title: Induction of cross clade reactive specific antibodies in mice by conjugates of HGP-30 (peptide analog of HIV-1(SF2) p17) and peptide segments of human beta-2-microglobulin or MHC II beta chain.
abstract: HGP-30, a 30 amino acid synthetic peptide homologous to a conserved region of HIV-1(SF2) p17 (aa86-115), has previously been shown to elicit both cellular and humoral immune responses when conjugated to KLH and adsorbed to alum. However, the free HGP-30 peptide is not immunogenic in animals. In order to improve the immunogenicity of HGP-30, peptide conjugates consisting of a modified HGP-30 sequence (m-HGP-30/aa82-111) and a peptide segment, residues 38-50, of the MHC I accessory molecule, human beta-2-microglobulin (beta-2-M), referred to as Peptide J, or a peptide from the MHC II beta chain (peptide G) were evaluated in mice. The effects of carriers and adjuvants on serum antibody titers, specificities to various HIV-1 clade peptides similar to HGP-30 and isotype patterns were examined. Peptides J or especially G conjugated to modified-HGP-30 (LEAPS 102 and LEAPS 101, respectively) generated comparable or better immune responses to modified HGP-30 than KLH conjugates as judged by the induction of: (1) similar antibody titers; (2) broader HIV clade antigen binding; and (3) antibody isotype response patterns indicative of a TH1 pathway (i.e. increased amounts of IgG2a and IgG2b antibodies). The ISA 51 and MPL(R)-SE adjuvants induced higher antibody responses than alum, with the ISA 51 being more potent. Immune responses to LEAPS 102, as compared to LEAPS 101, were weaker and slower to develop as determined by antibody titers and cross clade reactivity of the antibodies induced. Compared to KLH conjugates which induced significant anti-KLH antibody titers, minimal antibody responses were observed to peptide G, the more immunogenic conjugate, and peptide J. These results suggest that modified HGP-30 L.E.A.P.S. constructs may be useful as HIV vaccine candidates for preferential induction of TH1 directed cell mediated immune responses.
authors.affiliation: CEL-SCI Corporation, 8229 Boone Blvd, Suite 802, Vienna, VA 22182, USA. dzimmerman@cel-sci.com
authors.forename: D H
authors.initials: DH
authors.lastname: Zimmerman
authors.forename: J P
authors.initials: JP
authors.lastname: Lloyd
authors.forename: D
authors.initials: D
authors.lastname: Heisey
authors.forename: M D
authors.initials: MD
authors.lastname: Winship
authors.forename: M
authors.initials: M
authors.lastname: Siwek
authors.forename: E
authors.initials: E
authors.lastname: Talor
authors.forename: P S
authors.initials: PS
authors.lastname: Sarin
mesh_terms: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D006681:HLA-D Antigens / Q000737:chemistry / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013045:Species Specificity; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000939:Epitopes; D006183:H-2 Antigens; C052407:HGP-30 peptide, Human immunodeficiency virus-1; D015488:HIV Antigens; D006681:HLA-D Antigens; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D010455:Peptides; D001613:beta 2-Microglobulin; D054301:gag Gene Products, Human Immunodeficiency Virus; C041524:aluminum sulfate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin