Adjuvants and delivery issues related to immunization: a survey of the recent patent literature.

Vaccines have provided generations of individuals with protection against a number of devastating childhood diseases and, in the case of smallpox, have eradicated the disease. Arguably, this preventive approach to health care may have saved more lives than all other therapeutic approaches combined. Being commonly composed of killed-whole or live-attenuated organisms, successful vaccines have been capable of not only presenting crucial epitopes required for protective immunity but also components which stimulate the immune system provide a response of sufficient intensity to provide sustained protection. It is unlikely, however, that these same vaccines would be approved in today's regulatory climate where manufacturers must validate a highly reproducible manufacturing process and demonstrate the exact composition of the final product through stringent quality control (Gupta, 1997). Therefore, companies involved in the identification of new vaccines and their production appear to be moving away from the ill-defined and poorly-controlled immunogens of the past. Instead, they have started employing recombinant biotechnology to produce large quantities of specific antigens with the hope that these antigens will provide protective immunity. Antigen identification can take years of investigation. This process could be speeded up, however, by understanding the mechanisms which pathogens such as viruses and bacteria use to infect the host, their replication cycle and the steps they frequently take to evade the host immune system. Such a rational approach to immunogen design results in what has been termed an "intelligent" vaccine (Plough, 1998). "Intelligent" vaccines will likely be completely composed of artificial or synthetically derived products using recombinant and cell culture technologies and hopefully will allow manufacturers to develop products with the desired efficacy and safety profiles required by regulatory authorities. But unlike the complex and ill-defined immunogens of the past, these specific antigens are frequently poorly antigenic by themselves when compared to whole organisms. Co-delivery with a variety of agents, known as adjuvants, has been shown to increase the antigenicity of these poorly antigenic immunogens. In this editorial, I review the recent patent literature as it pertains to targeting of specific antigens and the role played by various classes of adjuvants to enable or enhance such targeted deliveries.