Review of Selected Adjuvants Used in Antibody Production

Immunologic adjuvants are agents that nonspecifically increase immune responses to specific antigens that are weakly immunogenic. The purpose of this article is to inform investigators and research staff about three commonly used and commercially available adjuvants for antibody production in laboratory animals and to briefly cover other adjuvants that may be used for this purpose. The three adjuvants that will be emphasized in this article are Freund's-type mineral oil adjuvant emulsions, Ribi Adjuvant System®, and TiterMax®. Other reports have studied these adjuvants, or combinations thereof, when administered with specific antigens (Lipman et al., 1992; Smith et al., 1992; Johnston et al., 1991). The objective of using adjuvants differs greatly, whether in research, antisera production, or vaccine development. Adjuvants intended for production of antisera need to induce high titers of high avidity antibody within a short time. Adjuvants intended for vaccine use need only induce protective titer, although the duration of the response and induction of immunologic memory are critical for maintaining protection. Induction of cell-mediated immunity is a requirement for protection against many etiologic agents, but is also partly responsible for side effects of adjuvants. Adjuvants or immunopotentiators were initially thought of as agents capable of promoting an augmented and more sustained antibody response. However, new evidence has shown that adjuvants influence titer, duration, isotype, and avidity of antibody, as well as affect properties of cell-mediated immunity (CMI) (Table 1) (Hunter et al., 1995). For example, adjuvants have been shown to induce class I-restricted CD8-positive cytotoxic T lymphocytes and modulate the specificity of antibody among available epitopes on protein antigens (Takahashi et al., 1990; Kenney et al., 1989). Adjuvants can be categorized according to their origins (whether they are derived from mineral; bacterial; plant; synthetic; or host product, such as Interleukin 1 and 2), and according to their proposed mechanism of action. Certain adjuvants such as alum, oil emulsions, liposomes, and synthetic polymers act through the effect of antigen localization ("depot" effect), which leads to slow delivery of the antigen. Most adjuvants also induce complex cell interactions between macrophages and lymphocytes.