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

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 cell ular and Immoral immune responses when conjugated to KLH and adsorbed to al um. However, the free HGP-30 peptide is not immunogenic in animals. In orde r 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, resi dues 38-50, of the MHC I accessory molecule, human beta -2-microglobulin (b eta -2-M), referred to as Peptide J, or a peptide from the MHC II beta chai n (peptide G) were evaluated in mice. The effects of carriers and adjuvants on serum antibody titers, specificities to various HIV-1 clade peptides si milar to HGP-30 and isotype patterns were examined. Peptides J or especiall y G conjugated to modified-HGP-30 (LEAPS 102 and LEAPS 101, respectively) g enerated 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 patter ns indicative of a TH1 pathway (i.e. increased amounts of IgG2a and IgG2b a ntibodies). The ISA 51 and MPL (R) -SE adjuvants induced higher antibody re sponses than alum, with the ISA 51 being more potent. Immune responses to L EAPS 102, as compared to LEAPS 101, were weaker and slower to develop as de termined by antibody titers and cross clade reactivity of the antibodies in duced. Compared to KLH conjugates which induced significant anti-KLH antibo dy titers, minimal antibody responses were observed to peptide G, the more immunogenic conjugate, and peptide J. These results suggest that modified H GP-30 L.E.A.P.S. constructs may be useful as HIV vaccine candidates for pre ferential induction of TH1 directed cell mediated immune responses. (C) 200 1 Elsevier Science Ltd. All rights reserved.