BRUCELLA-ABORTUS CONJUGATED WITH A GP120 OR V3 LOOP PEPTIDE DERIVED FROM HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 INDUCES NEUTRALIZING ANTI-HIV ANTIBODIES, AND THE V3 B-ABORTUS CONJUGATE IS EFFECTIVE EVEN AFTER CD4(+) T-CELL DEPLETION

Human immunodeficiency virus type 1 (HIV-1) infection is associated with loss of function and numbers of CD4(+) T-helper cells, In order to bypass the requirement for CD4(+) cells in antibody responses, we have utilized heat-inactivated Brucella abortus as a carrier, In this study we coupled a 14-mer V3 loop peptide (V3), which is homologous to 9 of 11 amino acids from the V3 loop of HIV-1 MN, and gp120 from HIV-1 SF2 to B. abortus [gp120(SF2)-B, abortus]. Our results showed that specific antibody responses, dominated by immunoglobulin G2a in BALB/c mice, were induced by these conjugates, Sera from the immunized mice bound native gp120 expressed on the surfaces of cells infected with a recombinant vaccinia virus gp160 vector (VPE16), Sera from mice immunized with gp120(SF2)-B, abortus inhibited binding of soluble CD4 to gp120, whereas sera from mice immunized with V3-B, abortus were ineffective, Sera from mice immunized with either conjugate were capable of blocking syncytium formation between CD4(+) CEM cells and H9 cells chronically infected dth the homologous virus, Sera from mice immunized with gp120(SF2)-B. abortus were more potent than sera from mice immunized with V3-B. abortus in inhibiting syncytia from heterologous HIV-1 laboratory strains, Importantly, in primary and secondary responses, V3-B. abortus evoked anti-HN MN antibodies in mice depleted of CD4(+) cells, and sera from these mice were able to inhibit syncytia, These findings indicate that B, abortus can provide carrier function for peptides and proteins from HIV-1 and suggest that they could be used for immunization of individuals with compromised CD4(+) T-cell function.