Plasmid DNA vaccines: where are we now?

2018 ◽  
Vol 54 (5) ◽  
pp. 315 ◽  
Author(s):  
F. Ghaffarifar
Keyword(s):  
2005 ◽  
Vol 86 (3) ◽  
pp. 601-610 ◽  
Author(s):  
Xiao-Wen He ◽  
Fang Wang ◽  
Lei Jiang ◽  
Jun Li ◽  
Shan-kui Liu ◽  
...  

The purpose of this work was to assess the ability of plasmid DNA encoding hepatitis B virus (HBV) HBsAg encapsulated in poly(dl-lactide-co-glycolic acid) (PLGA) microparticles to induce local and systemic HBsAg-specific immunity following a single dose of oral immunization. RT-PCR analysis demonstrated prolonged transcription of plasmid DNA, consistent with the sustained expression and presentation of target antigen observed by confocal laser scanning microscopy, in gut-associated lymphocyte tissue (GALT) from mice immunized orally with plasmid DNA encapsulated into PLGA microparticles. Oral administration of PLGA-DNA microparticles induced a long-lasting and stable antigen-specific antibody response, both serum total antibody and intestinal IgA, in BALB/c mice. Mice immunized orally exhibited antigen-specific gamma interferon production and cytotoxic T lymphocyte responses in spleen and GALT after restimulation in vitro with HBsAg or tumour cells stably expressing HBsAg. In contrast, naked DNA vaccines given by intramuscular injection induced only systemic cellular and humoral responses to HBsAg, which were much lower than the responses elicited by oral DNA encapsulated in PLGA microparticles at equivalent doses. The results are encouraging with regard to obtaining good compliance and vaccination coverage with candidate plasmid DNA vaccines, especially in developing countries.


Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 37 ◽  
Author(s):  
Liu

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.


Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1737-1745 ◽  
Author(s):  
Patricia A. Johnson ◽  
Margaret A. Conway ◽  
Janet Daly ◽  
Carolyn Nicolson ◽  
James Robertson ◽  
...  

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.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 30 ◽  
Author(s):  
Michael Lim ◽  
Abu Zayed Md Badruddoza ◽  
Jannatul Firdous ◽  
Mohammad Azad ◽  
Adnan Mannan ◽  
...  

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.


2014 ◽  
Vol 13 (12) ◽  
pp. 1537-1551 ◽  
Author(s):  
Alex Xenopoulos ◽  
Priyabrata Pattnaik
Keyword(s):  

2020 ◽  
Author(s):  
Shuaikai Ren ◽  
Liang Guo ◽  
Chunxin Wang ◽  
Jiaxi Ru ◽  
Yunqi Yang ◽  
...  

Abstract Background: Nanotechnology represents a new impetus for biomedical research applications, especially using nanotechnology to formulate microspheres or nanospheres based delivery system for treatment of infectious diseases in animals.Results: Polylactic acid (PLA) microspheres with an average size of 156nm were prepared by combining emulsion polymerization coupled with emulsion−solvent evaporation. Coating with three different molecular weights of polyethylenimine (PEI) polymers increased the surface charges of the resulting PLA/PEI microspheres. Electrostatic interactions enabled plasmid DNA to adsorb tightly to the microspheres. After pig kidney-15 cells were cultured with the PLA/PEI/DNA complexes for 48 h, all three PLA/PEI microspheres successfully transferred plasmid DNA into the cells with high transfection efficiency. The protection rate of PLA/PEI microspheres loaded with DNA vaccine against foot-and-mouth disease in guinea pigs reached 87.5%, which was significantly higher than that of the control group injected with only DNA vaccine.Conclusions: In this work, PLA/PEI microspheres were constructed by preparing PLA microspheres and modifying with PEI polymers, and were shown a great potential in improve the efficacy, biosafety and economic effects of DNA vaccines. The results indicated PLA/PEI microspheres were expected to be an effective delivery system for DNA vaccines.


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