Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS)

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

“…Moreover, liposomes have long been confirmed of the intrinsic adjuvanticities and, unlike other adjuvants, have showed minimal reactogenicity, therefore rarely causing hypersensitivity-associated reactions in immunized subjects [24][25][26]. In addition, it is argued that liposomes can always play well the role of an adjuvant regardless of the Ag loading mode of being entrapped within, attached onto, or even simply admixed with the vesicles, thus greatly simplifying the product manufacturing procedure owing to omitting a tedious step of removing free Ags [27,28]. Also, liposomes have been extensively explored to be combined with a variety of functional molecules, such as the ones bearing a PAMP/ DAMP feature able to binding to certain PRRs, and the ones matching the receptors expressed on APCs to facilitate APC uptake of vaccines [16,17,[29][30][31].…”

Liposomes Used as a Vaccine Adjuvant-Delivery System

“…For in-vivo imaging, usually, 0.5, 1, 2, 4, and 8 h after administration of the fluorescent agent/ Ag-loaded liposomes via intradermal, intramuscular, intra-mucosal or any other feasible route, mouse is imaged using animal in vivo imaging systems; otherwise, mouse is exposed, by anesthetic and anatomic operation, of mucosa, lymph nodes (LNs), or other region wherein vaccines are expected to be delivered by liposomes, to lights with the wavelength matching fluorescent agent entrapped in liposomes for automatic imaging using a camera or a smart phone with lens [24].…”

“…In the ensuing years, extensive work in this laboratory and elsewhere has shown that liposomal adjuvanticity applies to a wide variety of bacterial, viral, protozoan, tumor, and other antigens [19,22]. Now it is generally accepted that liposome can always function the role of adjuvanticity regardless of the type of association of the antigen with liposomes, such as being entrapped within the vesicles, attached onto their surface, and even simply mixed together [23,24]. To be efficiently recognized and thus taken up by antigen-presenting cells (APCs), liposomes have been explored to be decorated with PAMP molecules and/or the molecules as ligands matching the receptors expressed on the surface of the aimed immunocytes, thus forming a multifunctional targeting VADS [11,12,[25][26][27].…”

“…To date, various multifunctional liposomes have been developed as a novel VADS targeting APCs to enhance vaccine immunostimulating capacity by utilizing the specific binding affinities between functional molecules on the carrier and special features expressed or engendered by the immune cells. For example, recently, multifunctional liposomes have been successfully constructed being anchored with a toll-like receptor (TLR) ligands, including lipid A for TLR4, CpG-ODN for TLR9, and the synthetic molecules with a distal of mannose group for the C-type receptors on APCs, such as dendritic cells (DCs), macrophages (MPs), and even been fabricated into microneedles for penetration of skin and mucosa to further enhance delivery efficiency [24]. These kinds of multifunctional liposomes as a VADS proved highly effective in both targeting delivery of vaccine to APCs and enhancing antigen presentation of APCs to T-cells fulfilling a dual function of delivery and adjuvancy for vaccines [11,24,25,27,28].…”

“…The in vivo Ag-specific cytolysis of induced CTLs in the vaccine-treated mice is regarded as the Ag-specific cytotoxicity of CTLs and is often analyzed using the CFSE-labeled cells bearing the Ag epitopes [57]. Herein, using OVA as the model Ag, the process for assay of the Ag-specific cytotoxicity of CTLs in the vaccinated mice is described as follows [24]:…”