Particular Type of Antigen-Fusion Polypeptides
Thermally Responsive Polymers Fused to Antigens
–Antigen-Carrier-Elastin-Like Peptide Fusion Peptides: Krebs (US13/990344) discloses fusion proteins of an immunogenic carrier protein containg a thermally-responsive aggregation (TRA) polypeptide to control protein aggregation. At lower temperatures the fusion protein is soluble and easy to purify whereas at higher temperature (aboe about 30C) the thermally responsive peptide moeity induces aggregation of the fusion protein which causes higher antigenicity. Examples include an antigen which is linked to a carrier protein (GroIL) containing a thermally-responsive aggregation polypeptide. The fusion proteins can also contain sequence tags for affinity purificaiton (such as His6 tags) or B and T cell activating sequences to enhance immune response.
Antigen-PolyQ domain fusion: Illyinski (Vaccine 26 (2008) 3223-3226) disclose stimulating aggregation of an antigenic protein by its fusion to polyQdomain enhanced its antigenic potention. Specifically, the weakly immunogenic model antigen GFP was fused to either long polyQ domain that triggered protein aggregation or short polyQ domain that did not promote aggregation. Fusion with the long polyQ domain fusion proteins strongly enhanced anti-GFP CTL activity compared with the smaller polyQ domain fusion.
Heat Shock Protein (Hsp) fusions:
Hsp fusion proteins elicit antigen specific CTL resposnes in the absence of adjuvants. Immunization of mice with a soluble fusion protein consisting of an ovalbumin fragment, a well charcterized T cell antigen, covalently linked to mycobacterial Hsp70 induced a strong MHC class I restricted CD8 T cell response. Today Hsps are the object of intense work as a potential means of vaccines to treat cancer and other diseases. Hsps as vaccines are a novel approach to disease prevention. Epitope analysis indicates the presence of multiple B and T cell epitopes in many of these Hsps. They can be used as carriers and vectors. Hsp based vaccines, unlike other recombinant protein based vaccines, stimulate both humoral and cell mediated immune respones. Sairam (US2010/0196416).
Krebs (US13/990344) teaches an antigen fused to a carrier protein such as GroEL fused at its 3′ end to a thermally responsive polypeptide such as an elastin like peptide.
Sairam (US2010/0196416) discloses a Hsp, in part or whole, either alone or covalently or non-covalently bound to an antigenic molecule, which when adminsitered elicits specific immunolgogical resposnes in a host. The Hsps are DnaK (Hsp70) or GroEL protein (Hsp60) of S. typhi eitehr alone or in combination with antigenic molecules, as a vaccine to augment the immune resposne against S. typhi in mice.