| 摘要 |
Embodiments of the present invention include conserved-element vaccines and methods for designing and producing conserved-element vaccines. A conserved-element vaccine ("CEVac") is a recombinant and/or synthetic vaccine that incorporates only highly conserved epitopes from an observed set of pathogen variants. The conserved epitopes are identified computationally by aligning biopolymer sequences, such as concatenated polypeptide sequences that together represent a pathogen proteome, corresponding to an observed set of pathogen variants, and computationally selecting conserved subsequences according to a number of subsequence-selection criteria. These subsequence-selection criteria may include a minimum conserved-subsequence length, a threshold frequency of occurrence of a particular monomer at each conserved, single-monomer position within a conserved subsequence, a threshold combined occurrence for a set of allowable variant monomers at a particular conserved, variable position within a conserved subsequence, and a maximum number of variable positions within a subsequence. A set of conserved subsequences identified according to the subsequence-selection criteria are then filtered to remove subsequences identical to, or too similar to, naturally-occurring host subsequences, and are then assembled into expression vectors for incorporation into microbial hosts for biosynthesis of a recombinant CEVac or assembled into one or more synthetic constructs for a synthetic CEVac.
|
