Adjuvants (see outline)

ProPred (graphical web tool for predicting MHC class I binding regions in antigenic protein sequences). 

Deisgn for binding to MHC Molecules:

It is well established that binding of a peptide to an MHC molecule is a prequisite for activtion of antigen specific T cells. As only certain peptides can bind to a given MHC molecule, the identificaiton of these peptides is one of the bottlenecks in subunit vaccine design. A number of methods have been developed to predict MHC binding peptides. (Sing “ProPred: prediction of HLA-DR binding sites) pp. 1236-1237, vol 17, no. 122001).  

Virus like particles (VLPs): 

Some viral proteins spontaneously assemble into highly repetitive virus like particles (VLPs) and induce strong B cell responses in the absence of adjuvants. Moreover, foreign epitopes inserted into such VLPs induce a similarly strong B cell response. However, the size and nature of epitopes that can be inserted into VLPs is restricted and VLPs containing peptides longer than 20 amino acids often fail to assemble. While peptides genetically fused to either the N or C terminus of VLPs present fewer assembly problems, the immune response obtained against such epitopes are often limited, most likely because the epitopes are not optimally exposed. In addition, such particles may be less stable in vivo.

Hepatits B core antigen (HBcAg) -VLP fusions: Jegerlehner shows that peptides and proteins engineered to contain a free cys can be chemcially coupled to VLPs formed from the hepatits B core antigen (HBcAg) containing a lys in the immuno-dominant region. These antigen-decorated VLPs induced potent and long lived immune responses even against self epitopes in the absence of adjuvants. (Jegerlehner, Vaccine 20 (2002) 3104-3112).

Rabbit haemorrhagic disease virus (RHDV): Peacey show that the capsid protein VP60 of RHDV which spontaneously forms VLP can be genetically modified with various short peptide sequences capable of being presented to and recognised by immune cells. A chemical linker was utilised to covalently conjugate both small peptides and whole protein to the RHDV VLP scaffold. The approach enabled surface conjugation of a substantial range of antigens without the constraints imposed by subunit folding and VLP formation. Attachment of antigen to RHDV VLP conferred the immuno stimulatory properites of the underlying viral shell to the conjugated antigen, and so enable the initiation of both antigen specific humoral and cell mediated immune resposnes.