelphia/blog/health-care/2016/07/a-few-minutes-with-dr-david-weiner-of-the-wistar.html

39699442

Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of a randomized, blinded, placebo-controlled, Phase 2 clinical trial in adults at high risk of viral exposure

Mammen P. Mammen Jr., MD1#, Pablo Tebas, MD3#, Joseph Agnes, PhD1#, Mary Giffear, BS1, Kimberly A. Kraynyak, PhD1, Elliott Blackwood, MS1, Dinah Amante, BS1, Emma L. Reuschel, PhD2, Mansi Purwar, PhD2, Aaron Christensen-Quick, PhD1, Nieman Liu, MS1 Viviane M. Andrade, PhD1, Julie Carter, MPH1, Gabriella Garufi, PhD1, Malissa C. Diehl, PhD1, Albert Sylvester, MS1, Matthew P. Morrow, PhD1, Patrick Pezzoli, BS1, Abhijeet J. Kulkarni, MS2, Faraz I. Zaidi, MS2, Drew Frase, MS2, Kevin Liaw, PhD2, Hedieh Badie, PhD1, Keiko O. Simon, PhD1, Trevor R.F. Smith, PhD1, Stephanie Ramos, PhD1, Robert Spitz, MD4, Robert J. Juba, MSCEP1, Jessica Lee, MPH1, Michael Dallas, PhD1, Ami Shah Brown, PhD1, Jacqueline E. Shea, PhD1, J. Joseph Kim, PhD1, David B. Weiner, PhD2, Kate E. Broderick, PhD1, Jean D. Boyer, PhD1, Laurent M. Humeau, PhD1$

https://www.medrxiv.org/content/10.1101/2021.05.07.21256652v1.full.pdf



EVIDENCE TIMELINE

1994 (Nov 08) - NYTimes : "New Techniques Hold Promise in Fighting AIDS"

By Warren E. Leary / Nov. 8, 1994 / [HN01UJ][GDrive]

Scientists are looking at promising new approaches for combating the AIDS virus by undermining the processes controlling its reproduction and activation in the body.

A discovery that a cancer drug may block replication of the human immunodeficiency virus (H.I.V.), which causes AIDS, and the finding that a protein from the virus affects latency of the disease in the body after infection could lead to ways of controlling AIDS without directly attacking the virus, according to new research reports.

Researchers at the National Cancer Institute, reporting in the current issue of the journal Science, said that in laboratory tests, the drug hydroxyurea, which has been in use for 30 years, blocked reproduction of the virus in several types of infected cells.

In addition, the researchers said, hydroxyurea used in combination with the anti-AIDS drugs DDI and AZT significantly enhanced their effect in blocking viral reproduction, raising the possibility that lower doses of these compounds might be used, decreasing the risks of adverse side effects.

Scientists said the proposed treatment would not cure AIDS or eliminate H.I.V. from a patient's body. But it might bring the virus under control by blocking or slowing its replication in cells, holding the disease in check, they said. Researchers cautioned, however, that so far they had only test-tube results. They noted that some other potential AIDS treatments that had looked promising in laboratory cell studies did not work well in humans.

Dr. Franco Lori, the lead researcher in the drug study, said in an interview that because doctors had so much experience with hydroxyurea, animal tests probably would not be required before trying the new therapy on patients infected with H.I.V. Based on earlier published work by his team on the theory, he said, a human clinical trial of this use of the drug has been announced in France, and others are being considered in Italy, Germany and elsewhere.

Most research aimed at developing H.I.V. treatments focuses on finding compounds that assault the virus directly or on ways of enhancing the body's immune system to attack it, Dr. Lori said. But because the virus mutates so readily, these treatments often quickly lose their effectiveness, he said.

"We should examine the idea that fighting the virus like gentlemen, facing it head on and attacking it directly, is not the way to go," he said. "We should stop to think of new ways to fight, looking for more indirect ways of controlling the virus that it can't adjust to. Our work is along those lines."

