DERIVATIZATION WITH MONOMETHOXYPOLYETHYLENE GLYCOL OF IGS EXPRESSING VIRAL EPITOPES OBVIATES ADJUVANT REQUIREMENTS

Ig molecules expressing within the CDR3 loop viral B or T cell epitope s were derivatized with mPEG 5,000. Pegylated Ig were used to investig ate the in vitro and in vivo effect of pegylation on the immunogenicit y of viral epitopes expressed in chimeric Ig. Two chimeras were used i n this study: Ig-HA carrying a CD4 epitope corresponding to amino acid residues 110-120 of the hemagglutinin (HA) of PR8 influenza A virus a nd Ig-V3C, a murine-human chimera carrying a consensus B cell epitope from the V-3, loop of HIV-1 gp120 protein. Pegylated Ig-HA (Ig-HA-mPEG ) with 6 to 8% substituted lysine residues showed in vivo resistance t o enzymatic degradation and persisted significantly in blood circulati on and lymphoid organs. Moreover, Ig-HA-mPEG was able to activate in v itro HA110-120-specific hybridoma T cells and to prime T cell prolifer ative response in vivo without requirement for adjuvant. Also, mildly pegylated Ig-V3C (Ig-V3C-mPEG) administered into BALB/c mice in the ab sence of adjuvant induced specific Ab response to V3C peptide with ins ignificant response to xenogeneic human Ig determinants.