Vaccine approaches

It is not the focus of this chapter to discuss detailed mechanisms underlying vaccine protection. However, to appreciate the rationale and the strengths and weaknesses of different vaccination approaches, it is helpful to have a rudimentary understanding of the immune system and how it responds to infection and vaccination. 

Nevertheless, the inactivated vaccine approach suffers from several shortcomings. The process could inactivate not only the organism but also destroy the antigen conformation required to elicit protective immunity. Incomplete inactivation (e.g., virion aggregation resulting in poor exposure to the inactivating agent) could result in disease transmission or severe complica-... 

Both subunit and live, attenuated vaccine approaches are being developed for RSV. A candidate subunit vaccine based on the surface (F-) protein is being tested. Live attenuated vaccines for RSV are also being developed. 

Brayden DJ, Baird AW (2001) Microparticle vaccine approaches to stimulate mucosal immunisation. Microb Infect 3(10) 867-876 Brewer JM (2006) (How) do aluminium adjuvants work Immunol Lett 102(1) 10-15 Buwitt-Beckmann U, Heine H, Wiesmuller KH, Jung G, Brock R, Akira S, Ulmer AJ (2005) Toll-like receptor 6-independent signaling by diacylated lipopeptides. Eur J Immunol 35(1) 282-289... 

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. 

Live and vector vaccine approaches should take into account the epidemiological situation and health care schemes in the target countries. The efficacy of live vaccines and vectors may be affected by a pre-existing immunity in the population. Live vaccines can also interfere with screening tests, e.g. for salmonellosis in people who handle food or for bovine leukosis in eradication schemes. 

Huang DW, McKerracher L, Braun PE, David S (1999) A therapeutic vaccine approach to stimulate axon regeneration in the adnlt mammalian spinal cord. Neuron 24 639-647. 

With these novel vaccination regimens at hand, it must be evaluated whether cancer can efficiently be cured by a combined application of chemotherapy, radiation therapy, cellular vaccination and/or peptide- or protein-based vaccination. The application of immunotherapy of cancer may be envisaged for cancer patients who have undergone a chemo- or radiation therapy first to reduce the size of the tumor(s) to a minimum before vaccination. The continued identification of tumor-associated or tumor-specific peptides and proteins will enable peptide or protein vaccines to be applied to cancer patients. Those patients who suffer from cancers for which no tumor-derived antigens have been identified could, alternatively, be treated with cellular vaccines. The therapeutic vaccination approach with either vaccine type could hopefully prevent the recurrence of meta-stases and possibly help patients in the cure of this devastating disease. 

An additional route of uptake upon peroral administration is the passage of the M-cells of the Peyer s patches [18]. Although this route in essence has only a low transport capacity, it is of importance for mucosal (peroral) vaccination, for example. The Peyer s patches are located in the small intestine where M-cells, which neither possess a mucus nor a glycocalix layer in comparison to the adjacent enterocytes, allow the drug uptake via transcytosis. The drug is then transported into the lymphatic system and causes an immune response in the case of the vaccination approach. Absorption via M-cells in essence is possible due to the decreased enzymatic activity and their rather high permeability. 

Muller-Schiffmann A, Korth C (2008) Vaccine approaches to prevent and treat prion infection progress and challenges. BioDrugs 22 45-52... 

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