From Jenner to genes--the next generation of virus vaccines.

Vaccination has played a major role in the control of many virus diseases affecting man and animals. Two kinds of vaccines are in use: (i) attenuated vaccines, which infect the host without causing disease and (ii) killed vaccines, which consist of large amounts of virus particles that have been inactivated by either physical or chemical agents under conditions that ensure retention of their antigenic properties. Despite the success of vaccination there is still a need for products that are safer and more effective. Even more important, there are diseases for which 'conventional' vaccines are not available. New approaches that will ultimately solve these problems have been provided by the detailed analysis of viruses at the molecular level. Thus we are now beginning to understand virulence in molecular terms and particularly rapid advances have been made with poliovirus, holding out the promise of a completely avirulent attenuated vaccine. With killed vaccines, the major advance has come from the recognition that the immune response to most viruses is determined by a single protein. By identifying the genes coding for these proteins it has become possible to express them in large quantities not only in a variety of cells, but also in virus vectors that can be grown in vitro and in vivo. Moreover, in some instances, fragments of immunogenic proteins, small enough to be synthesized chemically, have been shown to be protective. The rapid pace of these conceptual and technological advances leads the author to the expectation that viruses and antigens that are defined in precise chemical terms will form the basis of the vaccines of the future.