scholarly journals Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 30 ◽  
Author(s):  
Michael Lim ◽  
Abu Zayed Md Badruddoza ◽  
Jannatul Firdous ◽  
Mohammad Azad ◽  
Adnan Mannan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Clinical Application ◽  
Dna Vaccine ◽  
Immune Cells ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Immunological Response ◽  
Main Challenge ◽  
Human Immunodeficiency Viruses ◽  
Stimulation Of

DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date. The main challenge that hinders the progress of DNA vaccines and limits their clinical application is the delivery hurdles to targeted immune cells, which obstructs the stimulation of robust antigen-specific immune responses in humans. In this updated review, we discuss various nanodelivery systems that improve DNA vaccine technologies to enhance the immunological response against target diseases. We also provide possible perspectives on how we can bring this exciting vaccine technology to bedside applications.

scholarly journals Plasmid Chemokines and Colony-Stimulating Factors Enhance the Immunogenicity of DNA Priming-Viral Vector Boosting Human Immunodeficiency Virus Type 1 Vaccines

2003 ◽  
Vol 77 (16) ◽  
pp. 8729-8735 ◽  
Author(s):  
Dan H. Barouch ◽  
Paul F. McKay ◽  
Shawn M. Sumida ◽  
Sampa Santra ◽  
Shawn S. Jackson ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Viral Vectors ◽  
Dna Vaccines ◽  
Viral Vector ◽  
Human Populations ◽  
Colony Stimulating Factors ◽  
Boost Vaccine ◽  
Vector Boosting

ABSTRACT Heterologous “prime-boost” regimens that involve priming with plasmid DNA vaccines and boosting with recombinant viral vectors have been shown to elicit potent virus-specific cytotoxic T-lymphocyte responses. Increasing evidence, however, suggests that the utility of recombinant viral vectors in human populations will be significantly limited by preexisting antivector immunity. Here we demonstrate that the coadministration of plasmid chemokines and colony-stimulating factors with plasmid DNA vaccines markedly increases the immunogenicity of DNA prime-recombinant adenovirus serotype 5 (rAd5) boost and DNA prime-recombinant vaccinia virus (rVac) boost vaccine regimens in BALB/c mice. In mice with preexisting anti-Ad5 immunity, priming with the DNA vaccine alone followed by rAd5 boosting elicited only marginal immune responses. In contrast, cytokine-augmented DNA vaccine priming followed by rAd5 vector boosting was able to generate potent immune responses in mice with preexisting anti-Ad5 immunity. These data demonstrate that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity.

scholarly journals A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 37 ◽  
Author(s):  
Liu
Keyword(s):  
Clinical Trials ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Delivery Systems ◽  
Potential Toxicity ◽  
Vaccine Candidates ◽  
The Status ◽  
Experimental Findings ◽  
Theoretical Issues

This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.

Plasmid DNA encoding influenza virus haemagglutinin induces Th1 cells and protection against respiratory infection despite its limited ability to generate antibody responses

Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1737-1745 ◽  
Author(s):  
Patricia A. Johnson ◽  
Margaret A. Conway ◽  
Janet Daly ◽  
Carolyn Nicolson ◽  
James Robertson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Immune Responses ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Dose Range ◽  
Th1 Cells ◽  
Dna Encoding ◽  
Live Virus ◽  
Limited Ability

Direct intramuscular injection of plasmid DNA can generate immune responses against encoded antigens. However, the relative ability of DNA vaccines to induce cellular and humoral immunity after a single or booster immunization and the persistence of this response have not been fully elucidated. In this study, induction and maintenance of antibody and T cell subtypes with different doses of naked DNA encoding the haemagglutinin (HA) gene of influenza virus were examined and compared to the immune responses and protection induced by respiratory tract infection and immunization with a killed virus vaccine. Like natural infection, immunization with HA DNA induced potent Th1 responses. Spleen cells from mice immunized once with HA DNA in the dose range 10 ng to 100 μg secreted significant levels of IFN-γ, but low or undetectable IL-5, in response to influenza virus in vitro. Furthermore, CD4+ HA-specific Th1 clones were generated from spleens of immunized mice. Although T cell responses waned 12 weeks after a single immunization, antigen-specific Th1 cells persisted in the spleen for at least 6 months after two booster immunizations. In contrast, influenza virus-specific ELISA IgG titres were low after a single immunization and required two booster immunizations to reach significant levels. Furthermore, haemagglutination inhibition (HI) antibodies were weak or undetectable after two immunizations. Nevertheless, two doses of HA DNA conferred almost complete protection against respiratory challenge with live virus. Thus, despite the limited ability to induce antibodies, DNA vaccines confer protective immunity against influenza virus infection, which appears to be mediated by Th1 cells.

