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Open AccessJournal ArticleDOI

Clinical Applications of DNA Vaccines: Current Progress

TLDR
The ability of the current, or second-generation, DNA vaccines to induce more-potent cellular and humoral responses opens up this platform to be examined in both preventative and therapeutic arenas.
Abstract
It was discovered almost 20 years ago that plasmid DNA, when injected into the skin or muscle of mice, could induce immune responses to encoded antigens. Since that time, there has since been much progress in understanding the basic biology behind this deceptively simple vaccine platform and much technological advancement to enhance immune potency. Among these advancements are improved formulations and improved physical methods of delivery, which increase the uptake of vaccine plasmids by cells; optimization of vaccine vectors and encoded antigens; and the development of novel formulations and adjuvants to augment and direct the host immune response. The ability of the current, or second-generation, DNA vaccines to induce more-potent cellular and humoral responses opens up this platform to be examined in both preventative and therapeutic arenas. This review focuses on these advances and discusses both preventive and immunotherapeutic clinical applications.

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mRNA vaccine delivery using lipid nanoparticles.

TL;DR: Among potential nonviral vectors, lipid nanoparticles are particularly promising, and can be synthesized with relative ease in a scalable manner, protect the mRNA against degradation, facilitate endosomal escape, and as needed, can be codelivered with adjuvants.
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Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines

TL;DR: Screening a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model shows that mRNA vaccine tolerability can be improved without affecting potency.
Journal ArticleDOI

Vaccines for the 21st century.

TL;DR: The state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer are reviewed and the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure‐based antigen design are described.
Journal ArticleDOI

Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.

TL;DR: In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells and led to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks.
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Journal Article

Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a Phase I study of ZYC101.

TL;DR: Ten of 12 subjects demonstrated increased immune response to the peptide epitopes encoded within ZYC101; each continued to show elevated immune responses 6 months after the initiation of therapy, which support the continued investigation of a therapeutic vaccination strategy for anal dysplasia.
Journal ArticleDOI

Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design

TL;DR: Persistent immunity to the 1918 flu or its close relatives from childhood may inhibit the unprotected spike protein of the current 2009 pandemic flu virus and, thus, its ability to infect host cells.
Journal ArticleDOI

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

TL;DR: It is demonstrated that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cell-mediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.
Journal ArticleDOI

A Phase I Trial of a Human Papillomavirus DNA Vaccine for HPV16+ Cervical Intraepithelial Neoplasia 2/3

TL;DR: It seems possible to elicit HPV-specific T-cell responses in patients with established dysplastic lesions, and other factors are likely to play a role in lesion regression.
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