Technologies for enhanced efficacy of DNA vaccines

Saade, Fadi; Petrovsky, Nikolai

doi:10.1586/erv.11.188

Cited by 272 publications

(236 citation statements)

References 215 publications

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“…Furthermore, our study showed that the pCI-IL-6 co-immunized mice developed more potent cell-mediated immune responses, as evidenced by the higher levels of splenocyte IFN-γ production when re-stimulated with PAc. IFN-γ and IL-4 are Th1-type and Th2-type cytokines, respectively, and the former represents the cell-mediated immune response [35] , whereas the latter represents the humoral immune response [36] . Although the reason for Th1 biased T-cell induction rather than Th2 biased T-cell stimulation remains unknown, previous studies may partially explain the cause of T-cell differentiation after DNA vaccination.…”

Section: Discussionmentioning

confidence: 99%

Intranasal co-delivery of IL-6 gene enhances the immunogenicity of anti-caries DNA vaccine

et al. 2014

Acta Pharmacol Sin

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Aim: To investigate the effects of co-delivering IL-6 expressing plasmid pCI-IL-6 on the immunogenicity of the anti-caries DNA vaccine pCIA-P, which encodes the surface protein antigen PAc of Streptococcus mutans. Methods: Plasmid pCI-IL-6 was constructed by inserting the murine IL-6 gene into the pCI vector. Expression of IL-6 in vitro was assessed using Western blot analysis. BALB/c mice were intranasally co-immunized with pCIA-P plus pCI-IL-6 on d 0 and 14. Anti-PAc IgG and secretory IgA (sIgA) were assessed by ELISA. Splenocytes from the mice were re-stimulated with the PAc protein, and IFN-γ and IL-4 production was measured using ELISA. Splenocyte proliferation was analyzed with flow cytometry. Rats were similarly immunized, and dental caries scores were determined using the Keyes method. Results: Marked expression of IL-6 was found in COS-7 cells transfected with pCI-IL-6. In the pCI-IL-6 co-immunized mice, the specific IgG antibodies in serum and sIgA antibodies in saliva were significantly higher than those in the control mice at weeks 4 and 8. Moreover, the secretion of IFN-γ from splenocytes in response to re-stimulation with PAc protein was significantly higher in the pCI-IL-6 co-immunized mice than that in the control mice, whereas the secretion of IL-4 had no significant difference. The proliferation of splenocytes from the pCI-IL-6 co-immunized mice was significantly higher than that from the mice immunized with pCIA-P and pCI vector. In the rat caries model, the pCI-IL-6 co-immunization rats displayed lower caries scores than the control rats. Conclusion: Intranasal co-delivery of IL-6 gene significantly enhances the immunogenicity of the anti-caries DNA vaccine.

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Section: Discussionmentioning

confidence: 99%

Intranasal co-delivery of IL-6 gene enhances the immunogenicity of anti-caries DNA vaccine

et al. 2014

Acta Pharmacol Sin

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“…One of the limitations of this type of technology is that it normally induces a Th2 type of response, at least in mice and in non-human primates [78]. Needle-free devices such as Biojector ® have also been developed and a more comprehensive review of this technology can be found in [79].…”

Section: Phase I Nct01922284mentioning

confidence: 99%

“…Besides the substances discussed previously, chemokines, signaling and co-stimulatory molecules have also been tested and a very detailed review is available in [79].…”

Section: Adjuvantsmentioning

confidence: 99%

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

Rosa¹

2015

J Vaccines Vaccin

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Vaccination has been the most efficacious way to combat infectious diseases in human history. Nevertheless, there are still a variety of pathogens for which vaccines are urgently needed. In the last 25 years, DNA vaccines emerged as promising in prophylactic and therapeutic settings. However, despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific immune responses and protection in humans. In the last years, rational approaches to improve the efficacy of DNA vaccines were developed and include: modifications of plasmid basic design, use of next-generation delivery methods, addition of adjuvants in the formulation, improvement in immunization protocols and even targeting to dendritic cells. In this review, we will explore the advances and hurdles involved in the development of more potent DNA vaccines.

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“…Moreover, the production costs are relatively low, and the DNA is stable and does not require refrigeration for storage. 20,21 Several DNA vaccine formulations containing the F, G and matrix protein (M2) either alone or in combination were tested in animal models.…”

Section: Introductionmentioning

confidence: 99%

Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency

Farrag

Amer

Öhlschläger

et al. 2017

Human Vaccines & Immunotherapeutics

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The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codonoptimized HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M2 82-90 linked (pPOE-FM2) forms of the F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for recombinant vectors to elicit significant levels of neutralizing antibodies and CD8 C T-cell lymphocytes. pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and cellular immune responses. Following virus challenge, mice that had been immunized with the recombinant vectors were able to control virus replication and displayed lower inflammation compared with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover, pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage further evaluation in phase I clinical trials.

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Technologies for enhanced efficacy of DNA vaccines

Cited by 272 publications

References 215 publications

Intranasal co-delivery of IL-6 gene enhances the immunogenicity of anti-caries DNA vaccine

Intranasal co-delivery of IL-6 gene enhances the immunogenicity of anti-caries DNA vaccine

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency

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