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Vaccine2016; 34(31); 3607-3612; doi: 10.1016/j.vaccine.2016.04.077

A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation.

Abstract: Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983.
Published by Elsevier Ltd.
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Publication Date: 2016-05-17 PubMed ID: 27206386DOI: 10.1016/j.vaccine.2016.04.077Google Scholar: Lookup
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  • Clinical Trial
  • Phase I
  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research describes a Phase 1 clinical trial that tests a DNA vaccine for the Venezuelan equine encephalitis virus, which is an infectious disease spread by mosquitoes. Injecting this vaccine through electroporation, either intramuscularly or intradermally, appears to be safe, acceptable, and capable of triggering a protective immune response.

Introduction and Background

  • The research attempts to devise a cure for Venezuelan equine encephalitis virus (VEEV), which is a mosquito-borne virus harmful to horses and can also infect humans. There are no existing licensed vaccines against this virus.
  • The researchers have developed a candidate DNA vaccine designated pWRG/VEE. This vaccine contains the E3-E2-6K-E1 genes from VEEV.

Methodology

  • The study involves a Phase 1 clinical trial with the primary objective of assessing the safety, tolerability, reactogenicity (ability to produce common, short-term side effects), and immunogenicity (ability to provoke an immune response) of the pWRG/VEE vaccine when administered by intramuscular (IM) or intradermal (ID) electroporation (EP).
  • The vaccination was carried out using the Ichor Medical Systems TriGrid™ Delivery System.
  • The researchers carefully divided subjects into different dose groups for IM and ID delivery, as well as saline placebo controls. They monitored these subjects for a period of 360 days following administration of the vaccine.

Key Findings

  • During the course of the trial, no serious side effects were reported that could be linked directly to the vaccine or the delivery device.
  • A survey among the subjects revealed that both IM and ID electroporation procedures were assessed as generally acceptable for administering the preventive vaccine. However, the tolerability of the ID-EP method was rated higher than the IM-EP method.
  • All subjects in the high and low dose IM-EP groups developed detectable antibodies that neutralize the VEEV after two or three doses of pWRG/VEE respectively. Moreover, VEEV-neutralizing antibody responses were detected in a significant proportion of the subjects in the high dose and low dose ID-EP groups as well after three injections of the vaccine.
  • There was a notable correlation between the DNA dose of the vaccine and the magnitude of the resulting VEEV-neutralizing antibody responses for both the IM- and ID-EP delivery methods.

Conclusion

  • Given the promising results, the researchers concluded that the pWRG/VEE vaccine, delivered either intramuscularly or intradermally via electroporation, proved to be safe, tolerable, and successfully induced an immune response at the evaluated dose levels.
  • The study has been registered at Clinicaltrials.gov with the registry number NCT01984983.

Cite This Article

APA
Hannaman D, Dupuy LC, Ellefsen B, Schmaljohn CS. (2016). A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation. Vaccine, 34(31), 3607-3612. https://doi.org/10.1016/j.vaccine.2016.04.077

Publication

Vaccine
ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 34
Issue: 31
Pages: 3607-3612
PII: S0264-410X(16)30242-0

Researcher Affiliations

Hannaman, Drew
  • Ichor Medical Systems, Inc., San Diego, CA, USA.
Dupuy, Lesley C
  • United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
Ellefsen, Barry
  • Ichor Medical Systems, Inc., San Diego, CA, USA.
Schmaljohn, Connie S
  • United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. Electronic address: connie.s.schmaljohn.civ@mail.mil.

MeSH Terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Double-Blind Method
  • Electroporation
  • Encephalitis Virus, Venezuelan Equine
  • Encephalomyelitis, Venezuelan Equine / prevention & control
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Injections, Intradermal
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / therapeutic use
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / therapeutic use
  • Young Adult

Citations

This article has been cited 40 times.
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