Adjuvants vaccination strategies

Current efforts in vaccine development have predominantly utilized clade B isolates, which represent the subtype in North America and Western Europe. There is also an increased interest in the development of clade A and C vaccines for the expanding pandemic in Asia and sub-Saharan Africa. A concern in fhe clade-specific vaccine strategy is the potential inability to produce large amounts of vaccine specific for distinct clades. This leaves open the question of specific vs. cross-clade effectiveness. Choice of immunogen(s), adjuvant, dose, and mode of administration are also additional variables that must be addressed in candidate vaccine research. 

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. 

Recently, there has been renewed interest in developing vaccines for use in cancer treatment. The main factors giving impetus to this therapeutic approach include a better understanding of the immune system, the identification of several T cell-specific tumor antigens, more effective adjuvants, and the ability to construct more immunogenic molecules using recombinant DNA techniques (Murray et al., 2000). Current vaccine strategies for the treatment of solid tumors tend to focus on the cellular arm of the immune response. 

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... 

Taking all of these results together, the use of poly-L-arginine as a cationic peptide delivery system, when combined with a second adjuvant such as CpG-ODN, may represent an improved vaccine strategy for humans in order to induce antigen-specific type 1 immune responses. 

P7-RANTES, another analog directly isolated from the initial RANTES/CCL5 library (Hartley et al., 2003), was encoded as an adjuvant in a DNA vaccine strategy and demonstrated to be capable of enhancing anti-tumor immune responses by increasing levels of local leukocyte recruitment (Dorgham et al., 2008). 

The development of vaccines based on S-layer technologies has focused on two strategies (1) exploiting S-layers present on pathogenic organisms, and (2) use of S-layer lattices as carrier/adjuvants for vaccination and immunotherapy [100,101]. 

Fries, L.F. et al., Liposomal Malaria Vaccine in Humans A Safe and Potent Adjuvant Strategy, Proceedings of the National Academy of Sciences of the United States of America. 89, 358, 1992. 

Brennan, F.R. and Dougan, G., Non-clinical safety evaluation of novel vaccines and adjuvants New products, new strategies, Vaccine, 23, 3210, 2005. 

Fries, L.F., Gordon, D.M., Richards, R.L., Egan, J.E., Hollingdale, M.R., Gross, M., Silverman, C., Alving, C.R. Liposomal malaria vaccine in humans a safe and potent adjuvant strategy. Proc Natl Acad Sci USA 89 (1992a) 358-362. 

The purpose of this chapter is to review and discuss the preclinical safety evaluation strategy for vaccine approaches to the prophylaxis and treatment of viral diseases. This chapter will discuss the newer approaches to vaccination and will include recombinant proteins, peptides, polysaccharides, DNA plasmids, and viral vectors with and without adjuvants. It is outside the scope of this chapter to discuss whole cells expressing immunogens, live attenuated viruses, bacteria, or parasites. 

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