Immunogenicity and efficacy of a plasmid DNA rabies vaccine incorporating Myd88 as a genetic adjuvant

Ullas, Padinjaremattathil Thankappan; Desai, Anita; Madhusudana, Shampur Narayan

doi:10.7774/cevr.2014.3.2.202

Cited by 7 publications

(3 citation statements)

References 37 publications

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“…An alternative to using TLR ligands is the expression of proteins which mediate signaling directly downstream of activated TLRs. This was tested by incorporating two genes, MyD88 and TRIF, into DNA-vaccine plasmids against influenza or rabies [ 72 , 73 ]. Both genetic adjuvants were able to enhance the resulting immune responses.…”

Section: Genetic Adjuvantsmentioning

confidence: 99%

Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

Grünwald

Ulbert

2015

Clin Exp Vaccine Res

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Advantages of DNA vaccination against infectious diseases over more classical immunization methods include the possibilities for rapid manufacture, fast adaptation to newly emerging pathogens and high stability at ambient temperatures. In addition, upon DNA immunization the antigen is produced by the cells of the vaccinated individual, which leads to activation of both cellular and humoral immune responses due to antigen presentation via MHC I and MHC II molecules. However, so far DNA vaccines have shown most efficient immunogenicity mainly in small rodent models, whereas in larger animals including humans there is still the need to improve effectiveness. This is mostly due to inefficient delivery of the DNA plasmid into cells and nuclei. Here, we discuss technologies used to overcome this problem, including physical means such as in vivo electroporation and co-administration of adjuvants. Several of these methods have already entered clinical testing in humans.

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Section: Genetic Adjuvantsmentioning

confidence: 99%

Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

Grünwald

Ulbert

2015

Clin Exp Vaccine Res

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“… 14 showed that a DAI-expressing plasmid can be efficiently used as a genetic cancer vaccine inducing memory and effector tumor-specific T-cells. Similarly, myeloid differentiation factor 88 (MyD88), a ubiquitous Toll-like receptor adaptor molecule, has been used as a genetic adjuvant to harness intrinsic immune-stimulating properties of a DNA vaccine 15 and a MyD88-encoding adenovirus was shown to potentiate local and systemic antitumor immunity. 16 …”

Section: Introductionmentioning

confidence: 99%

Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity

Hirvinen

Capasso

Guse

et al. 2016

Molecular Therapy - Oncolytics

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In oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. Vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. However, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. To overcome this problem, we developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI) to boost the innate immune system and to activate adaptive immune cells in the tumor. We showed that infection with DAI-expressing VV increases expression of several genes related to important immunological pathways. Treatment with DAI-armed VV resulted in significant reduction in the size of syngeneic melanoma tumors in mice. When the mice were rechallenged with the same tumor, DAI-VV-treated mice completely rejected growth of the new tumor, which indicates immunity established against the tumor. We also showed enhanced control of growth of human melanoma tumors and elevated levels of human T-cells in DAI-VV-treated mice humanized with human peripheral blood mononuclear cells. We conclude that expression of DAI by an oncolytic VV is a promising way to amplify the vaccine potency of an oncolytic vaccinia virus to trigger the innate—and eventually the long-lasting adaptive immunity against cancer.

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“…The principle of DNA vaccines has been confirmed for rabies virus in small animal models in which they demonstrate immunogenicity [18], but this has not translated into effective vaccines in larger animals, and they are poorly immunogenic in humans [19]. Further, there is concern, so far with no supporting evidence, that exogenous DNA could be incorporated into the host genome.…”

Section: Dna Vaccinesmentioning

confidence: 99%

Advances in RNA Vaccines for Preventive Indications: A Case Study of a Vaccine against Rabies

2019

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: There is a global need for effective and affordable rabies vaccines, which is unmet by current vaccines due to limitations in their production capacities, required administration schedules, storage requirements, and cost. Many different experimental approaches previously used for bacterial and viral vaccines have been applied to rabies, but with variable success. One of the most promising new concepts is the use of messenger RNA (mRNA) in encoding the main rabies virus antigen, the envelope glycoprotein (RABV-G). CureVac has applied their proprietary technology platform for the production of mRNA to this problem, resulting in the rabies vaccine candidate CV7201. Following preclinical studies in mice and pigs showing that CV7201 could induce neutralizing immune responses that protected against rabies virus, different dosages and routes of administration of CV7201 were tested in a phase 1 human study. This clinical study proved that mRNA vaccination was safe and had an acceptable reactogenicity profile, but immune responses depended on the mode of administration, and they did not unequivocally support CV7201 for further development as a prophylactic vaccine with this particular formulation. Further, preclinical studies using RABV-G mRNA encapsulated in lipid nanoparticles (LNPs) showed an improved response in both mice and nonhuman primates, and these encouraging results are currently being followed up in clinical studies in humans. This review summarizes the recent advances in mRNA vaccines against rabies.

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Immunogenicity and efficacy of a plasmid DNA rabies vaccine incorporating Myd88 as a genetic adjuvant

Cited by 7 publications

References 37 publications

Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity

Advances in RNA Vaccines for Preventive Indications: A Case Study of a Vaccine against Rabies

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