Immune response induced by a linear DNA vector: Influence of dose, formulation and route of injection

Endmann, Anne; Baden, Michael M.; Weisermann, Elena; Kapp, Kerstin; Schroff, Matthias; Kleuss, Christiane; Wittig, Burghardt; Juhls, Christiane

doi:10.1016/j.vaccine.2010.03.034

Cited by 19 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The delivery of booster doses of vaccine resulted in no significant increase in antibody response that could be explained, at least partially, by the fact that DNA delivery system, used in this study, is known to drive a low level of antigen expression. Several investigators have reported that needle delivery of DNA vaccines in muscle induce low immune response in large animals and humans, even when 1000-fold higher doses of DNA than those proved to be effective in rodents were given [40], [41]. Other DNA vaccine delivery systems such as gene gun (biolistic gun) [42], [43], adenovirus or vaccinia virus delivery vectors [44], replicating attenuated strains of intracellular microorganisms, such as Salmonella [45] have shown promising results in eliciting antigen expression.…”

Section: Discussionmentioning

confidence: 99%

Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs

et al. 2011

View full text Add to dashboard Cite

Background Trypanosoma cruzi, the etiologic agent of Chagas Disease, is a major vector borne health problem in Latin America and an emerging infectious disease in the United States.MethodsWe tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine (TcVac1) against experimental T. cruzi infection in a canine model. Dogs were immunized with antigen-encoding plasmids and cytokine adjuvants, and two weeks after the last immunization, challenged with T. cruzi trypomastigotes. We measured antibody responses by ELISA and haemagglutination assay, parasitemia and infectivity to triatomines by xenodiagnosis, and performed electrocardiography and histology to assess myocardial damage and tissue pathology.ResultsVaccination with TcVac1 elicited parasite-and antigen-specific IgM and IgG (IgG2>IgG1) responses. Upon challenge infection, TcVac1-vaccinated dogs, as compared to non-vaccinated controls dogs, responded to T. cruzi with a rapid expansion of antibody response, moderately enhanced CD8+ T cell proliferation and IFN-γ production, and suppression of phagocytes’ activity evidenced by decreased myeloperoxidase and nitrite levels. Subsequently, vaccinated dogs controlled the acute parasitemia by day 37 pi (44 dpi in non-vaccinated dogs), and exhibited a moderate decline in infectivity to triatomines. TcVac1-immunized dogs did not control the myocardial parasite burden and electrocardiographic and histopatholgic cardiac alterations that are the hallmarks of acute Chagas disease. During the chronic stage, TcVac1-vaccinated dogs exhibited a moderate decline in cardiac alterations determined by EKG and anatomo-/histo-pathological analysis while chronically-infected/non-vaccinated dogs continued to exhibit severe EKG alterations.ConclusionsOverall, these results demonstrated that TcVac1 provided a partial resistance to T. cruzi infection and Chagas disease, and provide an impetus to improve the vaccination strategy against Chagas disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The DNA was formulated with SAINT-18 and administered i.d. to induce strong immune responses [20]. The concentration of S protein-specific antibodies was determined by ELISA in sera collected 14 days post boost immunization.…”

Section: Resultsmentioning

confidence: 99%

“…Delivery of naked HBsAg-encoding DNA vectors by needle and syringe has been reported to induce only weak immune responses in contrast to delivery by electroporation, emphasizing the need for a delivery system to enhance the efficacy of DNA vaccination. Based on our previous studies in mice [20] we hypothesized that formulation with SAINT-18 is an efficient delivery method for MIDGE-Th1 vectors in pigs as well.…”

Section: Discussionmentioning

confidence: 99%

“…On test day 35, blood was collected from the retrobulbar venous plexus under ether anaesthesia and animals were sacrificed by cutting the aorta abdominalis . Sera were obtained and HBsAg specific IgG1 and IgG2a antibodies determined as previously described [20]. The detection limit of the ELISA was 39 pg/ml for IgG1 and IgG2a.…”

Section: Methodsmentioning

confidence: 99%

“…Immunization with MIDGE-Th1 vectors elicits strong humoral and cellular immune responses [17], [18]. When formulated with the cationic lipid SAINT-18 [19], MIDGE-Th1 DNA vaccines induce significantly increased antibody responses against the S protein of HBsAg in mice [20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cationic Lipid-Formulated DNA Vaccine against Hepatitis B Virus: Immunogenicity of MIDGE-Th1 Vectors Encoding Small and Large Surface Antigen in Comparison to a Licensed Protein Vaccine

et al. 2014

Self Cite

View full text Add to dashboard Cite

Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L) protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.

show abstract

Mutation detection in plasmid‐based biopharmaceuticals

Oliveira

Prather

Prazeres

et al. 2011

Biotechnology Journal

View full text Add to dashboard Cite

As the number of applications involving therapeutic plasmid DNA (pDNA) increases worldwide, there is a growing concern over maintaining rigorous quality control through a panel of high-quality assays. For this reason, efficient, cost-effective and sensitive technologies enabling the identification of genetic variants and unwanted side products are needed to successfully establish the identity and stability of a plasmid-based biopharmaceutical. This review highlights several bioinformatic tools for ab initio detection of potentially unstable DNA regions, as well as techniques used for mutation detection in nucleic acids, with particular emphasis on pDNA.

show abstract

Immune response induced by a linear DNA vector: Influence of dose, formulation and route of injection

Cited by 19 publications

References 45 publications

Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs

Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs

Cationic Lipid-Formulated DNA Vaccine against Hepatitis B Virus: Immunogenicity of MIDGE-Th1 Vectors Encoding Small and Large Surface Antigen in Comparison to a Licensed Protein Vaccine

Mutation detection in plasmid‐based biopharmaceuticals

Contact Info

Product

Resources

About