Abstract
Many immunogens used in vaccine formulations, especially split (or subunit) virus preparations or proteins manufactured by genetic engineering, require the use of adjuvants to boost the immune response. Classical adjuvants include different kinds of emulsions, as well as aluminum derivatives such as aluminum hydroxide (Hem and White, 1984; and Chapter 9), aluminum phosphate (Hennessy et al., 1971), and aluminum oxide (Grafe and Kuhn, 1962a,b). Aluminum hydroxide adjuvants have been used most widely because of their reputation for safety in humans. Further, aluminum-based (“alum”) adjuvants are the only adjuvants currently included in vaccines licensed by the Food and Drug Administration (Hem and White, 1984). Despite alum’s common use, variations in alum quality frequently occur between different batches of the same aluminum hydroxide-adjuvanted vaccine. This inconsistent response is understandable in view of the structure of aluminum hydroxide (see Chapter 9). The structure and physicochemical properties of aluminum adjuvants change significantly with slight alterations in production conditions and with aging (Kreuter and Haenzel, 1978; Feldkamp et al., 1982; Nail et al., 1976a,b). With emulsions, the degree of dispersions defined as the particle size distribution of the inner-phase droplets, may vary from preparation to preparation and may also change after injection. For example, the droplet size may be decreased by frictional forces during injection into tight muscular tissues whereas injection into fatty tissues may result in a coalescence of the emulsion droplets, leading to a larger droplet (particle) size.