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(-CELL DEPLETION() T)

Human immunodeficiency virus type 1 (HIV-1) infection is associated wi th 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 stud y we coupled a 14-mer V3 loop peptide (V3), which is homologous to 9 o f 11 amino acids from the V3 loop of HIV-1 MN, and gp120 from HIV-1 SF 2 to B. abortus [gp120(SF2)-B, abortus]. Our results showed that speci fic 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 recom binant vaccinia virus gp160 vector (VPE16), Sera from mice immunized w ith gp120(SF2)-B, abortus inhibited binding of soluble CD4 to gp120, w hereas sera from mice immunized with V3-B, abortus were ineffective, S era 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 gp12 0(SF2)-B. abortus were more potent than sera from mice immunized with V3-B. abortus in inhibiting syncytia from heterologous HIV-1 laborator y strains, Importantly, in primary and secondary responses, V3-B. abor tus evoked anti-HN MN antibodies in mice depleted of CD4(+) cells, and sera from these mice were able to inhibit syncytia, These findings in dicate that B, abortus can provide carrier function for peptides and p roteins from HIV-1 and suggest that they could be used for immunizatio n of individuals with compromised CD4(+) T-cell function.