Nanogram quantities of plasmid DNA encoding the rabies virus glycoprotein protect mice against lethal rabies virus infection

Ray, Nancy B.; Ewalt, Larry C.; Lodmell, Donald L.

doi:10.1016/s0264-410x(96)00281-2

Cited by 63 publications

(28 citation statements)

References 6 publications

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“…However, microorganisms contain surface-molecules such as LPS and a variety of soluble factors that function as adjuvants, alerting the immune system to 'danger' by inducing inflammation. The potency of genetic vaccines may be significantly enhanced by mimicking these signals with synthetic adjuvants such as QS21 [26] or monophosphoryl lipid A (MPL) [30,31]. However, DNA plasmids without adjuvant are able to induce remarkably strong immune responses to the encoded antigen.…”

Section: A Variety Of Factors Determine the Success Of Genetic Vaccinmentioning

confidence: 99%

DNA and RNA-based vaccines: principles, progress and prospects

Leitner

Han

Restifo

1999

Vaccine

339

229

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DNA vaccines were introduced less than a decade ago but have already been applied to a wide range of infectious and malignant diseases. Here we review the current understanding of the mechanisms underlying the activities of these new vaccines. We focus on recent strategies designed to enhance their function including the use of immunostimulatory (CpG) sequences, dendritic cells (DC), costimulatory molecules and cytokine-and chemokine-adjuvants. Although genetic vaccines have been significantly improved, they may not be sufficiently immunogenic for the therapeutic vaccination of patients with infectious diseases or cancer in clinical trials. One promising approach aimed at dramatically increasing the immunogenicity of genetic vaccines involves making them 'selfreplicating'. This can be accomplished by using a gene encoding RNA replicase, a polyprotein derived from alphaviruses, such as Sindbis virus. Replicase-containing RNA vectors are significantly more immunogenic than conventional plasmids, immunizing mice at doses as low as 0.1 μg of nucleic acid injected once intramuscularly. Cells transfected with 'self-replicating' vectors briefly produce large amounts of antigen before undergoing apoptotic death. This death is a likely result of requisite double-stranded (ds) RNA intermediates, which also have been shown to super-activate DC. Thus, the enhanced immunogenicity of 'self-replicating' genetic vaccines may be a result of the production of pro-inflammatory dsRNA, which mimics an RNA-virus infection of host cells.

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Section: A Variety Of Factors Determine the Success Of Genetic Vaccinmentioning

confidence: 99%

DNA and RNA-based vaccines: principles, progress and prospects

Leitner

Han

Restifo

1999

Vaccine

339

229

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show abstract

“…In fact, the VSV G protein has been shown to be an excellent T-independent antigen [43], as occurs with other viral proteins [44]. Interestingly, one of the most effective DNA vaccines tested in mice has been a glycoprotein-encoding DNA vaccine against rabies, another rhabdovirus [45]. Thus, it might be relevant to evaluate whether the responses elicited by all rhabdoviral DNA vaccines have important T-independent components that render them especially effective.…”

Section: Discussionmentioning

confidence: 99%

DNA vaccination against a fish rhabdovirus promotes an early chemokine-related recruitment of B cells to the muscle

Castro¹,

Martinez-Alonso²,

Fischer³

et al. 2014

Vaccine

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a b s t r a c tIn fish, intramuscular (i.m) injection of plasmid DNA encoding viral proteins has proved a highly effective vaccination strategy against some viral pathogens. The efficacy of DNA vaccination in teleost fish is based on the high level of viral antigen expression in muscle cells inducing a strong and long-lasting protection. However, the mechanisms through which this protection is established and effectuated in fish are still not fully understood. Moreover, similarities to mammalian models cannot be established since DNA vaccination in mammals usually induces much weaker responses. In this work, we have focused on the characterization of the immune cells that infiltrate the muscle at the site of DNA injection in vaccinated fish and the chemokines and chemokine receptors that may be involved in their infiltration. We have demonstrated through diverse techniques that B lymphocytes, both IgM + and IgT + cells, represented a major infiltrating cell type in fish vaccinated with a viral haemorrhagic septicaemia virus (VHSV) glycoprotein-encoding DNA vaccine, whereas in control fish injected with an oil adjuvant mainly granulocyte/monocyte-type cells were attracted. Among twelve chemokine genes studied, only CXCL11 L1, CK5B and CK6 mRNA levels were up-regulated in DNA vaccinated fish compared to fish injected with the corresponding vector backbone. Furthermore, the transcription of CXCR3B, a possible receptor for CXCL11 L1 was also significantly up-regulated in vaccinated fish. Finally, experiments performed with recombinant trout CK5B and CK6 and chemokine expression plasmids revealed that these chemokines have chemotactic capacities which might explain the recruitment of B cells to the site of DNA injection. Altogether, our results reveal that there is an early chemokine-related B cell recruitment triggered by i.m. DNA vaccination against VHSV which might play an important role in the initial phase of the immune response.

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“…For delivery of DNA vaccines, a variety of methods including intradermal, intramuscular (i.m. ), mucosal, biojector injections and EP have been reported (Fynan et al, 1993;Pertmer et al, 1995;Kuklin et al, 1997;Ray et al, 1997;Chen et al, 1998;Luckay et al, 2007;Rosati et al, 2009). To date, the majority of DNA vaccine studies have utilized skin or muscle as an immunization target.…”

Section: Mechanism Of Dna Vaccinesmentioning

confidence: 99%

DNA Vaccines against Infectious Diseases and Cancer

Han¹,

Weiner²,

Sin³

2010

Biomolecules and Therapeutics

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-Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.

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Nanogram quantities of plasmid DNA encoding the rabies virus glycoprotein protect mice against lethal rabies virus infection

Cited by 63 publications

References 6 publications

DNA and RNA-based vaccines: principles, progress and prospects

DNA and RNA-based vaccines: principles, progress and prospects

DNA vaccination against a fish rhabdovirus promotes an early chemokine-related recruitment of B cells to the muscle

DNA Vaccines against Infectious Diseases and Cancer

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