Microneedle arrays delivery of the conventional vaccines based on nonvirulent viruses

Abstract

Recently, microneedle arrays (MAs) have been developed for painless inoculation of vaccines and possess many prominent advantages, including convenience for inoculation, and exact delivery of vaccine to the exact epidermal and dermal or mucosal compartments which teem with antigen-presenting cells (APCs). Among different types of MAs, while the micro-environmental stimulus-responsive MAs represent one of the developmental trends in the field, the MAs combined with the conventional vaccines that are based on nonvirulent viruses, such as live attenuated or whole inactivated viruses, and antigen-encoding DNA viral vectors, have developed rapidly into the advanced stages, with certain products already on clinical trials. The pre- and clinical research outcomes showed that the painless MA delivery of the conventional vaccines through mammalian skin or mucosa can not only elicit robust systemic and even mucosal immunity to pathogens but also, in certain circumstances, redirect the immune response toward a specific Th1 pathway, resulting in cytotoxic T lymphocytes (CTL) to erase the cell-hidden pathogens, thanks to the robust adjuvant function of MAs exerted through damaging the contacted cells to release dangerous signals. This paper focuses on reviewing the latest research and advancements in MA delivery of the conventional vaccines that are based on nonvirulent viruses, underlining MA enhancement of the overall vaccine performance and the most advanced MA vaccine products that are relatively close to markets.

Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization

“…However, lack of other components of a pathogen, which may not only play a role in protection of antigens but also act as a type of PAMP/DAMP, often makes subunit vaccines vulnerable to environmental damages and ineffective in triggering immunoresponses toward Ags [54,55]. To enhance the potency of subunit vaccines, researchers have developed various types of particulate carriers, such as liposomes, cochleates, virosomes, emulsions, lipid and polymeric NPs, some of which are constructed in just the manner of mimicking the structure of pathogenic organisms to carry, protect and deliver vaccines, thus promoting their immunostimulatory activities [14,17,29,53,56]. Also, these particulate carriers are often additionally incorporated with functional molecules, such as TLRas (toll-like receptor agonists/ligands), CLRas (C-type lectin receptor agonist/ligands), NLRas (NOD-like receptor agonists/ligands), saponin and squalene and their derivatives, and various environmental stimulussensitive molecules, to further expand their functions [57,58].…”

“…Notably, many studies on liposome VADSs have actually reported the Ag release data [15,56,59,61], however, the direct relationship between the Ag release features and the induced immunity quality has rarely been elucidated. Moreover, these investigations on Ag release were mostly conducted with in vitro experiments, which can hardly reflect the real profile that liposomes will manifest under in vivo circumstances.…”

Bioresponsive transcutaneous patches

“…Recently, transdermal patch models that incorporate stimuli-responsive MNs which release drug in response to an internally-generated stimuli have been proposed for smart and precise drug release [10–13]. Compared to delivery systems triggered by external stimuli like electric field [14,15], light [16,17], or mechanical force [18], the MN patches activated by a physiological signal provide self-regulated delivery of drug in response to the abnormal physiological signals, thereby maximizing therapeutic efficiency and minimizing side effects or toxicity [19].…”

Liposomes Used as a Vaccine Adjuvant-Delivery System

“…Unfortunately, due to lack of other microbial components, which may not only protect the antigens but also be a pathogen-associated molecular pattern (PAMP) for mammalian immune systems, the subunit vaccines are usually unstable and often induce insufficient immune responses against pathogens [9,10]. To overcome these weaknesses of subunit vaccines, numerous types of nanoparticles with composition mimicking the components of pathogenic organisms have been developed as a vaccine carrier forming the so-called vaccine adjuvant-delivery systems (VADSs), which can protect antigens from the environmental damage, deliver ingredients to specific lymphocytes, and even enhance, as an adjuvant, the initiation of Ag-specific immune responses [8,[11][12][13][14].…”

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