The researchers found that hydroxyurea inhibited the synthesis of deoxynucleotides, the building blocks of DNA, by blocking a cellular enzyme. While some viruses can make this necessary enzyme themselves, H.I.V. cannot and instead must use enzymes found in the cells it invades to replicate, or duplicate, itself. White blood cells that are principal targets of the virus can either be quiescent cells, which make up 90 percent of the total, or active, reproducing cells, which make up less than 10 percent of the total. H.I.V. will replicate only in active cells, not quiescent ones, scientists found.

Dr. Lori said his group, which included Dr. Andrei Malykh, Dr. John N. Weinstein and Dr. Robert C. Gallo, a noted AIDS researcher, found that quiescent cells had low levels of deoxynucleotides, the foundations of DNA synthesis. To produce in active cells the conditions that occur naturally in quiescent ones, the researchers used hydroxyurea to reduce levels of deoxynucleotides. This, they said, essentially forced the H.I.V. into a state of hibernation, preventing it from replicating.

Decreasing the amount of deoxynucleotides in cells increased the uptake and metabolism of synthetically produced chemicals that closely resemble them, which include the drugs DDI and AZT, the researchers reported. This enhanced the effect of these compounds, they said, allowing the combination treatment of hydroxyurea and each of these drugs to block H.I.V. replication completely at lower, less toxic doses than if used alone.

The combination of hydroxyurea and DDI proved several times more potent than the pairing of hydroxyurea and AZT, the researchers noted, making the former combination the preferred option in human tests.

Hydroxyurea has been used for decades to treat human cancers, particularly myelogenous leukemia and a rare blood disease called polycythemia vera. The major adverse effect of the drug is suppression of blood-producing bone marrow at high doses. Several years ago, hydroxyurea was found to be a potential treatment for sickle-cell disease and thalassemia, which are inherited blood disorders. A five-year, multicenter trial of the drug as a sickle-cell treatment is nearing completion and researchers say initial results look promising.

In another study, scientists at the University of Pennsylvania Medical Center in Philadelphia said they have discovered that a protein from the virus regulates its latency in infected cells. Following infection with H.I.V., people usually enter a period of several years during which the virus lies dormant in most tissues of the body and causes no apparent disease.

In a report being published on Tuesday in The Proceedings of the National Academy of Sciences, Dr. David B. Weiner, along with a graduate student, David N. Levy, and others said an H.I.V. gene called Vpr produced a protein that stimulated cells infected with the virus to help it proliferate. In laboratory tests, the researchers reported that the Vpr protein activated viral replication in five latently infected cell lines and in fresh human blood cells isolated from infected patients.

Further tests showed that antibodies against the viral protein neutralized its activity in test tubes, the report said, suggesting that this might also be possible in the body.

"We've identified a function of the Vpr protein, a biological function that affects host cells, that is novel and interesting," Dr. Weiner said in an interview. "This is the first time we've found that one function of the virus is to regulate its own latency."

Researchers previously believed that this latent period was controlled by factors in the infected person's body, Dr. Weiner said, such as the immune system fighting to hold the virus in check. It has also been previously reported that certain human growth-factor hormones can stimulate a latent H.I.V. infection, he said.

The more active the virus is in replicating and spreading, the more Vpr protein it produces, he said, triggering more antibodies. These Vpr antibodies may eventually form the basis of new tests to both diagnose H.I.V. infections and gauge their progress, he said.

"What is really important about this finding is that, in addition to defining a new regulatory loop of the virus, it gives us a new target for drug development," Dr. Weiner said. "It tells us that anti-Vpr therapies are likely to have some benefit."

1997 (April 30) - NYTimes : "Vaccine Protects Two Chimps From AIDS "

Source : [HN01UK][GDrive]

A novel vaccine has protected two chimpanzees that were deliberately injected with the AIDS virus, scientists said today.

The experiments involved a vaccine made by incorporating weakened genes from H.I.V., the virus that causes AIDS. The experimental vaccine, which is based on DNA, is also being tested on humans, but it is too early for any meaningful results, said Dr. Anthony S. Fauci, the head of the National Institute of Allergy and Infectious Diseases.

Many vaccines and other therapies that work in animals fail in humans, and it is far from certain that scientists yet possess the knowledge to develop an effective AIDS vaccine for humans.

