A single HBsAg DNA vaccination in combination with electroporation elicits long-term antibody responses in sheep

Babiuk, Shawn; Tsang, Cemaine; Hurk, Sylvia van Drunen Littel‐van den; Babiuk, Lorne A.; Griebel, Philip

doi:10.1016/j.bioelechem.2006.10.003

Cited by 33 publications

(22 citation statements)

References 28 publications

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“…Woodchuck PBMCs were isolated from whole blood and stimulated in the presence of [2][3] H]adenine (Amersham Pharmacia Biotech, Inc., Arlington Heights, IL) as described previously (34). Counts per minute (cpm) of triplicate PBMC cultures were averaged and expressed as a stimulation index (SI) by dividing the average sample cpm in the presence of the stimulator by the average cpm obtained in the absence of stimulator (six replicates).…”

Section: Methodsmentioning

confidence: 99%

“…Electroporation (EP) enhances the uptake of DNA vaccines by cells, resulting in significantly increased potency and immunogenicity of pDNA vaccines in several animal models, without adverse responses (1,2,4,19,25,26,35,38,44,48,49). For example, the EP immunization of mice, pigs, sheep, and rhesus macaques with pDNA vectors expressing HBsAg and/or HBV core protein (HBcAg) demonstrated dose-dependent humoral and cellular immune responses to both antigens (including multispecific CTL as an indicator of Th1 bias) that were superior to those induced by standard hypodermic needle injection (HI) of the same vectors (1,2,19,24,25,48,49). Although the exact mechanisms by which pDNA vaccines elicit such effects are not fully elaborated, the capacity to induce strong Th1 cellular responses to HBV antigens is considered essential for activating antiviral immunity that could lead to the clearance of HBV infection in chronically infected humans (3,5).…”

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confidence: 99%

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Electroporation Enhances Immunogenicity of a DNA Vaccine Expressing Woodchuck Hepatitis Virus Surface Antigen in Woodchucks

Liu

Ascenzi

Bellezza

et al. 2011

J Virol

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The development of therapeutic vaccines for chronic hepatitis B virus (HBV) infection has been hampered by host immune tolerance and the generally low magnitude and inconsistent immune responses to conventional vaccines and proposed new delivery methods. Electroporation (EP) for plasmid DNA (pDNA) vaccine delivery has demonstrated the enhanced immunogenicity of HBV antigens in various animal models. In the present study, the efficiency of the EP-based delivery of pDNA expressing various reporter genes first was evaluated in normal woodchucks, and then the immunogenicity of an analog woodchuck hepatitis virus (WHV) surface antigen (WHsAg) pDNA vaccine was studied in this model. The expression of reporter genes was greatly increased when the cellular uptake of pDNA was facilitated by EP. The EP of WHsAg-pDNA resulted in enhanced, dose-dependent antibody and T-cell responses to WHsAg compared to those of the conventional hypodermic needle injection of WHsAg-pDNA. Although subunit WHsAg protein vaccine elicited higher antibody titers than the DNA vaccine delivered with EP, T-cell response rates were comparable. However, in WHsAg-stimulated mononuclear cell cultures, the mRNA expression of CD4 and CD8 leukocyte surface markers and Th1 cytokines was more frequent and was skewed following DNA vaccination compared to that of protein immunization. Thus, the EP-based vaccination of normal woodchucks with pDNA-WHsAg induced a skew in the Th1/Th2 balance toward Th1 immune responses, which may be considered more appropriate for approaches involving therapeutic vaccines to treat chronic HBV infection.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Electroporation Enhances Immunogenicity of a DNA Vaccine Expressing Woodchuck Hepatitis Virus Surface Antigen in Woodchucks

Liu

Ascenzi

Bellezza

et al. 2011

J Virol

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“…EP, which can enhance in vivo naked plasmid DNA delivery in various tissues, has been widely used in DNA vaccination in many animal tests and clinical trials. 16,31,32 The enhancement of DNA vaccine potency by EP is consistent with the efficient intracellular transfer of the plasmid DNA and the induction of acute inflammation and cell infiltration of EP-mediated DNA delivery. [33][34][35][36] In this study, we used sf-DNA as helper molecules in EP-mediated gWIZ-GFP and pSEAP i.m.…”

Section: Discussionmentioning

confidence: 63%

Short noncoding DNA fragments improve the immune potency of electroporation-mediated HBV DNA vaccination

et al. 2014

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Electroporation (EP)-mediated DNA immunization can elicit effective immune responses in a variety of animals, and is widely used in research studies and clinical trials. However, high-pulse voltage, high DNA dose and multiple immunizations are still required to achieve considerable immune responses. To further improve the efficiency of EP-mediated DNA immunization, many parameters have been tried and optimized in recent years. In our early research, we found that the short noncoding DNA fragments (sf-DNA) can significantly enhance EP-mediated transgene expression of reporter genes. In this study, we tested the effect of sf-DNA on the immune potency of EP-mediated hepatitis B virus (HBV) DNA vaccination in a mouse model. The results show that the use of sf-DNA in EP-mediated HBV DNA vaccination leads to an enhanced expression of the HBV surface antigen, resulting in higher cellular and humoral responses. Furthermore, the immune responses in the sf-DNA-mediated 120 V cm(-1) EP immunization group were higher than that of the 200 V cm(-1) EP without sf-DNA groups. These data suggest that the sf-DNA can be used as an effective helper molecule to improve the immune response of EP-mediated HBV DNA vaccination, which may make the EP-mediated DNA vaccination more effective and suitable for animal and clinical application.

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“…This trial showed that two doses spaced 6 or 12 weeks apart are sufficient, while the third dose is not beneficial. Since electroporation enhances not only the magnitude but also the duration of immunity by DNA immunization (14,15), we then performed a second trial in which the interval between vaccination and challenge was extended. This demonstrated that two doses of the E2 DNA vaccine can induce protective immunity in newborn calves against BVDV challenge for several months.…”

Section: B Ovine Viral Diarrhea Virus (Bvdv) Is a Pestivirus In The Fmentioning

confidence: 99%

Two Doses of Bovine Viral Diarrhea Virus DNA Vaccine Delivered by Electroporation Induce Long-Term Protective Immune Responses

Hurk

Lawman

Snider

et al. 2013

Clin Vaccine Immunol

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Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

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A single HBsAg DNA vaccination in combination with electroporation elicits long-term antibody responses in sheep

Cited by 33 publications

References 28 publications

Electroporation Enhances Immunogenicity of a DNA Vaccine Expressing Woodchuck Hepatitis Virus Surface Antigen in Woodchucks

Electroporation Enhances Immunogenicity of a DNA Vaccine Expressing Woodchuck Hepatitis Virus Surface Antigen in Woodchucks

Short noncoding DNA fragments improve the immune potency of electroporation-mediated HBV DNA vaccination

Two Doses of Bovine Viral Diarrhea Virus DNA Vaccine Delivered by Electroporation Induce Long-Term Protective Immune Responses

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