The Zika DNA Vaccine: Optimizing Delivery Mode to Optimize Protection
Update 09.11.2022
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 Leea, Heeji Limb, Jung-Ah Leec, Su Hwan Kima,
Yun-Ho Hwangc, Hyun Ju Inb, Mi Young Kimb,
Gyung Tae Chungb
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.