J. Clin. Invest. https://doi.org/10.1172/JCI91512 (2018)

The stability of vaccines can be an important consideration for both their in vivo efficacy and their use in the field, which often necessitates a cold-chain deployment. In The Journal of Clinical Investigation, Sewell and colleagues use a synthetic-biology approach to generate a more stable peptide vaccine against influenza A virus. Nature tends to use l-amino acids; therefore, d-amino acid–based peptides can be more resistant to enzymatic digestion. Using a combinatorial peptide library, the authors generate a vastly more stable d-amino acid nonamer peptide that binds HLA-A2, albeit somewhat weakly, yet is able to robustly stimulate a protective influenza A virus–specific response in humanized mice. The d-amino acid peptide is also stable in a simulated gastric environment and is protective in vivo after oral vaccination.