Recent progress in synthetic self-adjuvanting vaccine development

Ariawan, A. Daryl; Eersel, Janet van; Martin, Adam D.; Ke, Yazi D.; Ittner, Lars M.

doi:10.1039/d2bm00061j

Cited by 8 publications

(3 citation statements)

References 129 publications

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“…In recent years, there has been increasing interest in the development of self-adjuvant nanomaterials for DNA vaccines ( 39 ). These nanomaterials possess intrinsic adjuvant properties, eliminating the need for additional adjuvant components.…”

Section: Current Status and Challenges Of Dna Vaccinementioning

confidence: 99%

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

Lu,

Lim,

et al. 2024

Front. Immunol.

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Vaccines have proven effective in the treatment and prevention of numerous diseases. However, traditional attenuated and inactivated vaccines suffer from certain drawbacks such as complex preparation, limited efficacy, potential risks and others. These limitations restrict their widespread use, especially in the face of an increasingly diverse range of diseases. With the ongoing advancements in genetic engineering vaccines, DNA vaccines have emerged as a highly promising approach in the treatment of both genetic diseases and acquired diseases. While several DNA vaccines have demonstrated substantial success in animal models of diseases, certain challenges need to be addressed before application in human subjects. The primary obstacle lies in the absence of an optimal delivery system, which significantly hampers the immunogenicity of DNA vaccines. We conduct a comprehensive analysis of the current status and limitations of DNA vaccines by focusing on both viral and non-viral DNA delivery systems, as they play crucial roles in the exploration of novel DNA vaccines. We provide an evaluation of their strengths and weaknesses based on our critical assessment. Additionally, the review summarizes the most recent advancements and breakthroughs in pre-clinical and clinical studies, highlighting the need for further clinical trials in this rapidly evolving field.

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Section: Current Status and Challenges Of Dna Vaccinementioning

confidence: 99%

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

Lu,

Lim,

et al. 2024

Front. Immunol.

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“…New analytical methods to address these challenges are rapidly surging in the field. [24][25][26][27][28][29] Gas chromatography (GC) and high-performance liquid chromatography (HPLC) are commonly used separation techniques employed for lipids and adjuvants. GC can be used to characterize volatile components, whereas appropriate sample preparation is required for non-volatile components.…”

Section: Introductionmentioning

confidence: 99%

Digitally Enabled Generic Analytical Framework Accelerating the Pace of Liquid Chromatography Method Development for Vaccine Adjuvant Formulations

Hemida,

Barrientos,

Kinsey

et al. 2024

Preprint

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The growing use of adjuvants in the fast-paced formulation of new vaccines has created an unprecedented need for meaningful analytical assays that deliver reliable quantitative data from complex adjuvant and adjuvant-antigen mixtures. Due to their complex chemical and physical properties, method development for the separation of vaccine adjuvants is considered a highly challenging and laborious task. Reversed-phase liquid chromatography (RPLC) is among the most important tests in the (bio)pharmaceutical industry for release and stability indicating measurements including adjuvant content, identity, and purity profile. However, the time constraints of developing “on-demand” robust quantitative methods prior to each change in formulation can easily lead to sample analysis becoming a bottleneck in vaccine development. Herein a simple and efficient generic analytical framework capable of chromatographically resolving the most commonly used non-aluminum based adjuvants across academic and industrial sectors is introduced. This was designed to seek a more proactive approach for fast-paced assay development endeavors that evolved from extensive stationary phase screening in conjunction with multifactorial in silico simulations of adjuvant retention time (RT) as a function of gradient time, temperature, organic modifier blending, and buffer concentration. The multifactorial retention models yield 3D resolution maps with excellent baseline separation of all adjuvants in a single run, which was found to be very accurate, with differences between experimental and simulated retention times of less than 1%. The analytical framework described here also includes the introduction of a more versatile approach to method development by introducing a dynamic RT database for adjuvants covering the entire library of adjuvants with broad mechanisms of action across numerous vaccine formulations with excellent linearity, accuracy, precision, and specificity. The power of this framework was also demonstrated with numerous analytical assays that can be generated rapidly from simulations guiding vaccine processes in the development of new adjuvant formulations. Analytical assay in this work covers content, purity profile by RPLC-UV-CAD, and component identification (RPLC-MS) across complex vaccine formulations, including the use of surfactants (e.g., polysorbates), as well as their separation from adjuvant targets.

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“…However, many vaccine antigens have weak immunogenicity and are inadequate to induce protective immune responses. , Thus, adjuvants are needed in vaccines with the ability to elicit antigen-specific immune responses . Toll-like receptor (TLR) agonists, which serve as key components to trigger the innate immune system and generate antigen-specific T cell responses to fight against tumors , and viruses, , have been well documented for their adjuvant abilities.…”

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confidence: 99%

Formulation and Evaluation of Lipidized Imiquimod as an Effective Adjuvant

Yin

Deng

et al. 2023

ACS Infect. Dis.

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Adjuvants are essential for the induction of robust immune responses against vaccine antigens. Small-molecule TLR7 agonists hold high potential for this purpose. In this communication, imiquimod (IMQ) bearing a cholesterol lipid moiety derivative, IMQ-Chol, was designed and synthesized as a vaccine adjuvant, which could release parent IMQ molecules in aqueous conditions via amide bond hydrolysis. We performed a series of immunological evaluations by cooperating with the inactivated foot-and-mouth disease virus (FMDV). All of the results confirmed that IMQ-Chol could stimulate the body for a prolonged time to produce strong humoral and cellular immunity with a balanced Th1/Th2 immune response through a TLR7-related MAPK pathway. In addition, the results of the proof-of-concept vaccine indicated IMQ-Chol had a good effect on preventing and treating FMD in pigs.

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Recent progress in synthetic self-adjuvanting vaccine development

Abstract: Vaccination is a proven way to protect individuals against many infectious diseases, as currently highlighted in the global COVID-19 pandemic. Peptides- or small molecule antigen-based vaccination offer advantages over the...

Cited by 8 publications

References 129 publications

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects

Digitally Enabled Generic Analytical Framework Accelerating the Pace of Liquid Chromatography Method Development for Vaccine Adjuvant Formulations

Formulation and Evaluation of Lipidized Imiquimod as an Effective Adjuvant

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