The authors of the chimp study injected large amounts of H.I.V. into the animals. Tests showed that the virus could be detected only once and in very small amounts during a 48-week monitoring period. In comparison, large amounts of H.I.V. were continually detected in another chimpanzee that received a different, weaker vaccine, the team of authors, led by Dr. David B. Weiner of the University of Pennsylvania, report in the journal Nature Medicine.

''The good news is that we are making another step toward broadening the spectrum of different vaccine concepts that might ultimately be proven effective in human clinical trials,'' said Dr. Fauci, whose agency helped pay for the research.

But he added, ''The news that is not so exciting is that we have seen protection in chimps before with other concepts for an AIDS vaccine and still do not have an effective vaccine for humans.''

The virus injected into the vaccinated chimpanzees is ''a weak one,'' the study did not determine what component of the immune system might be protecting the chimpanzees, and the number of animals and the type of immune responses were too small ''to make you say, 'Wow, this is significantly different from the others,' '' Dr. Fauci said.

Scientists say it is important to identify the specific immune factors that might provide protection against infection with H.I.V. because such knowledge can be used to determine the effectiveness of vaccines in human trials. More than a dozen experimental AIDS vaccines have been tested in a small number of people in this country. Among them is one genetically engineered from a weakened form of the canary pox virus.

The experimental vaccine in the chimp experiments differs from most standard viral vaccines, which are derived from either dead or weakened viruses.

As part of the broad vaccine effort, the DNA-based vaccine is also being tested in about 30 humans at the University of Pennsylvania in Philadelphia and the National Institutes of Health in Bethesda, Md.

Before any vaccine or drug can be marketed, it must pass the Food and Drug Administration's rigorous testing system, a process that usually takes years. The DNA-based vaccine is being tested in very small doses -- far lower than those in a standard vaccine -- to determine how well it is tolerated by the body and to study the degree and variety of reactions it produces in the immune system.

DNA vaccines are based on research that startled scientists when they learned about seven years ago that injection of naked genes into muscle could lead to production of proteins, a finding that countered the thinking of the time. Hoping that the finding might lead to a new approach to developing safe, inexpensive and effective vaccines, scientists are trying to develop DNA vaccines against infection with influenza, herpes and other infectious agents.

Like several other experimental AIDS vaccines, the one Dr. Weiner's team used is being tested in two ways. One is among uninfected individuals to determine whether it can prevent infection. The other is among infected patients to determine whether it can slow the progression of infection.

The University of Pennsylvania experiment involved four chimpanzees, three of which received the experimental vaccine. To test the vaccine's effectiveness, the scientists injected 250 times the amount of AIDS virus that is needed to produce infection into two of the three immunized chimpanzees. The third chimp, which acted as a control, did not receive an injection of the virus.

Using a test that can detect as few as 50 copies of virus per milliliter of blood, the scientists found the virus in the two protected animals, but only once. In one animal, it was in the sixth week after the virus was injected; in the other animal, it was in the eighth week. The virus could not be detected at other times, indicating significant protection.

The fourth chimpanzee received an inoculation that did not contain genetic material from the AIDS virus. Tests showed 10,000 copies of H.I.V. in that chimpanzee.

In an editorial in the same issue of Nature Medicine, Dr. Ronald C. Kennedy of the University of Oklahoma wrote that he was guardedly optimistic about the prospects of a human AIDS vaccine. But Dr. Kennedy said it was not clear why Dr. Weiner's chimpanzee experiment succeeded when an earlier one by other researchers failed.

2020 (June 13) - NYTimes : "Guaranteed Ingredient in Any Coronavirus Vaccine? Thousands of Volunteers"

By Heather Murphy / Published June 13, 2020Updated June 22, 2020 / Source : [HN01UL][GDrive]

Picture : "Two sisters in Missouri were among the first to have an unproven coronavirus vaccine injected in their bodies. If it makes it to market, it would also be the first DNA vaccine for any disease. Heather Wiley, left, and Ellie Lilly outside Ms. Wiley’s home in Independence, Mo. “I’m not a health care worker; I’m not an essential worker,” Ms. Wiley said of joining a vaccine trial. “But I’m healthy, so I can do this.”"[HN01UM][GDrive]

Not long after researchers completed their work with mice, guinea pigs, ferrets and monkeys, Human Subject 8, an art director for a software company in Missouri, received an injection. Four days later, her sister, a schoolteacher, became Subject 14.