Enhancing immune responses against a plasmid DNA vaccine encoding a FMDV empty capsid from serotype O

Vaccine ◽  
2006 ◽  
Vol 24 (21) ◽  
pp. 4602-4606 ◽  
Author(s):  
Yanmin Li ◽  
Neeraj Aggarwal ◽  
Haru-H. Takamatsu ◽  
Catrina M.A. Sterling ◽  
Charlotte Voyce ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Serotype O ◽  
Empty Capsid ◽  
Plasmid Dna Vaccine

Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice

Vaccine ◽  
2006 ◽  
Vol 24 (21) ◽  
pp. 4510-4523 ◽  
Author(s):  
Michael A. Egan ◽  
Shakuntala Megati ◽  
Vidia Roopchand ◽  
Dorys Garcia-Hand ◽  
Amara Luckay ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Rational Design ◽  
Plasmid Dna Vaccine

Antitumor Effect of a DNA Vaccine Harboring Prostate Cancer-Specific Antigen with IL-12 as an Intramolecular Adjuvant

2017 ◽  
Vol 27 (3) ◽  
pp. 168-174 ◽  
Author(s):  
Yu Yang ◽  
Zhiqiang Shao ◽  
Jiangping Gao
Keyword(s):  
Prostate Cancer ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Dna Vaccines ◽  
Electric Pulse ◽  
Specific Antigen ◽  
Interleukin 12 ◽  
Cellular Immune Responses ◽  
Prostate Cancer Therapy ◽  
Cellular Immune

To improve the lower immune intensity of DNA vaccines, we developed a DNA vaccine based on prostate cancer-specific antigen (PSA), which has been suggested as a potential target for prostate cancer therapy, and enhanced the DNA vaccine potency using interleukin-12 (IL-12) as an intramolecular adjuvant. A series of DNA plasmids encoding human PSA, IL-12, and their conjugates was constructed and injected into female mice intramuscularly, followed by an electric pulse. The humoral and cellular immune responses after immunization were detected by ELISA and ELISPOT, respectively. To evaluate the therapeutic efficacy of these plasmids, a mouse model with a PSA-expressing tumor was constructed. Mice vaccinated with PSA-IL-12 plasmids elicited the strongest PSA-specific humoral and cellular immune responses. Furthermore, these vaccinations inhibited the growth of PSA-expressing tumors and prolonged mouse survival. These observations emphasize the potential of the IL-12 gene as an intramolecular adjuvant for DNA vaccines. Moreover, the vaccine based on PSA and IL-12 may be a promising treatment for prostate cancer.

scholarly journals Neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses in patients with triple negative breast cancer

2021 ◽  
Author(s):  
Xiuli Zhang ◽  
S. Peter Goedegebuure ◽  
Nancy Myers ◽  
Tammy Vickery ◽  
Michael McLellan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Dna Vaccines ◽  
Laboratory Evaluation ◽  
Minimal Risk ◽  
Free Survival

PURPOSE: Cancer neoantigens are important targets of cancer immunotherapy. Neoantigen vaccines have the potential to induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes. To test the safety, feasibility and efficacy of this platform, we performed a phase 1 clinical trial in triple negative breast cancer patients with persistent disease following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence. EXPERIMENTAL DESIGN: Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite was used to identify and prioritize cancer neoantigens. Neoantigen DNA vaccines were designed and manufactured in an academic GMP facility at Washington University School of Medicine. Neoantigen DNA vaccines were administered via electroporation following completion of standard of care therapy. Safety was measured by clinical and laboratory evaluation. Immune responses were assessed by ELISPOT, flow cytometry and TCR sequencing. RESULTS: 18 subjects received three doses of a personalized neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4-20). The vaccinations were well tolerated with limited adverse events, primarily related to injection site reactions. Neoantigen-specific immune responses were induced in 16/18 patients as measured by ELISPOT and flow cytometry. At a median follow-up of 36 months, progression-free survival was 87.5% (95% CI: 72.7-100%) in the cohort of vaccinated patients compared to 49% (95% CI: 36.4-65.9%) in a cohort of institutional historical control patients (p=0.011). CONCLUSIONS: Neoantigen DNA vaccines are safe, feasible, and capable of inducing a neoantigen-specific immune response. There is preliminary evidence of improved disease-free survival compared to historical controls.

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