DNA-based Zika Vaccine Demonstrates Potential in Animal Models
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By Gerald M. Slutzky, PhD Posted on 22 Nov 2016 |
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Image: A digitally colorized transmission electron micrograph (TEM) of Zika virus. Virus particles, here colored red, are 40 nanometers in diameter, with an outer envelope, and an inner dense core (Photo courtesy of the CDC).
A DNA-based vaccine has shown promise in protecting animal models against infection and brain damage caused by the Zika virus.
Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre’ syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection.
A recent paper described clinical studies carried out in mice and non-human primates that were vaccinated with a DNA-based vaccine developed by collaboration between Inovio Pharmaceuticals (Plymouth Meeting, PA, USA), The Wistar Institute (Philadelphia, PA, USA), and GeneOne Life Science Inc. (Seoul, Korea).
The DNA vaccine targeted the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunized with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery.
Results reported in the November 10, 2016, online edition of the journal npj Vaccines revealed that vaccinated animals generated antigen-specific cellular and humoral immunity and neutralization activity. In mice lacking receptors for interferon (IFN)-alpha/beta (designated IFNAR−/−) immunization with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR−/− mice against subsequent viral challenge.
Results obtained in this study in non-human primates and in a pathogenic mouse model supported the importance of immune responses targeting prME in ZIKV infection and suggested that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.
"Our results support the critical importance of immune responses for both preventing infection as well as ameliorating disease caused by the Zika virus," said senior author Dr. David B. Weiner, director of the vaccine center at The Wistar Institute. "As the threat of Zika continues, these results provide insight into a new aspect of the possibly protective ability of such a vaccine as a preventative approach for Zika infection."
Dr. J. Joseph Kim, president and CEO of Inovio Pharmaceuticals, Inc., said, "Working with Wistar, we have clearly demonstrated the power and the speed of our product development platform when we and our collaborators moved our Zika vaccine from the bench to human studies in less than six months, taking advantage of our platform to help in this outbreak situation."
Related Links:
Inovio Pharmaceuticals
The Wistar Institute
GeneOne Life Science
Significant concerns have been raised owing to the rapid global spread of infection and disease caused by the mosquito-borne Zika virus (ZIKV). Recent studies suggest that ZIKV can also be transmitted sexually, further increasing the exposure risk for this virus. Associated with this spread is a dramatic increase in cases of microcephaly and additional congenital abnormalities in infants of ZIKV-infected mothers, as well as a rise in the occurrence of Guillain Barre’ syndrome in infected adults. Importantly, there are no licensed therapies or vaccines against ZIKV infection.
A recent paper described clinical studies carried out in mice and non-human primates that were vaccinated with a DNA-based vaccine developed by collaboration between Inovio Pharmaceuticals (Plymouth Meeting, PA, USA), The Wistar Institute (Philadelphia, PA, USA), and GeneOne Life Science Inc. (Seoul, Korea).
The DNA vaccine targeted the pre-membrane+envelope proteins (prME) of ZIKV. Following initial in vitro development and evaluation studies of the plasmid construct, mice and non-human primates were immunized with this prME DNA-based immunogen through electroporation-mediated enhanced DNA delivery.
Results reported in the November 10, 2016, online edition of the journal npj Vaccines revealed that vaccinated animals generated antigen-specific cellular and humoral immunity and neutralization activity. In mice lacking receptors for interferon (IFN)-alpha/beta (designated IFNAR−/−) immunization with this DNA vaccine induced, following in vivo viral challenge, 100% protection against infection-associated weight loss or death in addition to preventing viral pathology in brain tissue. In addition, passive transfer of non-human primate anti-ZIKV immune serum protected IFNAR−/− mice against subsequent viral challenge.
Results obtained in this study in non-human primates and in a pathogenic mouse model supported the importance of immune responses targeting prME in ZIKV infection and suggested that additional research on this vaccine approach may have relevance for ZIKV control and disease prevention in humans.
"Our results support the critical importance of immune responses for both preventing infection as well as ameliorating disease caused by the Zika virus," said senior author Dr. David B. Weiner, director of the vaccine center at The Wistar Institute. "As the threat of Zika continues, these results provide insight into a new aspect of the possibly protective ability of such a vaccine as a preventative approach for Zika infection."
Dr. J. Joseph Kim, president and CEO of Inovio Pharmaceuticals, Inc., said, "Working with Wistar, we have clearly demonstrated the power and the speed of our product development platform when we and our collaborators moved our Zika vaccine from the bench to human studies in less than six months, taking advantage of our platform to help in this outbreak situation."
Related Links:
Inovio Pharmaceuticals
The Wistar Institute
GeneOne Life Science
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