Electroporation Advances in Large Animals

Reed, Scott D.; Li, Shulin

doi:10.2174/156652309788921062

Cited by 35 publications

(19 citation statements)

References 126 publications

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“…These findings suggest that this vaccine may represent a suitable alternative to the liveattenuated and formalin-inactivated VEEV vaccines currently used under IND status. Moreover, our results, along with those of others (5,41,49), recommend EP delivery as an effective method to elicit immunity in animals and humans, with a capacity large enough to accommodate multiple vaccines in a single administration.…”

Section: Discussionsupporting

confidence: 71%

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

Dupuy

Richards

Ellefsen

et al. 2011

Clin. Vaccine Immunol.

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We evaluated the immunogenicity and protective efficacy of a DNA vaccine expressing codon-optimized envelope glycoprotein genes of Venezuelan equine encephalitis virus (VEEV) when delivered by intramuscular electroporation. Mice vaccinated with the DNA vaccine developed robust VEEV-neutralizing antibody responses that were comparable to those observed after administration of the live-attenuated VEEV vaccine TC-83 and were completely protected from a lethal aerosol VEEV challenge. The DNA vaccine also elicited strong neutralizing antibody responses in rabbits that persisted at high levels for at least 6 months and could be boosted by a single additional electroporation administration of the DNA performed approximately 6 months after the initial vaccinations. Cynomolgus macaques that received the vaccine by intramuscular electroporation developed substantial neutralizing antibody responses and after an aerosol challenge had no detectable serum viremia and had reduced febrile reactions, lymphopenia, and clinical signs of disease compared to those of negative-control macaques. Taken together, our results demonstrate that this DNA vaccine provides a potent means of protecting against VEEV infections and represents an attractive candidate for further development.Venezuelan equine encephalitis virus (VEEV) is a nonsegmented, positive-sense RNA virus of the genus Alphavirus in the family Togaviridae (17). Naturally transmitted by mosquitoes through rodent hosts, VEEV is highly pathogenic for equines and humans and has sporadically caused widespread epidemics in North, Central, and South America (48). While most equine and human outbreaks have been caused by the epizootic IAB and IC subtypes of VEEV, isolated cases of disease caused in equines and humans by infection with the enzootic ID and IE subtypes have also been reported (10,32,50). Regardless of the variety, human infection with VEEV typically results in an acute, incapacitating, but self-limiting disease characterized by fever, headache, lymphopenia, myalgia, and malaise (3). Severe neurological disease, including fatal encephalitis, can also result from VEEV infection of humans, although the case fatality rate is estimated to be low (Յ1%) (45). However, numerous documented laboratory accidents and the results of animal studies have demonstrated that VEEV is also highly infectious in aerosols, and infection with aerosolized VEEV could potentially result in higher mortality than that observed with natural infection (15,18,26). In addition to producing incapacitating or lethal infections and being infectious in aerosols, VEEV is also easily grown to high titers in inexpensive and unsophisticated cell culture systems and is relatively stable (45). As a result, VEEV represents a significant potential biological defense threat and is classified as a category B priority biodefense agent by both the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases.There are no licensed human vaccines for VEEV. While live-attenuated...

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Section: Discussionsupporting

confidence: 71%

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

Dupuy

Richards

Ellefsen

et al. 2011

Clin. Vaccine Immunol.

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“…Several recent reviews describe the application of this technique to gene [1][2][3][4][5] and drug therapy. 4,[6][7][8][9] Over the past 15 years, EP has become a common technique for introducing large molecules into cells, both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs

Reed¹,

Fulmer²,

Buckholz³

et al. 2010

Cancer Gene Ther

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On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T 2b N 0 M 0 oral squamous cell carcinomas (SCCs) and one T 2 N 0 M 0 acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T 3b N 2b M 1 melanoma with pulmonary and lymph node metastases; one had cubital T 3 N 0 M 1 histiocytic sarcoma with spleen metastases; and one had soft palate T 3 N 0 M 0 fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T 3 N 0 M 0 fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

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“…However, it is not possible to directly compare the studies, since we used electroporation, whereas before other group used gene gun for immunization. Previously, it was suggested that different application methods of DNA vaccines have profound effects on immunogenicity [22].…”

Section: Discussionmentioning

confidence: 99%

“…In vivo electroporation has been shown to enhance the transfer of DNA vaccines in various animal species [22]. Furthermore, recent clinical studies suggest that electroporation of a DNA vaccine is able to induce a robust immune response in patients [23].…”

Section: Immunogenicity In Micementioning

confidence: 99%

Immunogenicity and Protective Efficiency in Mice of a Smallpox DNA Vaccine Candidate

Kim¹,

Chang²,

Hur³

et al. 2017

J Bioterror Biodef

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The adverse reactions of the current live smallpox vaccine, and potential use of smallpox as a bioterrorism weapon, have highlighted the need to develop a new effective vaccine for this infectious disease. In the present study, a DNA vaccine vector was produced, which was optimized for expression of the vaccinia virus L1 antigen in a mouse model. Plasmid-encoded IgM-tL1R, which contains a truncated L1R gene fused to an IgM signal sequence, was constructed and expressed under the regulation of an SV40 enhancer. The expressed recombinant tL1 proteins were successfully secreted into the culture media. The DNA vaccine was administered to mice by electroporation, and animals were subsequently challenged with the lethal dose of vaccinia virus. We observed that immunization with IgM-tL1R induced robust neutralizing antibody responses and provided complete protection against a vaccinia virus infection. Isotyping studies revealed a lower IgG1/IgG2a ratio following vaccination with IgM-tL1R, suggesting the stimulation of Th1 immune responses. Our results propose that an optimized DNA vaccine, IgM-tL1R, can be effective in eliciting an anti-vaccinia virus immune response and provide protection against lethal orthopoxvirus challenge.

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Electroporation Advances in Large Animals

Cited by 35 publications

References 126 publications

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates

Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs

Immunogenicity and Protective Efficiency in Mice of a Smallpox DNA Vaccine Candidate

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