Mucosal immunogenicity

LAVELLE E 0, GRANT G, PUSZTAI A, PFULLER u, o hagan d t (2000) Mucosal immunogenicity of plant lectins in mice. Immunology. 99 30-37. 

E. coli 0157 H7 Intimin epitope Tobacco callus Mucosally immunogenic in mice when primed parenterally and boosted orally. Mice immunized parenterally and orally boosted showed reduced duration of colonization upon challenge. 92... 

Takahashi I, Marinaro M, Kiyono H et al. Mechanisms for mucosal immunogenicity and adjuvancy of Escherichia coli labile enterotoxin. J Infect Dis 1996 173(3) 627-635. 

Respiratory syncytial virus fusion protein Tomato fruit Mice developed serum and mucosal RSV-F- -specific antibodies. Immunogenic in mice when delivered orally. 31... 

In addition to the pivotal studies, several publications (Table 6.2) used other methods to test the response of individuals with celiac disease who were introduced to oats. These studies did not fulfill the selection criteria of pivotal studies namely an in vivo oats challenge with an intestinal/skin biopsy to assess the biological response to the introduction of oats into an otherwise gluten-free diet. Instead, they used various in vitro techniques to assess the immune response to avenin, or serology without an intestinal mucosal biopsy. Most of the methods used duodenal mucosal cultures prepared from biopsies or intestinal T cell lines obtained from individuals with celiac disease. Other studies measured the immunogenic reaction in peripheral lymphocytes or measured the presence of various antibodies in individuals with verified celiac disease who included oats in their diet, in comparison with a reference group (Table 6.2). Some of these studies used patients that were previously included in pivotal studies. These studies are identified with an asterisk ( ) in Table 6.2. 

In a more recent study, Webster et al. (2006) report the expression and characterization of lettuce-derived measles vaccine. The MV-H protein expressed in lettuce was demonstrated to be immunogenic in mice following intraperitoneal injection in the absence of adjuvant in addition to intranasal inoculation in the presence of a mucosal adjuvant. The highest response was observed in mice primed first with MV-H DNA and then boosted with an oral formulation of freeze-dried MV-H lettuce in conjunction with a mucosal adjuvant. In addition to this, the type of immune response was found to depend largely on the manner in which MV-H is presented to the immune system. Secreted and soluble forms of MV-H were demonstrated to induce a Th2 type response, while membrane-bound MV-H protein was found to be associated with a Thl response. 

The provocation of mucosal immunity against a given antigen can be achieved by other means besides oral ingestion. For example, intranasal administration of vaccine proteins can improve local mucosal immunity and enable large populations to be immunized at a lower cost. Plant-derived vaccines provide hope for more immunogenic, more effective and... 

A wide variety of novel approaches for the development of mucosal immune responses by administration of antigens in different delivery systems have been investigated, in many cases, with considerable success. These approaches include (1) the coadministration of immunogens with adjuvants active at the mucosal surface, (2) the coupling of immunogens to carrier molecules that promote their uptake at the mucosal inductive site, and (3) the expression of antigens in live attenuated bacterial or viral vectors, which can promote the colonization of mucosal tissue and the incorporation of antigens into a variety of microparticulate and adhesive vehicles, which are taken up in mucosal inductive sites. 

Seth A, Yasutomi Y, Jacoby H, Callery JC, Kaminsky SM, Koff WC, Nixon DF, Letvin NL (2000) Evaluation of a lipopeptide immunogen as a therapeutic in HIV type 1-seropositive individuals. AIDS Res Hum Retroviruses 16(4) 337-343 Shahin RD, Amsbaugh DF, Leef MF (1992) Mucosal immunization with filamentous hemagglutinin protects against Bordetella pertussis respiratory infection. Infect Immun 60(4) 1482-1488... 

The route of administration influences the likelihood of an antibody response independent of the mechanism of induction. The probability of an immune response is the highest with subcutaneous administration, less probable after intramuscular administration and intravenous administration is the least immunogenic route. There are no studies comparing parenteral and nonparenteral routes of administration. Flowever, as both mucosal tissues and the skin are immune competent organs designed to keep invaders out of the body, intranasal, pulmonary, and transdermal administration of therapeutic proteins may increase the risk of an immune response as compared to parenteral routes. 

Gluck R, Mischler R, Durrer P, Furer E, Lang AB, Herzog C, Cryz SJ Jr. Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant J Infect Dis 2000 181(3) 1129-32. 

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