Derivatization with monomethoxypolyethylene glycol of Igs expressing viral epitopes obviates adjuvant requirements.
Ig molecules expressing within the CDR3 loop viral B or T cell epitopes were derivatized with mPEG 5,000. Pegylated Ig were used to investigate the in vitro and in vivo effect of pegylation on the immunogenicity of viral epitopes expressed in chimeric Ig. Two chimeras were used in this study: Ig-HA carrying a CD4 epitope corresponding to amino acid residues 110-120 of the hemagglutinin (HA) of PR8 influenza A virus and Ig-V3C, a murine-human chimera carrying a consensus B cell epitope from the V3 loop of HIV-1 gp120 protein. Pegylated Ig-HA (Ig-HA-mPEG) with 6 to 8% substituted lysine residues showed in vivo resistance to enzymatic degradation and persisted significantly in blood circulation and lymphoid organs. Moreover, Ig-HA-mPEG was able to activate in vitro HA110-120-specific hybridoma T cells and to prime T cell proliferative response in vivo without requirement for adjuvant. Also, mildly pegylated Ig-V3C (Ig-V3C-mPEG) administered into BALB/c mice in the absence of adjuvant induced specific Ab response to V3C peptide with insignificant response to xenogeneic human Ig determinants.
Brumeanu
T D
TD
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
Zaghouani
H
H
Elahi
E
E
Daian
C
C
Bona
C A
CA
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D006389:Hemagglutinins, Viral / Q000276:immunology*; D007136:Immunoglobulins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols / Q000737:chemistry*; D011863:Radioimmunoassay; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014018:Tissue Distribution
D000276:Adjuvants, Immunologic; D006389:Hemagglutinins, Viral; D007136:Immunoglobulins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol