National Institute of Health

Scientists reveal that the effectiveness of DNA vaccines can be enhanced by using a specific delivery route

Alongside the now much popularized mRNA vaccine, DNA vaccines are also being developed for certain diseases. As part of that effort, researchers from the Republic of Korea have created several candidates for the Zika virus. In their latest study, they investigated the optimal delivery route for one of their candidates and found that immune response and protection are greatly superior when the vaccine is delivered through an unconventional but established technique called electroporation, opening doors to new vaccine exploration pathways.

Optimizing the DNA vaccine for the Zika virus

What is the optimal delivery mode and dosage for a DNA vaccine candidate for the Zika vaccine? Scientists from the Republic of Korea find out.

Image credits: Shutterstock

The Zika virus, first reported in Brazil in 2015, caused only mild symptoms, like fever, muscle numbness, and headache in adults. But in fetuses, it caused serious neurological problems like the Guillain-Barre syndrome (a medical condition in which body’s immune system attacks the nerves) or congenital microcephaly (improper growth of the brain). And while the incidence of Zika infections appears to be declining globally, this danger to pregnant women coupled with the fact that it has also been found to enhance dengue severity, make it quite dangerous. Yet, no vaccine or therapy for it exists.

But this does not mean that global effort has not been afoot to develop vaccines and therapies in preparation for a plausible Zika epidemic/pandemic situation. As part of this effort, scientists from the Korea Disease Control and Prevention Agency, led by Dr. Gyung Tae Chung, have developed six DNA vaccine candidates. In their latest study, they arrive at the optimal dose and vaccine delivery route. Their findings are published in Virology. Their work was supported by grants from the Korea Disease Control and Prevention Agency (4800-4845-300 and 4800-4859-300); the intramural research number is 2019-NI096-00.

DNA vaccines are created from the genes of a virus. When our immune system encounters a small identificatory piece of the viral DNA, and immune response and memory is created against the target virus, in this case, Zika. DNA vaccines come with benefits of fast development, low-cost manufacturing, and stability. They are also reported to induce a robust immune response. This makes them a convenient alternative to conventional vaccine types for rapid commercial vaccine development and deployment in all infectious diseases.

The catch, however, is that their efficacy depends largely on their mode of delivery. Dr. Jung-Ah Lee, who worked as a staff scientist and designed the majority of the experiment, explains: “Our immune system responds differently to different routes of vaccine administration. Hence, there is a need to optimize the vaccine delivery to achieve maximum protection.”  The regular arm shot, which is an intramuscular (IM) injection, may not necessarily be the most effective.

Thus, Dr. Chung’s team investigated three vaccine delivery routes for one of their DNA vaccine candidates, ED III x 3: IM, jet injection (JET; a relatively new, needle free, and painless method of vaccine delivery), and electroporation (EP; using short electric pulses to aid vaccine entry into cells).

Via experiments with mice and then various immunoassay tests, they found that the vaccine induced the highest antibody production when delivered through the EP route. Further, mice immunized with the vaccine and then exposed to the Zika Brazil strain showed a survival rate of 40% in the cases of IM and JET deliveries, and 60% in the case of delivery through EP. This meant that EP ensured greater immune response and protection than the other two delivery modes.

The scientists then injected mice with 50 µg, 100 µg, and 200 µg of the vaccine using the EP route to find the optimal dose. Similar levels of antibodies appeared for all three doses; but T cell (important components of the immune system involved in creating memory of a pathogen and later killing it) response was significantly higher for the 50 µg dose.

Summarizing their findings, Dr. Lee says, “Our work shows that a 50 µg dose of the ED III x 3 vaccine candidate, administered through the EP route, has maximum effectiveness against Zika. It also suggests that delivery through EP route enhances the potency of DNA vaccines.”

The scientists are hopeful that their study takes DNA vaccines for Zika viruses and other infections.

Reference

Authors                             Yun Ha Lee^a, Heeji Lim^b, Jung-Ah Lee^c, Su Hwan Kim^a, Yun-Ho Hwang^c, Hyun Ju In^b, Mi Young Kim^b, Gyung Tae Chung^b

Title of original paper        Optimization of Zika DNA vaccine by delivery systems

Journal                              Virology

DOI                                   10.1016/j.virol.2021.03.005

Affiliations                         ^aDivision of Vaccine Clinical Research, Center for Vaccine Research, National Institute of Infectious Diseases, 

                                           National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Chungcheongbuk-do, Republic of Korea

                                         ^bDivision of Vaccine Development Coordination, Center for Vaccine Research, National Institute of Infectious Diseases, 

                                           National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Chungcheongbuk-do, Republic of Korea

                                         ^cDivision of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Infectious Diseases,

                                           National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Chungcheongbuk-do, Republic of Korea

About National Institute of Health in Korea

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.

Website: http://www.nih.go.kr/eng/

About Dr. Gyung Tae Chung

As expert in infectious diseases, Gyung Tae Chung is currently a director at the Center for Infectious Disease Research, Korea National Institute of Health. He has been a scientist at KNIH for more than 25 years. He is an active member of The Korean Vaccine Society and The Korean Society of Clinical Microbiology. Previously, he conducted research as a visiting scientist at the Department of Medicine, Johns Hopkins University. After that, he was a postdoctoral fellow at the Department of Medicine, Thomas Jeffferson University, USA. To date, he has published more than 50 SCI papers.