Design of an immunogen containing multidimensionally conserved and immunogenic parts of the HIV proteome.

Despite decades of research, an effective HIV vaccine or cure has not yet been developed. An important reason is the virus's mutability, which allows it to rapidly evade human immune responses. Often, the virus also takes advantage of epistatic pathways to evolve escape mutations through compensatory effects that allow maintaining its fitness. We used a fitness landscape of HIV, which explicitly considers interactions between mutations, to design an immunogen that contains parts of the proteome that are "multidimensionally" conserved. Based on inferred fitness landscapes, these regions are predicted to be under mutational constraints. Our immunogen also incorporates predicted immunogenic regions and offers broad coverage for the Caucasian population. We further investigate the relative contributions of various proteins in our design and compare properties with other immunogens. We hope that our proposed immunogen will serve as a candidate for experimental evaluation in pre-clinical studies in T cell-based vaccine or immunotherapy contexts.