Together, the sisters make up about 5 percent of the first ever clinical trial of a DNA vaccine for the novel coronavirus. How they respond to it will help determine the future of the vaccine. If it proves safe in this trial and effective in future trials, it could become not only one of the first coronavirus vaccines, but also the first DNA vaccine ever approved for commercial use against a human disease.

Hundreds of experimental vaccines for the new coronavirus are currently being developed across the world. These vaccines’ ability to advance will depend not only on science and funding, but also on the willingness of tens of thousands of healthy people to have an unproven solution injected into their bodies.

In many of these studies, the vaccine recipe isn’t the only thing on trial. Gene-based vaccines — and at least 20 coronavirus vaccines in development fall into this category — have yet to make it to market. Should one end up in doctors’ offices amid the rush to shield billions from Covid-19, it would represent a new chapter for vaccine development.

And though vaccine research has never moved this quickly — potentially meaning enhanced risks for volunteers — it has never been easier to recruit subjects, according to Dr. John E. Ervin, who is overseeing the DNA vaccine trial at the Center for Pharmaceutical Research in Kansas City, Mo., in which the sisters are involved. For the Phase 1 trial of the vaccine, which was developed by Inovio Pharmaceuticals, 90 people applied for the 20 slots in Kansas City.

“We probably could charge people to let them in and still fill it up,” he said. (In fact, the participants were paid per visit.)

The art director, Heather Wiley of Independence, Mo., said that realizing she would make around $1,000 for her participation was a bonus, not her primary motivation.

“I’m in the middle of the country trying to process 100,000 dead and how all those people died alone,” she said. Her fears for her family left her so anxious she couldn’t sleep.

While looking up vaccines, she stumbled on Dr. Ervin’s trial, which was recruiting volunteers just 20 miles from her. Two months shy of 50 and healthy, she qualified.

Step 1: A shot with computer-engineered DNA

Two weeks later, Dr. Ervin was injecting Ms. Wiley just beneath the skin of her upper arm with a transparent liquid containing the experimental vaccine.

The solution contains a computer-engineered DNA sequence, which includes genetic instructions for building the spike that makes the coronavirus so superb at entering its host’s cells. Cells are equipped to read genetic instructions; that’s just part of what they do. When these instructions arrive, the cells follow them and make the very same spike protein present on the surface of the coronavirus now wreaking havoc on the world.

The immune system responds to these spike proteins, now being manufactured by the body, and mounts a defense. These spike proteins are harmless; they are not attached to a virus. But the hope is that in the future, should a virus wearing spikes with that same genetic code attempt to invade, the immune system’s arsenal would be prepared.

[Inovio Pharmaceuticals, Incorporated] researchers engineered the vaccine in just three hours, according to Kate Broderick, the company’s senior vice president for research and development. Or, rather, their computer algorithm did: On Jan. 10, when Chinese researchers released the genetic code of the novel coronavirus, the team ran the sequence through its software, which popped out a formula.

This timeline struck some in the financial sector as too good to be true. Citron Research, which advises investors on companies to bet on, called Inovio “the Covid-19 version of Theranos,” referring to the blood-testing device company that imploded as its supposedly revolutionary product was revealed to be a hoax.

“Much like Theranos, Inovio claims to have a ‘secret sauce’ that, miraculously, no pharma giant has been able to figure out,” Citron Research wrote. “This is the same ‘secret sauce’ that supposedly developed a vaccine for Covid-19 in just three hours.”

There are several reasons that vaccine scientists are skeptical that we will ever see a DNA vaccine for the coronavirus. But speed is not one of them.

“That’s the beauty of these DNA vaccines,” said Wolfgang W. Leitner, the chief of the innate immunity section at the National Institute of Allergy and Infectious Diseases. “They are simple and fast in terms of development.”

