Scaffolding to build a rational vaccine design strategy

Conventional vaccines, going back to the work of Jenner and Pasteur, are based on a rather direct mimicry of the offending pathogen using an attenuated or killed version of the microbe or purified or recombinant proteins from the microbe surface. These vaccines have been enormously successful against a range of pathogens. However, the conventional approaches have faltered for other pathogens, such as HIV, that have evolved an arsenal of molecular tricks to avoid immune responses. In such cases, alternate strategies are being investigated. The report by Ofek et al. (1) in PNAS describes a promising approach for presenting a vaccine target in the context of a protein or “scaffold” that lacks some of the defensive features of a pathogen such as HIV. The report does not deliver an HIV vaccine, but it takes an important step forward.