Oral vaccination mucosal adjuvants

Holmgren, J., N. Lycke, C. Czerkinsky, Cholera-Toxin and Cholera-B Subunit as Oral Mucosal Adjuvant and Antigen Vector Systems, Vaccine. 11, 1179, 1993. 

This chapter first provides a description of immunity in general and then more specifically, immunity in the mucosal immune system. The immune response of both intestinal and respiratory tracts will be described in detail as these are the two most common portals of targeted vaccine development for mucosal immunity. The chapter will cover the basis of mucosal immunity using plant-based oral vaccines. Strategies for increasing mucosal immunity, such as the use of adjuvants, will also be discussed. Finally, the chapter will cover the precliiucal tests and various cliiucal trials that are taking place with respect to production of human and veterinary therapeutic proteins in plants. 

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 most potent mucosal adjuvants have been shown to be the toxins derived from Vibrio cholerae or Escherichia coli, which should not be surprising since these organisms invade the body through the GI tract. Obviously too toxic for human use because they are the source of cholera or diarrhoea, heat labile enterotoxins have been tested in mice and shown to be potent adjuvants for orally or nasally administered influenza vaccine. The potency of heat-labile enterotoxin mutants may also be enhanced by formulation into bioadhesive particulate delivery systems, and this is an area under current exploration. 

Mucosal adjuvant and vaccine delivery system development is an area of importance for improving public health. Mucosal immunization can serve in the future in increasing mucosal immune function, induction of protective immunity against infections, and induction of tolerance or modifying autoimmune disorders, allergies, and autoimmune diseases. Development of oral vaccines would have large implications for rural and remote populations where access to trained medical staff to administer vaccines by injection can be lacking. 

The mucosal vaccines approved for human use include typhoid, cholera, adenovirus, Sabin oral polio, and rotavirus vaccines. New mucosal vaccine strategies are focused on development of non-replicating subunit vaccines, DNA, plant, and other types of recombinant vaccines as well as the use of mucosal adjuvants preferably inbuilt into the vaccine. The conjugation of lipids to peptide antigens is one approach which enables the production of highly... 

Zhang X, Zhang X, Yang Q (2007) Effect of compound mucosal immune adjuvant on mucosal and systemic immune responses in chicken orally vaccinated with attenuated Newcastle-disease vaccine. Vaccine 25(17) 3254-3262... 

Homquist, E. Lycke, N. Czerkinsky, C. Holmgren, J. Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen carrier systems. In Novel Delivery Systems for Oral Vaccines O Hagan, D.T., Ed. CRC Press, Inc. Ann Arbor, MI, 1994 157-173. 

In recent years, the use of biomaterial as vaccine adjuvants has received considerable interest in oral and parenteral vaccine development. They have been formulated to elicit either mucosal or humoral immxmity via targeted phagocytosis in the Peyer s patches or as conventional subcutaneous depots. Golembek et al. were one of the first groups to apply microspheres for tumor immxmotherapy. GM-CSF or IFN-y was encapsulated in gelatin-chondroitin sulfate microspheres and mixed with irradiated B16/F10... 

Another limitation of traditional adjuvants is the limited routes of administration, and to this end, efforts have been made to prepare polyphosphazene adjuvant formulations for mucosal delivery [25]. In recent work it was shown that PCEP combined with the influenza vaccine X 31 could be applied successfully via intranasal, oral and intrarectal routes [48], with intranasal application proving to be superior to the other routes tested. Moreover, a cooperative effect with enhancement of Thl-cell-mediated and Th2 humoral responses was observed, meaning mucosal delivery of PCEP adjuvants may prove to be an optimal route for protection against influenza viruses as well as with other vaccines. 

Wang D, Kandimalla ER, Yu D et al (2005) Oral administration of secraid-genCTatiOTi immunomodulatory oligonucleotides induce mucosal Thlimmune responses and adjuvant activity. Vaccine 23 2614—2622... 

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