Puig, Arturo; (2001) Lipopeptide vaccines against foot and mouth disease. Doctoral thesis (Ph.D.), University College London.

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Abstract

Vaccines are the most effective weapon against infectious diseases known to man. For over two centuries they have been successfully used for the protection of humans and domestic animals, and have been of great importance for the eradication of several pathogens. However, traditional vaccines present many problems such as their lack of stability, which requires the need for refrigerated transport and storage, and their limited safety, which requires the need of special containment units for handling them, in order to avoid serious outbreaks. An alternative to the use of classical vaccines is the development of synthetic vaccines. Synthetic vaccines contain only subunits of the pathogen, such as peptides taken from surface proteins, and since they contain no whole pathogen, they present no such risks and do not require special transport, handling or storage conditions. The formulation of a successful vaccine must include the sequence of the pathogen which we want the immune system to target (antigen), as well as an adjuvant that will enhance this immune response. If the antigen is of a low molecular weight, it must be coupled to a carrier to ensure that it is recognised by the immune system. In a fully synthetic vaccine, all three units: adjuvant, carrier and antigen, are linked covalently in one molecular unit. The objective of this thesis is to design and synthesize a fully synthetic vaccine against FMDV (Foot and mouth disease virus). Our candidate as a fully synthetic vaccine for FMDV uses a lipidic amino acid chain as a synthetic adjuvant, a polylysine matrix as a carrier (Multiple Antigen Peptide – MAP), and a sequence of the FMD viral surface protein corresponding to residues 139 to 155 of the sterotype O1-BFS as an antigen. This thesis describes an introduction to the mechanisms of the immune system, as well as a general introduction to vaccines, focusing on vaccines against FMDV. The chemical synthesis and characterisation of the compounds produced are included, and finally the immunological tests are described and the results interpreted.

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