title: Influence of protein fold stability on immunogenicity and its implications for vaccine design.
abstract: In modern vaccinology and immunotherapy, recombinant proteins more and more replace whole organisms to induce protective or curative immune responses. Structural stability of proteins is of crucial importance for efficient presentation of antigenic peptides on MHC, which plays a decisive role for triggering strong immune reactions. Areas covered: In this review, we discuss structural stability as a key factor for modulating the potency of recombinant vaccines and its importance for antigen proteolysis, presentation, and stimulation of B and T cells. Moreover, the impact of fold stability on downstream events determining the differentiation of T cells into effector cells is reviewed. We summarize studies investigating the impact of protein fold stability on the outcome of the immune response and provide an overview on computational methods to estimate the effects of point mutations on protein stability. Expert commentary: Based on this information, the rational design of up-to-date vaccines is discussed. A model for predicting immunogenicity of proteins based on their conformational stability at different pH values is proposed.
authors.affiliation: a Department of Molecular Biology , University of Salzburg , Salzburg , Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Scheiblhofer
authors.affiliation: a Department of Molecular Biology , University of Salzburg , Salzburg , Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Laimer
authors.affiliation: a Department of Molecular Biology , University of Salzburg , Salzburg , Austria.
authors.forename: Yoan
authors.initials: Y
authors.lastname: Machado
authors.affiliation: a Department of Molecular Biology , University of Salzburg , Salzburg , Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Weiss
authors.affiliation: a Department of Molecular Biology , University of Salzburg , Salzburg , Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology*; D004195:Disease Models, Animal; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry* / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
chemical_list: D000941:Antigens; D011994:Recombinant Proteins; D014612:Vaccines
keywords: Protein stability; conformational stability; destabilization; fold stability; immunogenicity; processing; protein variants; recombinant vaccines; stabilization