Mucosal vaccination/immunization

The induction of an immune response by various mucosal routes is an important approach for the control of mucosally acquired infections. The apparent linked nature of the mucosal immune system enables the delivery of an antigen to any mucosal surface to have the secondary effect of potentially inducing immunity at others. Induction of a combination of systemic and secretory immune responses can be determined by the nature of the antigen, the route of administration, and the delivery system utilized. For example, traditional parenteral vaccines primarily induce IgM and IgG responses, whereas mucosal vaccination can elicit both IgG and secretory IgA responses (Corthesy, 2007). 

Walker, R.I. (1994). New strategies for using mucosal vaccination to achieve more effective immunization. Vaccine 12(5) 387—400. 

Nevertheless, there is also accumulating evidence that a certain regionalization exists in the mucosal immune system, in particular a dichotomy between the gut and the upper respiratory tract. Differences in the antigenic repertoire, adhesion molecules or chemokines involved in leukocyte extravasation might explain this disparity. Primed immune cells may tend to home to the effector sites corresponding to the inductive sites, where the initial antigen contact took place. Such regionalization within the common mucosal immune system has to be taken into account in the development of certain mucosal vaccines [11]. 

McLean, C.S., D. NiChallanain, I. Duncan, M.E.G. Boursnell, R. Jennings, and S.C. Inglis. 1996. Induction of a protective immune response by mucosal vaccination with a DISC HSV-1 vaccine. Vaccine 14 987. 

The lipid-core peptide (LCP) system (Toth et al. 1993 Moyle et al. 2003) (Fig. 11.3) is a delivery system which conjugates synthetic lipoamino acids (a-amino acids with long alkyl side chains) through a polylysine MAP system (or a carbohydrate) (McGeary et al. 2001, 2002) to multiple copies of one or several different peptide antigens. The LCP system induces similar immune responses when LCP-based vaccines are co-administered with conventional adjuvants and represents a promising system for mucosal vaccine development. 

Parenteral Route. Parenteral vaccination remains the immunization method of choice for most antigens because it provides more effective immune response than do any other routes of vaccination in most cases. Every years millions of people receive inactivated influenza vaccine by parenteral administration. Subcutaneous vaccination with inactivated influenza vaccine is known to induce simultaneous immune responses in the blood and upper respiratory tract of subjects. The immune response, i.e., the increase in the number of influenza virus-specific antibody-secreting cells in peripheral blood and tonsils, increased rapidly to reach a peak within 1 week after vaccination.Parenteral vaccination of a DNA vaccine encoding glycoprotein D of herpes simplex virus type 2 resulted in systemic cellular and humoral responses. The mucosal humoral responses generated by intramuscular and intradermal vaccination were comparable with those obtained by mucosal vaccination. The DNA vaccine was able to... 

Other selection criteria may be considered. The mini-pig is a good model for studying intracutaneous or topical vaccines.29 For a mucosal vaccine, Glueck30 used the baboon to investigate a novel adjuvant for intranasal immunization, based on the physiological and pharmacology similarity with man. However, other species should be considered first, and certainly rats, mice, and rabbits have been used. For further discussion, see safety evaluation of toxin adjuvants delivered intranasally by Lang.31... 

Recently, a vaccine made from the recombinant BoNT C fragment has been reported to protect nonhuman primates from an aerosol exposure of BoNT, and neutralizing antibody titers were detected for up to 2 years following vaccination (Boles et ah, 2006). In addition to needle delivery, there is a considerable interest in developing a mucosal vaccine for BoNT. This is based on the premise that the mucosal immune system would be the hrst line of defense for inhaled BoNT, and administration of mucosal vaccines may be easier to carry out in the general population (Park and Simpson, 2004 Fujihashi et ah, 2007). 

An area where biodegradable particulate drug carriers have been found promising is in the development of oral vaccines (242-258). Because most infectious species enter the body through mucosal surfaces, immunization involving these surfaces can be expected to be an... 

Bermudez-Humaran, L.G., Cortes-Perez, N.G., Lefevre, F., et al. (2005) A novel mucosal vaccine based on live lacto-cocd expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors. J Immunol 175, 7297-7302. 

The indications are that gut antigen-based vaccines, at least based on the antigens described above and mediated by high systemic antibody responses, are unlikely to be wholly effective against non-blood-feeding nematodes. Different antigens may be required and may need to be delivered in such a way as to stimulate local mucosal immune responses. 

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