The Host Immune Response, Protective Immunity, and Correlates of Protection

The purpose of vaccines is to elicit vigorous and long-lasting immune responses against pathogen components that will protect recipients from disease should they be exposed to the pathogen. We now realize that developing appropriate B- and T-cell responses depends on appropriate activation of the innate immune response. Unlike T and B cells, which recognize very specific regions of pathogenic molecules through interaction with genetically rearranged receptors, innate immune cells recognize conserved molecular patterns inherent in pathogen-expressed molecules via an array of conserved, pattern recognition receptors. Engagement of these receptors results in release of inflammatory cytokines and in the activation and mobilization of innate immune cells. It also ultimately guides the activation and development of the adaptive immune response. The ability of the immune response to develop durable memory B- and T-cell responses specific for vaccine antigens forms the basis for immunization and vaccine-elicited immune protection. Recent progress in our understanding of how these memory responses are elicited and maintained should prove invaluable toward the development of improved vaccines. This chapter discusses how adaptive immune responses are elicited and links these processes to the development of protective immunity. The ways in which vaccine developers, manufacturers, and regulators utilize information about markers for protective immunity for a given vaccine is also discussed.