Revealing the Immunogenicity of a SARS-CoV-2 DNA Vaccine Candidate

Inovio INO-4800 is a DNA vaccine candidate matched to the coronavirus causing COVID-19 disease in humans

dna strand with light on it

The Wistar Institute in Philadelphia announced a study reporting initial immunogenicity of a synthetic DNA vaccine for SARS-CoV-2 coronavirus.

The vaccine candidate, INO-4800, advanced to phase 1 clinical testing in just 10 weeks after receipt of this novel virus information.

No preventive vaccines are currently approved and the U.S. government, as well as many others, has made the development of a preventive vaccine for SARS-CoV-2 coronavirus infections a top priority. 

Developed in collaboration with Inovio Pharmaceutical, Inc., and other scientists, and published in Nature Communications on May 20, 2020, this report focuses on immune studies in animals, which show induction of functional antibody responses and T-cell responses following immunization.

The viral genome became available on January 11, 2020, and the Wistar-Inovio team immediately began working to design and develop a new vaccine, based largely on their previous experience creating a synthetic DNA vaccine against the related coronavirus that causes Middle East respiratory syndrome.

Working with Inovio, a group led by David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center (VIC) and W.W. Smith Charitable Trust Professor in Cancer Research, focused on the rapid development of a synthetic DNA-based vaccine targeting the major surface antigen Spike protein (S) of SARS-CoV-2 into preclinical studies.  

“We focused on both assay development and vaccination studies to test if immune responses induced by the vaccine in laboratory animals were functional against the virus,” said Dr. Weiner in a related press release.

“Our focus was the induction of immune responses that could in concept make it difficult for SARS-CoV-2 to have a home in the human body,” said Dr. Weiner, co-senior author of the publication. 

“The vaccine was designed leveraging our synthetic DNA technology, which has a set of conceptual advantages including accelerated clinical development built on a conceptually safe, non-live, simple platform that has scalable manufacturing and temperature stability.” 

“The vaccine-induced antibodies in vaccinated animals were of sufficient quantity and quality to block the interaction of the virus with its receptor, which is its doorway into infecting the body, and were present in the lungs, a place where immunity is very important.” 

“The vaccine also induced T-cell function, which is critical for clearing viral infections from the body.” 

“These are indications that the immunity it induced might provide no escape for the SARS-CoV-2 virus. We are looking forward to additional studies and examining data from the ongoing clinical trial.”

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The team includes Wistar VIC investigators Daniel Kulp, Ph.D., Kar Muthumani, Ph.D., and Ami Patel, Ph.D., who is a shared first author in the paper.

DNA vaccines work by delivering the genetic information required to make a certain viral protein in the recipient’s body, which stimulates the immune system to recognize that protein as foreign and build a response against it, thus targeting the virus and providing protection from infection.

Expressed in vitro, INO-4800 induced robust expression of the S protein. 

Within days following a single immunization of mice and guinea pigs, the vaccine-induced antigen-specific T cell responses and functional antibodies that neutralize the virus, blocking the ability of the SARS-CoV-2 S protein to bind to the angiotensin-converting enzyme 2 (ACE2) host receptor on human cells.

Importantly, SARS-CoV-2-specific antibodies were detected in the lungs of immunized animals, suggesting they might protect against upper and lower respiratory disease that is associated with severe cases of COVID-19.

“While this candidate continues its journey as a potential vaccine against COVID-19, we are continuing our work in the lab to gather more information on the vaccine’s performance in small and larger animals,” said Patel, who is a research assistant professor at Wistar. 

“We will further characterize antibody functionality, cellular responses, and the ability of INO-4800 to mediate protection of animals against viral challenge.”

The SARS-CoV-2 coronavirus emerged in 2019 in China. On March 11, 2020, the World Health Organization declared a global pandemic.

Funding from the Coalition for Epidemic Preparedness Innovations. No conflicts of interest were disclosed.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. The Institute information is available at wistar.org.

Precision Vaccinations publishes SARS-CoV-2 vaccine development news.