IMMUNOCONJUGATES THAT WILL BE EFFECTIVE IN ELICITING ANTI-HIV RESPONSE

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An early manifestation of infection with HIV-1 is the loss of helper T (CD4+) cell function. Subsequently these cells are also depleted in number due to cytopathic effects of HIV-1. Since CD4+ T cells are required in antibody responses to protein antigens, deficiency in function or number of these cells would be expected to result in impaired antibody responses against HIV-1. Our approach for developing a vaccine to boost immune responses in HIV-1 infected individuals has been to use T-cell independent (TI) antigens and thus bypass the requirement for CD4+ T cells. It is known that Brucella abortus (BA) can be used as a carrier for haptens to stimulate antibody responses in the absence of T cells. Previously we showed that HIV-1 conjugated to Brucella abortus (BA) elicited anti-HIV antibody responses even in mice depleted odd CD4+ T cells. Since lipopolysaccharide (LPS) from other gram negative bacilli can stimulate B cells, we decided to purify LPS from BA in order to replace BA as the carrier. This will refine the use of BA as a carrier to molecule of defined structure and eliminate other BA elements that may be toxic. LPS from BA was purified and tested for functional activity. The hapten, trinitrophenyl (TNP) was conjugated to this LPS. TNP-LPS(BA) behaved as a T-independent type 1 carrier since anti-TNP responses were elicited in (i) nude mice that do not respond to T-dependent antigens and in (ii) CBA/n mice that do not respond to T- independent type 2 antigens (polysaccharides). TNP-conjugated forms of LPS from E. Coli and B. abortus were compared in C3H/HEJ mice, which have deficient macrophage responses to LPS. TNP-LPS (BA) induced anti- TNP belonging to all four IgG isotypes. This suggests that LPS from BA, unlike LPS from EC, can stimulate release of witch factors from T cells without requiring release of IL-1 from macrophages.