Design and selection of vaccine adjuvants: principles and practice

Abstract

Experience has shown that the initiation, quality, and magnitude of the immune response to a vaccine antigen can be influenced by numerous factors. These include the type and dose of the antigen, the timing of immunization and boosting, the route of immunization, and even the age and general health of the vaccinee. Addition of an adjuvant to the vaccine formulation to enhance the immune response in a safe and nonspecific manner has also been a strategy that has been successfully employed for many vaccines. In past years, and even to the present, this has been accomplished mainly through adsorption of the antigen to an aluminum salt [1-3]. However, it should be noted that aluminum salts generally perform only weakly as adjuvants, particularly for booster immunizations, even though they do have a relatively good record of safety. Modern research has demonstrated that different adjuvants can have profound effects not only on the magnitude of the immune response, but also on the qualitative type of immune response. Two illustrative examples of this are given below. In the first example, among many that could be cited, differences in protection against Mycobacterium tuberculosis challenge in mice were induced by different adjuvant formulations [4]. In this study it was found that injection of recombinant mycobacterial 65 kDa heat shock protein (hsp65) as an antigen by itself was unable to protect mice, even with Freund's incomplete adjuvant. However, when the antigen was administered as a DNA vaccine or as a recombinant protein entrapped in cationic liposomes, protection was observed. In contrast, when hsp65 was encapsulated in polymeric microspheres for sustained release of antigen, high levels of specific antibody were observed but the mice were not protected after challenge.