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Nora C Toussaint, Yaakov Maman, Oliver Kohlbacher, and Yoram Louzoun (2011)

Universal peptide vaccines – optimal peptide vaccine based on viral sequence conservation

Vaccine, 29(47):8745-8753.

Rapidly mutating viruses such as the hepatitis C virus (HCV), the human immunodeficiency virus (HIV), or influenza viruses (Flu) call for highly effective universal peptide vaccines, i.e. vaccines that do not only yield broad population coverage but also broad coverage of various viral strains. The efficacy of such vaccines is determined by multiple properties of the epitopes they comprise. Beyond the specific properties of each epitope, properties of the corresponding source antigens are of great importance. If a response is mounted against viral proteins with a low copy number within the cell or against proteins expressed very late, this response may fail to induce lysis of the infected cells before budding can take place. We here propose a novel methodology to optimize the epitope composition and position in order to induce a maximal protection. In order for a peptide vaccine to yield the best possible universal protection, several conditions should be met: (a) an optimal choice of target antigens, (b) an optimal choice of highly conserved epitopes, (c) maximal coverage of the target population, and (d) the proper ordering of the epitopes in the final vaccine to ensure favorable cleavage. We propose a mathematical formalism for epitope selection and ordering that balances the constraints imposed by these different conditions. Focusing on HCV, HIV, and Flu, we show that not all of the conditions can be fulfilled for all viruses. For each virus, different constraints are harder to maintain: In Flu, the conservation constraint is breached first, while in HIV, the targeting of optimal proteins is difficult to achieve. The proposed methodology can be applied to any virus to assess the feasibility of optimally combining the above-mentioned constraints.