The coronavirus disease (COVID-19) is far from over as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to ravage across the globe. With the vast spread of the virus, many countries who reported flattening the curve over the past months have reported clusters of new cases and second waves of the outbreak.

One way scientists believe will help contain the spread of the virus and potentially ending the pandemic is by developing an effective and safe vaccine. The World Health Organization (WHO) reports that there are over 200 candidate vaccines against SARS-CoV-2, while 44 are in clinical evaluation.

Several vaccines being developed and tested for COVID-19 are DNA-based, which uses a novel technique called DNA immunization to stimulate humoral and cellular immune responses to protein antigens efficiently.

Now, a team of researchers at Osaka University in Japan confirmed the neutralizing action of DNA vaccine-induced antibodies through two methods – a binding assay of Receptor Binding Domain (RBD) recombinant protein with angiotensin-converting-enzyme 2 (ACE2) and pseudovirus assay.

Study: Preclinical study of DNA vaccines targeting SARS-CoV-2. Image Credit: phichak / Shutterstock

What are DNA-based vaccines?

Vaccination works by triggering the immune system with an infectious agent, or components of an infectious agent, modified in such a way that it causes no harm to the human body. When these agents are introduced in the body, it induces the immune system to neutralize them before they cause disease.

Over the past years, many types of vaccines have been developed, including the novel DNA-based vaccine. It involves using engineered DNA to stimulate an immunologic response in the host against pathogens, such as parasites, bacteria, and viruses.

A DNA vaccine uses a DNA plasmid that encodes for a protein coming from the pathogen. Plasmid DNA (pDNA) is affordable, stable, and sage, making it an excellent gene delivery option. Further, DNA vaccines have many advantages, including being quickly produced by PCR or synthetic methods, and can be produced on large scales. They are safer than other approaches, such as inactivated virus vaccines, and they are more thermostable than other vaccines.

The study

In the study, which appeared in the pre-print server bioRxiv*, the research team developed a DNA-based vaccine that targets the SARS-CoV-2 spike glycoprotein, which the virus uses to attach to the cell's ACE2 receptor. The spike protein and ACE2 receptor site act as a lock-and-key for viral entry into healthy cells. Using the ACE2 as a cellular gateway, the virus can enter the cell to cause infection and proliferation in the body.

In the study, the team measures antibody production by an antigen-specific enzyme-linked immunosorbent assay (ELISA) to represent the humoral response and antigen-dependent T cell activation by an enzyme-linked immunosorbent spot (ELISpot) assay to evaluate for cellular responses. Also, they assessed the functional activity of immune responses in vitro in neutralization assays using the pseudovirion virus.

The DNA vaccine, pVAX1, was obtained from Invitrogen in the United States. The team also obtained the virus RNA of SARS-CoV-2 from the National Institute of Infectious Disease. Also, they developed a highly optimized DNA sequence encoding the SARS-CoV-2 spike glycoprotein using an in-silico gene optimization algorithm to boost expression and immunogenicity. This was injected and inserted into the pVAX1 plasmid. They also obtained the adjuvant used in the study, alum phosphate, from InVivogen in the U.S.

The researchers described the pre-clinical effectiveness and safety studies of DNA vaccines for SARS-CoV-2, the virus that causes COVID-19. They confirmed the expression and immunogenicity of the DNA vaccine in in-vitro and in-vivo studies and evaluated the cellular, humoral, and functional immune responses.

The DNA vaccine is now in phase ½ of a clinical trial in Japan. The trial's preliminary data demonstrated no adverse effects, similar to previous data of safety profile using DNA vaccines against other infectious diseases.

In a nutshell, the DNA vaccine trial's initial results described the immunogenicity of DNA vaccine targeting S protein for SARS-CoV-2 might serve as evidence to process for clinical trials. The researchers believe that developing DNA vaccines against SARS-CoV-2 may help stem the current COVID-19 pandemic, which has infected at least 41 million people and has claimed the lives of more than 1.13 million people.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


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