Methods to improve the immunogenicity of plasmid DNA vaccines

Eusébio, Dalinda; Neves, Ana R.; Costa, Diana; Biswas, Swati; Alves, Gilberto; Cui, Zhengrong; Sousa, Ângela

doi:10.1016/j.drudis.2021.06.008

Cited by 58 publications

(59 citation statements)

References 115 publications

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“…On the other hand, one concern of development of DNA vaccine using plasmid DNA, especially in human clinical trials, is weak immunogenicity [ 11 , 12 ]. To overcome this limitation, many administrative conditions such as administrative routes, adjuvants have been explored to improve the efficacy of DNA vaccine [13] . In this study, we developed DNA-based vaccine targeting the SARS-CoV-2 spike glycoprotein.…”

Section: Introductionmentioning

confidence: 99%

Preclinical study of a DNA vaccine targeting SARS-CoV-2

Hayashi

Sun

Yanagida

et al. 2022

Current Research in Translational Medicine

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Section: Introductionmentioning

confidence: 99%

Preclinical study of a DNA vaccine targeting SARS-CoV-2

Hayashi

Sun

Yanagida

et al. 2022

Current Research in Translational Medicine

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“…It has the advantages of easy handling (such as storage and transport due to its high stability) and easy mass production. As a DNA vaccine, it can be used for treating infectious disease or cancer by encoding tumor-associated antigen (Lopes et al 2019 ; Eusébio et al 2021 ). Plasmid DNA has been studied in various applications such as regenerative medicine using induced pluripotent stem cells (iPSCs) by transfecting plasmid DNA encoding reprogramming factors like Yamanaka factor (Karow et al 2011 ).…”

Section: Nucleic Acid Drugsmentioning

confidence: 99%

Microneedle systems for delivering nucleic acid drugs

Noh

Lee

Rhee

2022

J. Pharm. Investig.

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Background Nucleic acid-based gene therapy is a promising technology that has been used in various applications such as novel vaccination platforms for infectious/cancer diseases and cellular reprogramming because of its fast, specific, and effective properties. Despite its potential, the parenteral nucleic acid drug formulation exhibits instability and low efficacy due to various barriers, such as stability concerns related to its liquid state formulation, skin barriers, and endogenous nuclease degradation. As promising alternatives, many attempts have been made to perform nucleic acid delivery using a microneedle system. With its minimal invasiveness, microneedle can deliver nucleic acid drugs with enhanced efficacy and improved stability. Area covered This review describes nucleic acid medicines' current state and features and their delivery systems utilizing non-viral vectors and physical delivery systems. In addition, different types of microneedle delivery systems and their properties are briefly reviewed. Furthermore, recent advances of microneedle-based nucleic acid drugs, including featured vaccination applications, are described. Expert opinion Nucleic acid drugs have shown significant potential beyond the limitation of conventional small molecules, and the current COVID-19 pandemic highlights the importance of nucleic acid therapies as a novel vaccination platform. Microneedle-mediated nucleic acid drug delivery is a potential platform for less invasive nucleic acid drug delivery. Microneedle system can show enhanced efficacy, stability, and improved patient convenience through self-administration with less pain.

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“…), chemical methods (liposome, synthetic polymer, etc.) and adjuvants have been explored to improve the immunogenicity of DNA vaccine ( 12 ). However, the extracellular and intracellular barriers that restrain the transportation of DNA into the nucleus have not been satisfactorily resolved ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Successive Site Translocating Inoculation Improved T Cell Responses Elicited by a DNA Vaccine Encoding SARS-CoV-2 S Protein

Tian

Zhang

et al. 2022

Front. Immunol.

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A variety of methods have been explored to increase delivery efficiencies for DNA vaccine. However, the immunogenicity of DNA vaccines has not been satisfactorily improved. Unlike most of the previous attempts, we provided evidence suggesting that changing the injection site successively (successively site-translocated inoculation, SSTI) could significantly enhance the immunogenicity of DNA vaccines in a previous study. To simplify the strategy and to evaluate its impact on candidate SARS-CoV-2 vaccines, we immunized mice with either a SARS-CoV-2 spike-based DNA vaccine or a spike protein subunit vaccine via three different inoculation strategies. Our data demonstrated that S protein specific antibody responses elicited by the DNA vaccine or the protein subunit vaccine showed no significant difference among different inoculation strategies. Of interest, compared with the conventional site fixed inoculation (SFI), both successive site-translocating inoculation (SSTI) and the simplified translocating inoculation (STI) strategy improved specific T cell responses elicited by the DNA vaccine. More specifically, the SSTI strategy significantly improved both the monofunctional (IFN-γ+IL-2-TNF-α-CD8+) and the multifunctional (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses, while the simplified translocating inoculation (STI) strategy significantly improved the multifunctional CD8+ (IFN-γ+IL-2-TNF-α+CD8+, IFN-γ+IL-2+TNF-α+CD8+) and CD4+ (IFN-γ+IL-2-TNF-α+CD4+, IFN-γ+IL-2+TNF-α+CD4+) T cell responses. The current study confirmed that changing the site of intra muscular injection can significantly improve the immunogenicity of DNA vaccines.

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Methods to improve the immunogenicity of plasmid DNA vaccines

Cited by 58 publications

References 115 publications

Preclinical study of a DNA vaccine targeting SARS-CoV-2

Preclinical study of a DNA vaccine targeting SARS-CoV-2

Microneedle systems for delivering nucleic acid drugs

Successive Site Translocating Inoculation Improved T Cell Responses Elicited by a DNA Vaccine Encoding SARS-CoV-2 S Protein

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