Award details

Formulation and development of peptide based oral vaccines.

Reference	BB/G017948/1
Principal Investigator / Supervisor	Professor Yvonne Perrie
Co-Investigators / Co-Supervisors	Dr David Anderson
Institution	Aston University
Department	Sch of Life and Health Sciences
Funding type	Skills
Value (£)	74,410
Status	Completed
Type	Training Grants
Start date	01/10/2009
End date	30/09/2013
Duration	48 months

Abstract

unavailable

Summary

Vaccination of the population offers tremendous benefit to both human and animal health. Immunisation against infections is a more efficient and effective alternative to chemotherapy, with the widespread use of vaccines preventing millions of deaths each year. The route of administration of a vaccine has a significant impact on large scale vaccine programmes, with the oral route offering convenient, cost-effective vaccination without the need for injections. This avoids problems of needle-stick injuries, the large-scale disposal of bio-hazard needles and the necessity for trained personnel. However vaccines, being inherently labile biologicals are rapidly degraded in stomach and require a delivery system to provide protection and enhance delivery to appropriate tissues to stimulate an effective immune response. The Industrial partner has proprietary technology that analyzes viral sequences isolated from infected individuals to identify regions of the virus that are most vulnerable to immune-based therapies. Using this technology, a selection of peptides have been designed to protect against several strains of influenza and produce broadly reactive immune responses. Within this project VBI will apply this technology to identify peptides which offer protection against further strains of influenza and also possible immunisation against HIV and West Nile Virus. The application of bioinformatics to design synthetic peptides differs from all past and current vaccine strategies offered by other vaccine producers. The academic partner will be responsible for the formulation and application of colloidal drug delivery systems to enhance the potency of these peptides by offering protection from degradation and enhancing delivery to the appropriate immunological site. Lipid vesicles incorporating bile salts (bilosomes), which can entrap peptide antigens, will be used for the oral delivery of the peptide antigens. The ability of these bilosomes to withstand disruption within the gastro-intestinal fluid, and remain stable means they are able to protect the peptide antigen. To enhance their efficacy, the bilosome formulation will be systematically investigated; factors which control the bilosome characteristics will be identified by varying each of the bilosome components and rigorously analysing them. Bilosomes will then be optimised to incorporate and carry high peptide payloads, display stability both on storage and in the presence of gastrointestinal biological milieu, and deliver the vaccine to the appropriate lymphatic tissue. Formulation of these systems as a liquid dosage form also imposes several limitations: generally these formulations require cold-chain distribution to limit instabilities including chemical and physical (aggregation, precipitation, loss of antigen) changes which can inhibit their potency. To circumvent this problem lyophilisation will be applied to produce a stabilised dry dosage form. The use of lyoprotectants, including carbohydrates, will be investigated to stabilise the bilosomes and protect the peptide during the drying process. The aim of this proposal is to produce an effective synthetic oral vaccine against influenza formulated as a dried product. The vaccine will comprise of an immunogenic peptide and a drug delivery system. Key objectives in achieving this will be; 1. To determine the physicochemical characteristics and compositions of bilosome vaccine delivery system which promote peptide antigen loading and retention and correlate this with their immunological activity. This will help VBI identify a lead vaccine formulation for pre-clinical trials. 2. To understand and use these relationships so as to design effective oral vaccine delivery systems in a dry dosage form. This will support the translation of research systems into new pharmaceutical products. 3. To provide training of a graduate researcher with key transferable skills and expertise in an under resourced research area.

Committee	Not funded via Committee
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	Training Grant - Industrial Case

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