Anti-Zika Virus DNA Vaccine
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Anti-Zika Virus DNA Vaccine

Team Representative:
Pablo Tebas, MD
Professor of Medicine
Perelman School of Medicine at the University of Pennsylvania 
E-mail: pablo.tebas@uphs.upenn.edu

Media Contact:
Holly Auer
E-mail: holly.auer@uphs.upenn.edu
Phone: 215-349-5659

Summary of findings in layman's terms:

In this phase 1 study (ZIKA-001), a total of 40 participants (20 in each of two groups) received GLS-5700, a new DNA vaccine against two proteins of the Zika virus in a 1 mg or 2 mg dose. The vaccine was administered in 0.1 ml intradermal injections administered by CELLECTRA® 3P skin vaccine device that increases the expression of the injected DNA. 

The GLS-5700 Zika vaccine induced binding antibodies in 100% of the participants after a three-dose vaccination regimen and in 95% after two doses of vaccine. In addition, neutralizing antibodies were observed in more than 95% of the serum samples that were assayed on neuronal-cell targets. 

Serum samples from vaccinated subjects when subsequently transferred to mice were found to be protective from death and illness in more than 90% of animals after they were challenged with a lethal dose of the Zika virus.

This is the first trial of a Zika vaccine in humans.

Specific biological innovation of study:

Currently, there are no licensed vaccines against ZIKV infection. This clinical trial provides initial data on the safety and immunogenicity of the GLS-5700 ZIKV vaccine, which induced binding antibodies in 100% of the participants after a three-dose vaccination regimen and in 95% after two doses of vaccine.

Immune serum that was obtained from vaccinated study participants both prevented ZIKV infection in cellular models in vitro and prevented death in an in vivo mouse model.

Synthetic DNA vaccines are appropriate for emerging infectious diseases because they allow for the rapid design of novel antigens. Vaccines can be rapidly designed with the use of a common platform expressing relevant antigens from an emergent pathogen.

Our study further advances the approaches for enhancing electroporation by focusing on intradermal injection of a decreased delivery volume with a decreased energy output during electroporation. GLS-5700 was associated with rates of local and systemic side effects that were similar to those of other DNA vaccines delivered by means of electroporation.

Our trial shows the initial safety and immunogenicity of a DNA vaccine encoding consensus ZIKV premembrane and envelope antigens delivered by means of electroporation. 

Potential impact on human care and/or how the findings contributed to an improved understanding:

Currently, there are no licensed vaccines against ZIKV infection. This clinical trial provides initial data on the safety and immunogenicity of the GLS-5700 ZIKV vaccine, which induced binding antibodies in 100% of the participants after a three-dose vaccination regimen and in 95% after two doses of vaccine.
 
After outbreaks in Yap Island and French Polynesia, ZIKV infection was identified in Brazil in 2015 and has spread rapidly throughout the Americas. ZIKV infection is typically self-limiting and manifests as fever, rash, conjunctivitis, arthralgias, and, uncommonly, neurologic syndromes such as the Guillain-Barré syndrome. ZIKV infection during pregnancy has been associated with severe congenital birth defects. ZIKV can persist in bodily fluids, particularly semen, for up to 6 months after infection.
 
Our trial was the first Zika vaccine trial in humans that demonstrated the safety and immunogenicity of a DNA vaccine encoding envelope antigens delivered by means of electroporation. 
 
Our passive transfer of antibodies demonstrated the effectiveness of the vaccines in potentially preventing this devastating infection.
 
Further studies will be needed to evaluate the efficacy of the vaccine and its long-term safety. 

Journal citation: 

Tebas P, Roberts CC, Muthumani K, Reuschel EL,Kudchodkar SB, Zaidi FI, White S, Khan AS, RacineT, Choi H, Boyer J, Park YK, Trottier S, Remigio C, Krieger D, Spruill SE, Bagarazzi M, Kobinger GP, Weiner DB, Maslow JN.

Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine
- Preliminary Report.

N Engl J Med. 2017 Oct 4.
doi: 10.1056/NEJMoa1708120. [Epub ahead of print].
https://www.ncbi.nlm.nih.gov/pubmed/2897685