Immunology and Early Phase Trials

Abstract

The biological basis of successful vaccination is our own complex immune system and its response to pathogens. Vaccination can induce an immune response that mimics natural infection or tries to do even better than our response to a pathogen. Vaccination induces an immune response in the individual vaccinated. A population of hosts has a collective level of immunity that results from the level of immunity in the individuals that compose it. The collective immunological status of a population of hosts, as opposed to an individual host, with respect to a given pathogen is called herd immunity. Maintenance of individual immunity can depend on repeated boosting by natural infection. The level of transmission may be diminished by high levels of immunization or natural immunity in a population to the point that natural boosting of immunity does not occur. Thus for some infections, a complex interplay between individual and population level immunity is maintained through the dependent happenings.

The immune response is also the source of many safety considerations of vaccination. Before a vaccine can be shown efficacious against infection or disease in a large-scale field study, it must be shown to elicit an immune response and to be safe in smaller studies. The design and analysis of vaccine studies requires an understanding of immunology and vaccines that goes beyond the scope of this book. Our goal in this chapter is to present sufficient biological background and terminology that the other chapters of the book can be read and understood. The key ideas are the immunogenicity and safety of vaccines. Preclinical studies in animals and Phase I and II clinical studies in humans have the primary goals of assessing the immunogenicity and safety of vaccine candidates. Early phase studies as well as experimental challenge studies are discussed briefly in this chapter. Population-level considerations include herd immunity and natural boosting of immunity.