Advances and controversies in yellow fever vaccination

Ever since its development in 1937, the live-attenuated 17D yellow fever (YF) vaccine has been one of the most effective vaccines available to man. In this review we highlight the major steps in the development of 17D YF vaccine. We discuss the use of neutralizing antibodies as a surrogate marker for protection, and explore the strengths and weaknesses of the current plaque reduction neutralization test (PRNT), a technique developed in the 1960s that continues to be superior to every modern test in both sensitivity and specificity. The neutralizing antibodies demonstrated by the PRNT can be detected for several decades after vaccination, possibly even for the remainder of the recipient's natural life. We review the available evidence on the duration of protection after primary vaccination, a topic that has been the subject of controversy over the last few months. For persons who are immunocompromised due to disease, medication or advancing age, the duration of protection may be shorter: they should always have their vaccine response checked by PRNT. Due to the higher risk of severe adverse events after vaccination with 17D YF in this group, the development of a new, inactivated vaccine will have substantial benefits in this population.