title: Modification of delivery system enhances MHC nonrestricted immunogenicity of V3 loop region of HIV-1 gp120.
abstract: A successful peptide vaccine for AIDS is desired to elicit T-helper and cytotoxic T lymphocyte responses besides neutralizing antibodies. The V3 loop peptide of HIV-1 has been shown to contain the principal neutralizing domain, one of the most immunodominant regions, having both B-cell and T-cell determinants. In this study, the tip of the V3 loop region was mutated from GPGR to GPGQ based on the sequence of Indian isolates (CKRKIHIGPGQAFYT). To further enhance the immunogenicity of this epitope, two delivery systems of immune stimulating complexes (ISCOMs) and liposomes were used to incorporate the peptide. Mice of differing haplotypes, H-2b, H-2d, H-2k and H-2s, showed no MHC restriction when immunized with these formulations. The IgG levels as assessed by ELISA were found to be significantly higher (P < 0.05 to P < 0.001) for even five-fold lower doses of the peptide in ISCOMs and liposomes as compared to the conventional alum-based preparation. The major subtype elicited was IgG2a/IgG2b, suggestive of a Th1-like response for all the formulations. Thus, it would appear that the same peptide incorporated in ISCOMs and liposomes selects a Th1 response and may therefore be important not only for neutralization but also for virus clearance.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, New Delhi.
authors.forename: A
authors.initials: A
authors.lastname: Ahluwalia
authors.forename: K
authors.initials: K
authors.lastname: Gokulan
authors.forename: I
authors.initials: I
authors.lastname: Nath
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D016882:ISCOMs / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D006183:H-2 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D016882:ISCOMs; D007074:Immunoglobulin G; D008081:Liposomes; D010446:Peptide Fragments