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ANTIGEN DELIVERY SYSTEMS13

To dramatize the importance of mucosal antigen delivery systems, three important concepts bear repeating:

  1. Most infectious diseases or agents enter through the mucosal tissues. In terms of incidence and burden, this includes a billion cases of diarrhea at any given time. Bacteria such as salmonella, Shigella, vibrio, etc., spread at roughly one-half million cases per hour, just among children, 500 of whom will die. Viruses such as hemophilus, pneumococcus, and measles infect some 14,000 case per hour. AIDS infects 340 people per hour, 80 percent of 90 percent of them through a mucosal surface.

  2. The entire immune system is stimulated by what we eat and by what compromises our mucosal surfaces. There are roughly 1014 bacteria living in the human gut. Each person ingests about one metric ton of solids and liquids per year. About 10 milligrams of undigested protein are “injected” into the circulation every day. Some 70 percent of all lymphoid cells are associated with mucosal tissues, and the gut has more macrophages than the liver.

  3. There is a common immune system. The concept of systemic immunization, first recognized by Erlich in 1891, involves the stimulation of cells from inductive sites (e.g., Peyer’s patches in the intestine) to remote sites (e.g., nasal passages, salivary glands, even the genital tract). In both monkeys and mice, for example, intranasal immunization produces a greater antibody response in the genital tract than any other route. The instrument of this response is the M-cell, which can internalize both particulate and soluble antigens.

Research on Antigen Delivery Systems. The central problem with mucosal application of antigens is the small quantity of antigen that is absorbed, due to degradation by enzymes, mucous coatings, etc. Typical absorption rates for proteins are only 1:100,000. Taking antigen with food can reduce degradation somewhat, as can encapsulation—protecting the antigen from the stomach in order to deliver it to a desired segment of the intestine.

A few groups in Europe and the United States are using liposomes to deliver antigens. In the mouth, this can reduce the formation of plaque and the incidence of dental caries. However, liposomes are relatively unstable in the internal environment. Others are working with mucosal adhesives, microspheres, CT and CPB conjugates, and live pathogen delivery systems.

The goal of this research could be called the “dream vaccine” —something safe and stable that might be produced locally, could be administered orally in one dose to provide both systemic and mucosal immunity, possibly to several

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Based on a presentation by Jeri Mestecky, M.D.



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