MONOPHOSPHORYL LIPID-A ENHANCES BOTH HUMORAL AND CELL-MEDIATED IMMUNE-RESPONSES TO DNA VACCINATION AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

To enhance immunity induced by DNA vaccination against human immunodef iciency virus type 1 (HIV-1), we evaluated the efficacy of monophospho ryl lipid A (MPL), an adjuvant of bacterial origin. BALB/c mice were I ntramuscularly injected with immunogenic DNA, encoding the env and rev genes of the HIV-1(IIIB) strain, formulated with MPL dissolved in dif ferent vehicles (MPL in stable emulsion and MPL in aqueous formulation ). The sera from mice immunized with the two preparations of MPL revea led 2(6) to 2(9) times higher HIV-1-specific immunoglobulin G (IgG) ti ters than the sera from mice immunized without MPL. In virus neutraliz ation tests for HIV-1(IIIB) by p24 assay and antifusion assay of infec ted MOLT-4 cells, MPL tends to elicit antibody more protective than an tibody elicited without adjuvant. MPL also elicited stronger delayed-t ype hypersensitivity and cytotoxic-T-lymphocyte activity against HIV-1 (IIIB) compared to DNA alone. HIV-1-specific IgG subclass analysis sho wed that MPL tends to facilitate IgG2a production, suggesting enhancem ent of a predominant T-helper-type-1 response, and this enhancement ma y help to facilitate protective-antibody induction. Furthermore, a chl oramphenicol acetyltransferase (CAT) assay,vas employed to determine w hether MPL affected the gene expression process. Interestingly, both M PL preparations reduced CAT activity in the muscle injected with CAT e xpression vector but increased anti-CAT antibody production. These res ults indicate that MPL acts as an effective adjuvant for immunogenic D NA injection despite reduced expression of encoding protein in muscle. We conclude that MPL has a strong adjuvant effect on DNA vaccination against HIV-1.