Needle-Free Immunization with Chitosan-Based Systems

Abstract

Despite successful use, needle-based immunizations have several issues such as the risk of injuries and infections from the reuse of needles and syringes and the low patient compliance due to pain and fear of needles during immunization. In contrast, needle-free immunizations have several advantages including ease of administration, high level of patient compliance and the possibility of mass vaccination. Thus, there is an increasing interest on developing effective needle-free immunizations via cutaneous and mucosal approaches. Here, we discuss several methods of needle-free immunizations and provide insights into promising use of chitosan systems for successful immunization.

Keywords: chitosan; mucosal vaccine; needle-free immunization.

Figure 1

Immunization by cutaneous routes. A. Liquid-jet injection delivers vaccine to muscular, subcutaneous or dermal regions, depending on the parameters of the injection, B. Epidermal powder immunization delivers vaccine powders to the superficial layers of the skin, C. Topical application of vaccines delivers vaccines to the epidermis, where they are recognized and processed by Langerhans cells. Immunization by topical vaccine application is facilitated by several methods (a–h) (Reprinted with permission from Ref. [1]).

Figure 2

Mucosal immunization routes and compartmentalization of effector functions. Within the mucosa-associated lymphoid tissue (MALT), sub compartments can be identified, such as the nasopharynx-associated lymphoid tissue (NALT), bronchus-associated lymphoid tissue (BALT), gut-associated lymphoid tissue (GALT) and genital tract-associated lymphoid tissue. Certain immunization routes are more effective at stimulating immunity within specific, most often closely located, sub compartments of the MALT. Intranasal vaccination is preferred for targeting the respiratory, gastric and genital tracts; oral vaccination is effective for immunity in the gut and for the induction of mammary gland antibodies (which are secreted in milk); rectal immunization is best for the induction of colon and rectal immunity and to some extent genital tract immunity; and intravaginal vaccination is the most effective for antibody and T cell immunity in the genital tract. (Reprinted with permission from Ref. [3]).

Figure 3

Schematic diagram of various immune responses induced by particulate vaccine system. Upon encounter with an antigen, B cells convert themselves to antibody secreting plasma cells that produce antibodies for excreting the pathogens to mucosal surfaces (mucosal response) whereas dendritic cells (DCs) present the antigen via major histocompatibility complex (MHC) class I and class II molecules to CD8+ and CD4+ T-cells. Activation pathway of CD8+ T cells and CD4+ Th1 cells produces cytotoxic T lymphocytes (CTL) and activated macrophages that kill intracellular pathogens or infected cells (cellular response) while activation pathway of CD4+ Th2 cells produces activated B lymphocytes that secrete antibodies for neutralization of extracellular pathogens (humoral response) (Reprinted with permission from Ref. [6]).

Figure 4

Microneedle patch (MNP) for influenza vaccination. (a) The MNP contains an array of 100 microneedles measuring 650 μm tall that is mounted on an adhesive backing. (b) The MNP is manually administered to the wrist, enabling self-administration by study subjects. (c) Microneedles encapsulate influenza vaccine (represented here by blue dye) within a water-soluble matrix. (d) After application to the skin, the microneedles dissolve, thereby depositing vaccine in the skin and leaving behind a patch backing that can be discarded as non-sharps waste. (Reprinted with permission from Ref. [81]).

Figure 5

(A) Schematic illustrations of sustained transdermal delivery of antigen using a microneedle delivery system, composed of embeddable chitosan microneedles (MNs) and a poly(l-lactide-co-d,l-lactide) (PLA) supporting array. (B) OVA-specific IgG levels of rats after a single dose of antigen: non-immunized group (saline), intramuscularly immunized (IM, 1 mg OVA) and microneedle-immunized (MN, 1 mg OVA/array) rats (n = 3 for each group). (Reprinted with permission from Ref. [83]).

Figure 6

Anti-BBD IgA levels in (A) nasal wash; (B) saliva; (C) serum and (D) anti-BBD IgG levels in serum (data are means ± standard deviations, n = 3). Significant differences between untreated and immunized groups was expressed as * p < 0.001 and ** p < 0.05 and between BBD-CMs and BBD-MCMs groups as ^## p < 0.05. (Reprinted with permission from Ref. [116]).

Figure 7

BmpB-specific immune response detection by ELISA after oral administration. Anti-BmpB IgA levels in feces (A) and intestine (B), anti-BmpB IgG levels in serum (C) and anti-BmpB IgG1 and IgG2a (D) levels. (Reprinted with permission from Ref. [131]).