EFFECTS OF ADJUVANTS AND MULTIPLE ANTIGEN PEPTIDES ON HUMORAL AND CELLULAR IMMUNE-RESPONSES TO GP160 OF HIV-1

The capacity of five different adjuvants, AlPO4, a muramyldipeptide fo rmulation (MDP.TSL), Freund's adjuvant, immunostimulating complex and its matrix components to elicit humoral and cellular responses in rabb its immunized with the human immunodeficiency virus type 1 (HIV-1) env elope protein rgp160IIIB was compared. The highest antibody titers aga inst gp160 and gp41/gp120 epitopes were seen with rgp160 in MDP.TSL or Freund's adjuvant, whereas the broadest responses were seen in rabbit s immunized with rgp160 in matrix or MDP.TSL. The broadest spectrum of high-avidity antibodies was also induced by rgp160 in MDP.TSL. Neutra lizing titers against HIV-1IIIB, low titers to HIV-1MN, and the most e fficient inhibition of viral cell-to-cell spread was seen with rgp160 in MDP.TSL. The strongest and most persisting cellular responses were induced by rgp160 in AlPO4 or MDP.TSL. Using MDP.TSL as the adjuvant, we also improved the immune response against gp120 epitopes by boostin g rgp160-primed rabbits with rgp160, multiple antigenic peptides (MAPs ), or unconjugated peptides. The MAPs induced high neutralizing titers and were superior to rgp160 alone in inducing both humoral and cellul ar reactivity. MAPs are therefore strong candidates for inclusion into future HIV-1 vaccines.