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Technological advances, together with a better understanding of the molecular biology of infectious microorganisms, are creating exciting possibilities for a new generation of replicating vaccines. Historically, live vaccines have been either directly derived from a natural source or attenuated by empirical approaches using serial passages and host cell adaptation. Currently, we are witnessing a quantum leap in our technological capabilities to specifically modify the genetic make-up of viruses and bacteria, making it possible to generate improved live vaccines and to develop completely new types of replicating vaccines, such as vectored vaccines, single-round infectious vaccines and replicon vaccines. This book highlights some of the most exciting recent developments towards a new generation of replicating vaccines.