Modulation of HIV-1 immunity by adjuvants

Moody, M. Anthony

Concurrent with the development of vaccine candidates, numerous animal and human studies compared available adjuvants in head-to-head trials. No clearly superior regimen was identified, likely because of the lack of a consistent immunogen across trials along with differing immunization schemes and different outcome measures. For example, Mannhalter et al. [19] in 1991 reported the immunization of chimpanzees with a recombinant envelope (Env) gp160 using alum, a water-inoil emulsion (termed lipid-based adjuvant), or alum plus deoxycholate. T-cell responses were best for the lipid-based adjuvant and were shown to last for months after the final immunization; antibody responses were not reported. Niedrig et al. [12] reported in 1993 on another group of chimpanzees immunized with formaldehyde-inactivated HIV-1 adjuvanted with alum, Freund's incomplete adjuvant (an oil-in-water emulsion), or with a zinc hydroxide/lecithin-based adjuvant; in this study, antibody titers were best with the lecithin-based adjuvant, although proliferation and antibodydependent cell-mediated cytotoxicity (ADCC) responses were similar between lecithin and alum arms. Levi et al. [20] reported in 1993 a comparison in rabbits of alum, Iscom, Iscomatrix, muramyl dipeptide (MDP), and Freund's complete adjuvant with a recombinant gp160 as the immunogen. Antibody titers were highest with Freund's complete adjuvant and MDP. During the same time period, numerous mouse studies were published and nearly all demonstrated that one adjuvant was superior. These and other head-to-head studies of vaccines are shown in Table 1 [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] .