Nor are vaccine scientists concerned about the supposed “secret sauce.” In fact, it’s quite the opposite: They are skeptical precisely because the technology behind DNA vaccines has been around for decades and has been applied toward so many infectious diseases — H.I.V., the flu, malaria — yet none of the vaccines have made it to market.

They believe that this approach is capable of producing immunity. Already, DNA vaccines have been licensed for use in pigs, dogs and poultry. But the big if, according to Dr. Dennis M. Klinman, a vaccine scientist who worked at the Food and Drug Administration for 18 years, is whether one will ever be able to generate strong enough an immune response in humans.

Step 2: A series of zaps to ‘steer the DNA’

Even though Ms. Wiley had read the packet on the science of it all, the next step felt like entering uncharted territory.

Shortly after the initial injection, a nurse handed Dr. Ervin a device resembling an electric toothbrush. He pressed the head — which contains three tiny needles instead of bristles — over the raised skin on her arm, where she’d just had a shot. Then he zapped her.

“It was not painful, but it’s unlike anything I’ve ever experienced,” Ms. Wiley said.

The carefully calibrated electrical pulses “basically steer the DNA” into the cells by briefly opening up pores in their membrane, according to [Dr. David B. Weiner (born 1955)], the director of the vaccine and immunotherapy center at the Wistar Institute and an adviser to Inovio.

Although it may sound fantastical, the technology, called electroporation, dates to the 1980s, when a similar approach was first used to make transgenic plants, according to Dr. Leitner.

Phase 1 trials are focused on safety. As a whole, DNA vaccines are known to be very safe, Dr. Klinman has written. Early fears — that they might change a person’s DNA, for example — were proved unfounded long ago.

But there is still no way to know how subjects will respond to the new formula or how the new approach to administering the vaccine will go over. When Dr. Ervin used a different electrical pulse system in an Ebola DNA vaccine trial in 2018, “Boom! They were ready to jump off the table,” he said, adding that he wished he could have paid the subjects extra. (Dr. Ervin runs trials for many biotech companies and is not involved in deciding dosages or implementation methods. His job is to follow the company’s instructions and report back, he said.)

Step 3: Wait for side effects

Ms. Wiley spent the next couple of hours after her injection watching “The King’s Speech” as researchers monitored her for an adverse response. But she felt only relief at being useful in some way.

“I’m not a health care worker; I’m not an essential worker,” she said. “But I’m healthy, so I can do this.”

Soon her sister Ellie Lilly, 46, a seventh-grade history teacher in Lee’s Summit, Mo., had enrolled as well.

Throughout a Phase 1 trial, the newest subjects receive larger doses than participants who started earlier. Ms. Lilly, who entered the trial as Subject 14 four days after her sister, learned that she would be receiving twice as many shots and zaps. Still, the pulses didn’t hurt. “It just feels strange,” she said.

By the time Ms. Lilly got home she felt exhausted and a little nauseous, she said. She told a nurse who called to check in that she wasn’t sure if that was a function of the vaccine or an emotional day. Either way, she felt well enough the following day that her husband wanted to enroll. (He was rejected.)

Four weeks after their first injections, the sisters returned for their second and final doses.

Step 4: Wait to see if it’s deemed safe, and whether it actually did anything

The first hint of whether anyone in the trial developed the coveted antibodies, which would suggest that the vaccine might be helping the immune system, won’t come until Inovio releases that data later this month. That report will include findings from both the Kansas City trial and a simultaneous trial of 20 volunteers in Pennsylvania. This data will influence whether the vaccine dies in the first stage, as most vaccines do, or whether it moves on.

The Phase 1 trial has already been expanded to include older patients at a third location. If everything goes as hoped, the F.D.A. has granted the company permission to start testing effectiveness in the community, according to Inovio.

At that point, researchers would inject thousands of people with the vaccine and thousands more with a placebo. No one would be intentionally exposed to the coronavirus, but by studying rates of infection of the two groups, the researchers could draw conclusions about the effectiveness of the vaccine.

