The Control of the Antibody Isotype Response to Recombinant Human Immunodeficiency Virus gp120 Antigen by Adjuvants

Abstract

Both saponin and muramyl dipeptide (MDP) formulated with a squalane-in-water emulsion of large particle size prepared with a vortex mixer were superior to Al(OH)₃ as adjuvants for HIV gp120 in mice. All the adjuvants induced IgG₁ antibody, but saponin elicited the highest titers of IgG_2a. The secretion of interleukin-5 (IL-5) and interferonγ (IFNγ) by lymph node cells cultured in vitro with gp120 was studied. All the cultures secreted IL-5, but only those from saponin-immunized mice produced IFNγ, suggesting that saponin is capable of activating both the Th1 and TH2 T-cell subsets. The titers of neutralizing antibodies were low with both MDP and saponin, and they occurred in mice which were also positive for antibodies against a V3 loop peptide. Glucosaminylmuramyl dipeptide (GMDP) which is less pyrogenic than MDP and a nonpyrogenic analog GMDPA, displayed equivalent adjuvant activity to MDP. The level and isotype composition of antibodies induced by GMDP in combination with squalane emulsions depended on the dimension of the emulsion particles. With a large (2500 nm) particle size the response was confined to IgG₁ in Balb/c mice, but when this was reduced to 150 nm by sonication the antibody response was increased and relatively high levels of IgG_2a appeared in some mice.