Key Summary

Limitations of vaccines for protection against COVID-19

One of the key countermeasures under development to protect people from SARS-Cov-2 (the virus that causes COVID-19 infection) is vaccination. Vaccines have the benefit of being widely distributable as a means of protection populations from disease. However, they have some key limitations for COVID-19 prevention. One of the main issues, is that they are dependent on the recipient’s immune system to develop a protective response against the coronavirus. Not everyone’s immune system has the same ability to mount a protective response after vaccination. This is particularly true of the elderly, who are one of the high-risk groups for COVID-19. Other groups that have trouble mounting a good immune response are infants, people who are immunosuppressed (like organ transplant patients) and people with certain diseases, like people with heart or lung disease. A second issue with using vaccines to create immune protection, is that establishing immunity takes time. It can be weeks before the level of immune response is adequate in some diseases. It is unknown how long it will take for people to mount protective immunity against SARS-CoV-2; successful vaccination may ultimately require multiple injections over time, like vaccines against hepatitis or human papillomavirus. Another limitation of infectious disease vaccines is that they are typically intended for protecting healthy people and do not have much effect if someone is already infected.
Not everyone’s immune system has the same ability to mount a protective response after vaccination.

SmartPharm Approach: Gene MAbs™ for Coronavirus

SmartPharm is applying our non-viral gene therapy platform to develop an effective preventive treatment for SARS-CoV-2. We are using DNA designed to produce in the muscle of the person who receives the gene a monoclonal antibody (“Gene Mab™”) that could be protective against the SARS-CoV-2 virus. To do this, we are utilizing a novel DNA vector with low immunogenicity, durable expression potential and cost-effective manufacturing up to millions of doses. We are coupling this type of DNA vector with a delivery system that significantly enhances DNA expression in the muscle and is also capable of high-volume, economic production. Coupled together, these represent a way to generate protective mAbs in many people to provide “pop-up immunity” in this population against COVID-19 regardless of their immune status or their infection status.

The first step in developing a Gene MAb™ against SARS-CoV-2 is to determine a mAb sequence that possesses both a high binding affinity to the coronavirus (so it stays attached to the virus for a long time) and the ability to neutralize the virus (block it from invading cells or attract immune response against the virus). We have implemented strategic partnerships with a number of organizations to do this, including Sorrento Therapeutics. Sorrento has initiated an accelerated program to identify potent neutralizing antibodies against SARS-CoV-2 that can be used for either treatment or prophylaxis. Based on this collaboration as well as internal work, SmartPharm will define a DNA that can express these antibodies in human skeletal muscle and use a delivery technology designed to allow the DNA to be delivered directly into the muscle. The SmartPharm delivery system is designed to be used with a standard hypodermic needle, the way most vaccines are delivered.

1. Antibodies with significant neutralizing efficacy against SARS-CoV-2 are identified in recovered COVID-19 patients. 2. The antibody is sequenced and incorporated into a DNA plasmid. 3. Plasmids are combined with a delivery system for a final formulation of the Gene MAb™ drug. 4. The Gene MAb™ is given to people using a standard hypodermic injection.

After delivery in the muscle, the DNA is designed to produce antibodies in the muscles within a matter of hours. Within a day or two—a much faster time than a typical vaccine—protective levels of antibody could be produced, resulting in what we refer to as “pop up-immunity”: a rapidly-established window of immune protection against the virus.

Antibody production lasts a number of weeks or even months and is effective regardless of what the recipient’s immune system is like or whether they are infected or not. Creating pop-up immunity with Gene MAbs™, which are both cost-effective and scalable for large population protection, introduces a way to quickly mount a protective immune barrier in treated people and reduce the infectivity of the virus in larger populations.