The sisters are rooting for the Inovio vaccine. But, “even if it doesn’t work, we’re still a piece of the research,” Ms. Lilly said.

Ms. Lilly knows that the chances are low that her two experimental doses will protect her, but she can’t help hoping. Come fall, she is headed back to the classroom, where it feels inevitable that sooner or later, she too will be exposed to this tiny but powerful virus.

2020 (June 26) - Philadelphia Inquirer : "Coronavirus could be the turning point for a vaccine technology 30 years in the making: The coronavirus is rekindling excitement about genetic vaccine technology, even though it has yet to yield an approved immunization."

Mentioned : Dr. David B. Weiner (born 1955) / Inovio Pharmaceuticals, Incorporated /

[Dr. David B. Weiner (born 1955)] is known in scientific circles as “the father of DNA vaccines.” The tag pays homage to his pioneering work over 30 years, but it’s also a reminder that his baby is still aborning.

Not a single human DNA vaccine has made it to market anywhere in the world, and the technology is still rapidly evolving.

The pandemic may be the moment of truth. Genetic code vaccines — built with DNA or RNA — are strong front-runners in the global race to develop an immunization against the coronavirus that has claimed nearly half a million lives worldwide since it emerged in China seven months ago.

[Inovio Pharmaceuticals, Incorporated] — the Plymouth Meeting biotech that Weiner cofounded, advises, and has financial interests in — was recently dissed as “under-the-radar” in industry press. But in March, the company’s DNA vaccine for the coronavirus was featured on TV’s 60 Minutes. And last week, the company snagged a $71 million government contract to manufacture the skin-zapping device that is part of its vaccine platform.

Within days, Inovio says, it will announce results of the first small human trial of its coronavirus vaccine, “INO-4800.” Initial testing focuses on safety, but that shouldn’t be a problem, based on Inovio’s other experimental DNA vaccines.

The big question is whether the shots generated signs of a potent immune response. Feeble responses — too wimpy to protect against infection — have been the Achilles’ heel of DNA vaccines.

[Dr. David B. Weiner (born 1955)], 63, is acutely aware that getting a vaccine approved is about managing expectations, cultivating good press, and raising money — as well as solid science. He said that the vaccine race is against the virus, not rival developers. That multiple vaccines using varying strategies are needed. And that perfect is the enemy of the good.

“I think we should set our expectations low,” he said. “I really think we’re most likely to have several vaccines, and that they will lower disease severity and prevent some infections. It doesn’t have to be 100% effective to have enormous value for the world.”

Fast-tracked

It normally takes a decade or two to get a vaccine from concept to clinic, yet the aim is to start immunizing people against the new coronavirus, SARS-CoV-2, by next summer. More than 120 vaccine candidates using five different strategies are advancing at a breakneck pace, aided by billions of dollars from governments and philanthropies such as the Gates Foundation.

Among the developers already conducting human testing are four with RNA platforms: Moderna, Pfizer, CureVac, and Imperial College London. [Inovio Pharmaceuticals, Incorporated] is the only front-runner with a DNA-based vaccine.

All vaccine approaches involve teaching the immune system to recognize a virus’ unique proteins, or antigens. If the real microbe tries to invade — and viruses have to hijack living cells to replicate — immune cells are primed to attack.

Tried-and-true vaccine technologies involve growing a weakened or inactivated virus in eggs or animal cells, then extracting and purifying the desired antigens. It’s an arduous, time-consuming, costly process.

In the early 1990s, [Dr. David B. Weiner (born 1955)] and some others had an idea: Instead of injecting the antigen, why not inject the viral gene that carries instructions — DNA — for making it? DNA would transfer the instructions to RNA in the cell’s molecular machinery, which would then produce the antigen to ward off infection.

The beauty of the approach was obvious from the beginning. DNA is a sequence of chemicals, called nucleic acids, that can be rapidly synthesized and fused together in the lab.

Consider that after Chinese researchers published the coronavirus’ entire genetic code in January, Inovio scientists “printed” their vaccine in a matter of hours with a DNA synthesizer. Like almost all developers, they used the code for the “spike” protein, which makes the stud-like projections that the coronavirus uses to latch onto and sneak into cells. But while the advantages of using DNA were clear, so were the challenges.

