Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines.

ABSTRACT

One of the great demands and challenges for vaccination is to successfully target the pathogens responsible for much of mankind's chronic disease burden including AIDS, infectious hepatitis, tuberculosis and malaria. Another is realizing the potential of therapeutic immunization to cure diseases such as cancer, allergy and inflammatory autoimmunity. To achieve these objectives, the fundamental insights gained from immunology, genomics, molecular-cellular biology and vaccinology must be implemented in order to develop more effective, better defined and safer vaccines. As an illustrative example of this we examine the key features of viruses that are known to be responsible for eliciting superb host immune responses. These insights have formed a basis for understanding the effectiveness of existing vaccines and provide a framework for designing and developing new vaccines better able to meet pressing unmet medical needs. The key immunogenic properties of viruses that are understood to date and are currently being applied include their particulate nature, their highly repetitive and ordered structures, their ability to induce innate immunity with consequent conditioning of adaptive responses and the kinetics and distribution of viral antigens during infection. Vaccines and vaccine-formulations recently registered for use in humans already incorporate some of these elements. Of great anticipation is the progress of the next-generation vaccines now advancing through the various stages of research and development. Vaccines which, by way of rational design, incorporate viral properties to induce tailored responses and thus have the potential to provide safer and more effective prophylaxis and therapies.