Adjuvants and delivery systems for viral vaccines--mechanisms and potential

Of the vaccines against viral diseases of man currently available, several are less than satisfactory, and the present surge of interest in improving such vaccines, and in developing new vaccines against viral diseases as yet unchallenged, has led to major developments in three areas. The capacity to identify the nature and form of antigenic epitopes in proteins allows the specific design of molecular entities to promote relevant and protective immune responses. Such entities, although ideal in terms of specificity and purity, may not achieve their goals through failure to reach relevant cells of the immune system due to simple dilution, elimination by host enzymes or lack of specific targeting. Concomitant with the above there has been development of a plethora of adjuvants aimed at enhancing immune responses to these 'new' immunogens, paralleled by an almost equally rapid increase in understanding the complex nature of the immune response, particularly with respect to antigen processing, the nature and role of cytokines and the importance of T-cell subsets in infection. These developments allow exploration of matching the properties and mechanistic action of a given adjuvant to a defined immune response. Adjuvants can be grouped according to their physical characteristics and mode of action. They include particulate adjuvants, oil and emulsifier-based adjuvants, those providing controlled antigen delivery, adjuvants based on specific targeting of antigen, and gel-type adjuvants. They may act non-specifically in promoting an immune response to an antigen through depot formation, or very specifically as in a "delivery system" where an antigen is linked to a cellular protein, targeted to a specific cell receptor. As adjuvant technology develops it is becoming increasingly clear that these differing approaches may be combined, and an adjuvant/delivery system designed, to provide slow release of a targeted antigen. The role of adjuvants in modern viral vaccine technology and their influence on the immune system are the subject of this review.