Routes of antigen administration

There are two general routes of antigen administration - parenteral and mucosal. The former refers to routes which involve penetration of the skin; the latter refers to absorption of antigen through a mucosal layer.

Parenteral administration

A number of routes are used in experimental work, including intradermal (i.d.), subcutaneous (s.c.), intramuscular (i.m.), intraperitoneal (i.p.) and intravenous (i.v.) administration. Three routes are mainly used in human administration. The smallpox (vaccinia) vaccine was routinely given by skin scari fication. Most vaccines given parenterally are by s.c. or i.m. administration, the choice largely depending upon the need for an alum adjuvant, when i.m. is the route of choice.

The last decade has seen a range of new preparations which, though not yet licensed as vaccines, hold considerable promise. DNA in the form of a plasmid is injected i.m. and this results in a long-lived immune response (antibody and cytotoxic T lymphocyte (CTL) formation). Rather large amounts are given (100 //,g) by this route, but much smaller amounts (<1 /ig) if adsorbed to tiny gold beads and delivered by a 'gene gun' into the mouse skin, can also give a good response. In the latter situation, examination has shown that some of the particles are taken up by Langerhans cells and carried off to the draining lymph nodes.

Mucosal administration

The area of mucosal surface available for infection by infectious agents and for antigen presentation is far greater than the skin area. Correspondingly, the mucosal surface is very well endowed with lymphoid tissue, in the gut by intraepithelial lymphocytes and Peyer's patches. The gut-associated lymphoid tissue (GALT) has been characterized in more detail than other sites. The major routes available for administration are oral, intranasal, ocular, intrarectal and vaginal (Table 1). These are anatomically discrete lymphoid compartments but there is a link between them which is referred to as 'the common mucosal system', whereby immunocytes sensitized at one site, particularly GALT, may transfer immunity after traveling to other mucosal and glandular sites.

Because of this relationship and the ease of administration, it is surprising that the oral route of administration of vaccines has not been more widely used other than for those vaccines which protect against diseases caused by agents, such as certain viruses and bacteria, which normally infect by this route. One reason is the need to avoid positive immune responses in the gut to food antigens, so that suppressor mechanisms are often activated. Second, for many antigens, much higher doses are required to achieve a desired response after oral compared to parenteral administration. Third, feeding an antigen orally does not necessarily result in a good immune response at all other mucosal sites. For example, there are only a few examples where oral administration of an antigen formulation has resulted in protection against a vaginal challenge.

Oral administration of live agent vaccines is effective for the prevention of enteric infections, such as poliomyelitis and typhoid fever and would be used for rotavirus and cholera vaccines. The adenovirus

Table 1 Mucosal routes of administration for current and some future vaccines

Route

Organisms

Oral"

Poliovirus (OPV), rotavirus, Salmonella,

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