Immunostimulating properties of a fragment of tgf-beta

#The present invention relates to immunogenic compositions comprising at least one fragment of TGF-β capable of eliciting an immunostimulating effect in an individual, and at least one immunogenic determinant against which it is desirable to elicit an immunogenic response.

#Transforming growth factor-beta (TGF-β) is a 25 kd dimer polypeptide that acts as a multifunctional cytokine in the regulation of a wide variety of cellular functions including cell growth and differentiation. TGF-β is secreted by virtually all cell types in an inactive form. This latent form can be activated by proteotytic cleavage of mature TGF-β from its precursor (at the Arg-Ala bond in position 278).

#Three forms, of TGF-β, TGF-β1, TGF-β2, and TGF-β3 have been identified in mammals, and methods for purifying TGF-β from various species such as human, mouse, green monkey, pig, bovine, and chick, and from various body sources such as bone, platelets, or placenta, are known. Methods for producing TGF-β in recombinant cell culture and for determining its activity have also been described (U.S. Pat. No. 5,061,786, and references incorporated therein).

#FIG. 1 illustrates the enhancing effect of TGF-29 on the immune response of 3 rabbits (#1-3) after experimental immunisation with the low immunogenic peptide “parv”. The immune response is indicated as the difference in ELISA reader measured milli absorbance between an immune serum after immunisation and the corresponding T0 serum before immunisation at each serial two-fold sera dilution.

#Figure illustrates the immune response of 2 rabbits (#264 and #265) over time after experimental immunisation with a TGF29-Parvo virus peptide conjugate. A) ELISA plates wherein TGF29 or “parv” were used as targets. Dark colour indicates a high antibody titer against the target in the serum sample B) The immune response is indicated as the difference in ELISA reader measured milli absorbance between an immune serum (T1, T2, T3 or T4) after immunisation and the corresponding T0 serum before immunisation, at three different 5-fold sera dilution (starting at 20% anti sera(as)), The immunesera T0-T5 were obtained as bi-weekly bleedings.

#FIG. 3 illustrates the dose response effect of TGF-29 on the immune response of rabbits (#242, #243, #244 and #24) to the immusied with a constant dosis of the parvo virus peptide “parv” together with Titermax adjuvant. The immune response is shown as difference in ELISA reader measured milli absorbance between an immune serum 3) after immunisation and the corresponding T0 serum before immunisation, at 3 serial five-fold antisera dilution (starting at 20% antisera (as) dilution). The T3 immunewera were collected 6 weeks after the first immunisation.

#Definitions

#Adjuvant: Any substance whose admixture with an administered immunogenic determinant increases or otherwise modifies the immune response to said determinant.

#Amino acid: Any synthetic or naturally occurring amino carboxylic acid, including any amino acid occurring in peptides and polypeptides including proteins and enzymes synthesized in vivo.