Development of optimized adjuvant vectors for DNA vaccination

• Applicant: Professor Dr. Jürgen Haas
• Subject Area: Virology
• Term: from 2000 to 2003
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5266546

Although DNA vaccines were recently shown to induce protective immunity against a variety of pathogens and although several vaccines are currently being tested in phase III studies in human, there are several lines of evidence indicating that results from small animal models can not readily be transfered to human. Thus, probably most DNA vaccines currently used in experimental animal systems will have to be considerably improved in order to be protective in human. We were recently able to show that the immunogenicity of DNA vaccines can be dramatically increased by codon optimization. The immunogenicity of DNA vaccines can also be modified by adjuvants und "adjuvant" plasmids coding for cytokines. For subunit and inactivated vaccines developed to induce mucosal immunity, V.cholerae choleratoxin (ctx) and E.coli heat-labile enterotoxin (LT) are well-known to be among the strongest adjuvants. However, both the prokaryotic toxin sequences as well as cytokine genes appear to be composed to a variable extent of codons only rarely used in human, similar to other bacterial proteins and mammalian regulatory proteins usually expressed in tiny amounts. The objective of this study is to develop adjuvant vectors for DNA vaccination which are based on codon-optimized, highly expressed sequences encoding ctx, interleukins and chemokines to improve both systemic, and, most importantly, mucosal immunity.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1089: Novel Vaccination Strategies