Pharmaceutical Manufacturing Handbook: Production and

NASAL DELIVERY OF VACCINES 635
However, the nasal epithelium has little ability to break down drugs. The extensive
mucosal surface of the nose has a lining of pseudostratifi ed epithelium as well as
cilia and the goblet cells involved in the secretion of mucus. The lymphoid tissue
primarily involved in the mucosal immune responses is the mucosal - associated
lymphoid tissue (MALT). The different regions of the respiratory tract that play an
infl uencing role in the immune system are as follows:
• The epithelial surface, which comprises immunocompetent cells in the connective
tissue
• The lymphoid tissues linked to the respiratory tract, which are categorized into
three parts: larynx - associated lymphoid tissue (LALT), nose - associated lymphoid
tissue (NALT), and bronchus - associated lymphoid tissue
• The lymph nodes that drain the respiratory tract
The NALT, which is the organized lymphoid structure in the nasal passages and
occurs in abundance in the nasal mucosa, plays a signifi cant role in the mucosal
surface ’ s defense against invading pathogens. The NALT is equivalent to Waldeyer ’ s
ring, which is made up of the adenoids or tonsils situated in the roof of the nasopharynx,
bilateral lymphoid bands, the palatine tonsils, and the tonsil at the base of
the tongue (the lingual tonsil). The NALT is the main target site for vaccine antigens
in humans [193, 194, 197, 200, 201] . As the mucosal immune system develops, the
NALT is involved in a variety of important functions in relation to the host defense
mechanism, from being an impediment to drug absorption, serving as a guard
against attacking pathogens and antigens, facilitating the uptake of antigens, eliciting
the secretory antibody response, and inducing the immune response in the other
distant mucosal surfaces due to the function of the common mucosal immune
system. Owing to mucosal tolerance, it is also involved in preventing serious allergic
responses to inhaled antigens [194, 201, 202] .
On administration, the antigen interacts fi rst with the inductive tissue of the
MALT, thus initiating a primary response. The IgA serum cells are found in the
effector sites of the MALT, and local immunity results from the production of
the secretory IgA (s - IgA) response. As mentioned earlier, the NALT and the tonsils
form the main inductive sites in rodents and humans. These are composed of M cells
involved in the uptake of antigen and its presentation to the underlying lymphoid
tissues, the antigen being taken up by the M cells and the APCs, consisting of dendritic
cells, macrophages, and B cells; all these cells together with the T cells produce
the cellular and humoral immune responses [194] .
Vaccination by the nasal route produces a mucosal protection using mucus, the
epithelial surface, and both innate and acquired immune responses. The innate
defense mechanism plays a very important role in that it infl uences the type of
acquired immune mechanism, which mainly responds on the basis of “ immune
memory. ” The ability to attain these responses is the main principle of attaining
protection from infection.
5.6.9.3 Need for Adjuvants
As mentioned earlier, the subunit vaccines in particular require the use of adjuvants
in order to initiate an immune response leading to protection. The subunit vaccines