Vaccines, nasal administration

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

Since the uptake of particles in nasal epithelial tissue is known to be mostly mediated by M cells, nasal administration has been investigated as a noninva-sive delivery of vaccines [37], However, since the uptake of naked DNA by endocytocis is limited, use of either nanoparticles as mucosal delivery systems [37] or hypotonic shock [38] is reported for the efficient transfection of gene and vaccine into the nasal epithelium. It was also reported that polypeptides and polypeptide-coated nanospheres (diameter about 500 nm) are transported through endocytic process in rat M cells [39],... 

Jabbal-Gill, I., Fisher, A. N., Rappuoli, R., Davis, S. S., and Ilium, L. (1998), Stimulation of mucosal and systemic antibody responses against Bordetella pertussis filamentous haemagglutinin and recombinant pertussis toxin after nasal administration with chitosan in mice, Vaccine, 16,2039-2046. 

Aramaki, Y., Fujii, Y., Yachi, K., Kikuchi, H., and Tsuchiya, S. (1994), Activation of systemic and mucosal immune response following nasal administration of liposomes, Vaccine, 12,1241-1245. 

Tarkowski A, Sun JB, Holmdahl R et ak Treatment of experimental autoimmune arthritis by nasal administration of a Type II collagen-cholera toxoid conjugate vaccine. Arthritis Rheum 1999 42(8) 1628-1634. 

Oral and Nasal DT associated to chitosan microparticles results in protective systemic and local inunune response against DT after oral vaccination, and in significant enhancement of IgG production after nasal administration... 

Other derivatives and chitosan salts, such as chitosan lactate, chitosan aspartate, chitosan glutamate, and chitosan hydrochloride, were also shown to be good candidates for nasal sustained release of, for example, the antibiotic vancomycin hydrochloride [87]. In addition, chitosan microparticles with diphtheria toxoid (DT) for nasal administration were produced. These microparticles administration resulted in a protective systemic and local immune response against DT with enhanced IgG production. The induction of serum IgG responses were similar to secretory IgA levels, and are superior to parenteral administration of the vaccine [88]. 

The ability to assemble self-adjuvanting immunogens obviates the need for emulsification in traditional and often harmful oil based adjuvants and also allows different delivery routes to be accessed. The PamSCys peptide was equally effective when delivered by the intranasal route as when delivered parenterally (Fig.6). Furthermore, the PamSCys-peptide elicited IgA antibody forming cells in the lung and draining lymph nodes following intra-nasal administration. Clearly the ability to induce IgA has ramifications for vaccines that are required to induce mucosal immune responses such as those to prevent respiratory diseases as well as HIV and other sexually transmitted pathogens. The ability to deliver vaccines... 

The nasal route is generating increasing interest as a route for the administration of local treatments and a cost-effective and patient-friendly alternative to injection for systemic delivery [49]. The special advantages of nasal delivery make it attractive for (i) crisis treatment where rapid onset of action is desirable (e.g., pain, migraine, panic attacks), (ii) systemic delivery of compounds that at present can only be delivered by injection (peptides/pro-proteins/vaccination), and (iii) direct targeting of the CNS (polar drugs for the treatment of CNS disorders). 

The nasal delivery of vaccines is a very attractive route of administration in terms of efficacy and consumer friendliness. A population-wide immunization against influenza has yet to be achieved. The pain of injections discourages many people from receiving a flu shot. The nasal route offers the advantage of a mucosal response followed by a seric response, and has proved to be a very efficient mode of administration. ... 

The live attenuated influenza vaccine is administered intra-nasally. A specially designed sprayer is inserted just inside the nostril, and the dose is squirted by depressing the plunger of the sprayer. The clip is removed from the plunger so that the second half of the dose can be administered into the other nostril. The vaccinated individual should breathe normally. There is no need to repeat the dose if the individual sneezes during or shortly after administration. ... 

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