Nature instructs

Weiner was a professor of medicine and a researcher at the University of Pennsylvania in the 1990s when he pioneered the technology for delivering the DNA into cells.

Decades earlier, researchers had discovered that bacteria carried strange little loops of DNA that were separate from their chromosomal DNA and could replicate independently. Some of these “plasmids” were found to help bacteria resist antibiotics.

Weiner’s lab synthesized and equipped plasmids to carry viral antigen genes into human cells.

“We look for nature to teach us what to do,” said Weiner, who is now emeritus at Penn and vice president of Wistar Institute, which is collaborating on Inovio’s vaccine.

In 1997, Weiner’s team reported a breakthrough: Their novel vaccine had protected two chimpanzees from the virus that causes AIDS. (Fun fact: Weiner and his lab had a cameo in Philadelphia, the 1993 movie about HIV/AIDS and homophobia that earned Tom Hanks an Oscar.)

Ami Patel, research assistant professor, and David B. Weiner, director of Wistar Institute's vaccine and immunotherapy center, working on his synthetic DNA vaccine technology, the basis for an experimental coronavirus vaccine. Wistar Institute.[HN01UH][GDrive]
David B. Weiner, shown in his Wistar Institute lab with research assistant professor Ami Patel, believes several types of vaccine will be needed to curb the coronavirus pandemic.The Wistar Institute[HN01UI][GDrive]

In humans, however, DNA vaccines simply weren’t very effective. At the injection site, uptake of plasmids by skin and muscle cells was nominal and unpredictable. When the cells produced antigen, it triggered a tepid response by the first line of immune defense — namely, antibodies. But few plasmids found their way into “antigen-presenting cells,” which are essential for activating the more powerful second line of defense — T cells. “Killer” T cells can destroy virus inside as well as outside of cells, and “memory“ T cells remember the invader to prevent future infections.

By 1999, when Weiner wrote about DNA vaccines in Scientific American, the best he could say was, “Preliminary findings hint that useful immune responses can be achieved.”

He soldiered on with a team that included graduate student Joseph Kim, now president, CEO, and cofounder of Inovio.

“A lot of big boys and girls left the field,” Kim said, referring to giant pharma companies that abandoned DNA vaccine research. “One who persisted, by conviction or stubbornness or both, was [Dr. David B. Weiner (born 1955)].”

Among the “optimization” measures: The plasmids were engineered to carry additional genes that made cells produce natural immune-boosting substances, including one that stimulated proliferation of the important antigen-presenting cells. To get better uptake of the plasmids, the vaccine was delivered along with electrical charges that briefly opened pores in cell membranes near the injection site.

Manufacture of that handheld “electroporation” device — a proprietary, battery-operated gizmo now named Cellectra — will be scaled up using $71 million from the U.S Department of Defense.

Dark horse or front-runner

RNA vaccine technology, which is also about 30 years old, has a different set of pros and cons. Messenger RNA doesn’t need a plasmid because it doesn’t have to get into the cell’s nuclear DNA to work. But single-stranded RNA is far less stable than double-stranded DNA. Enzymes in the body can quickly degrade RNA, which cuts antigen production. The vaccine has to be kept refrigerated or frozen.

The instability problem is like “buying fruit that spoils in a few minutes,” said [Dr. David B. Weiner (born 1955)], adding that he is biased.

Inovio can be seen as a dark horse in the vaccine race — or an odds-on favorite.

None of its prospects has crossed the finish line. Its Ebola and Zika vaccines had to be abandoned because as the outbreaks waned, so did funding and the number of potential clinical trial subjects.

On the other hand, Inovio has 15 vaccines in clinical testing for cancer as well as infectious diseases. The company is expanding human testing of its vaccine for Middle East Respiratory Syndrome (MERS) — caused by another coronavirus — because it generated strong antibody and T-cell responses in most participants in an initial trial.

“It’s going to take many technologies crossing the finish line to make an impact in the face of SARS-CoV-2,” Weiner said, “and we hope our technology can be part of the solution.”