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Mutational escape from vaccine induced immune responses has thwarted thedevelopment of a successful vaccine against AIDS, whose causative agent is HIV,a highly mutable virus. Knowing the virus' fitness as a function of itsproteomic sequence can enable rational design of potent vaccines, as thisinformation can focus vaccine induced immune responses to target mutationalvulnerabilities of the virus. Spin models have been proposed as a means toinfer intrinsic fitness landscapes of HIV proteins from patient-derived viralprotein sequences. These sequences are the product of non-equilibrium viralevolution driven by patient-specific immune responses, and are subject tophylogenetic constraints. How can such sequence data allow inference ofintrinsic fitness landscapes? We combined computer simulations and variationaltheory \'{a} la Feynman to show that, in most circumstances, spin modelsinferred from patient-derived viral sequences reflect the correct rank order ofthe fitness of mutant viral strains. Our findings are relevant for diverseviruses.

Spin models inferred from patient data faithfully describe HIV fitness landscapes and enable rational vaccine design