Reverse immunodynamics: a new method to identifying targets of protective immunity.
Spensley K., Wikramaratna P., Penman B., Walker A., Smith A., Pybus O., Jean L., Gupta SUNETRA., Lourenco JOSE.
Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. We propose a novel methodology that combines predictions from epidemiological models with phylogenetic and structural analyses to identify such targets. Mathematical models predict that strong immune selection can cause antigenic variants to exist in non-overlapping combinations. A corollary of this theory is that targets of immunity may be identified by searching for non-overlapping associations among antigenic variants. We applied this concept to the AMA-1 protein of the malaria parasite Plasmodium falciparum and found strong signatures of immune selection among certain regions of low variability which could render them ideal vaccine candidates.