Progress in the Development of Structure-Based Vaccines.

Abstract

The immune response elicited by vaccines against microorganisms makes it the most successful medical interventions against infectious diseases. Conventional vaccines have limitations in inducing immunity against many types of pathogenic microorganism. The genetic diversity of microorganisms, coupled with the high degree of sequence variability in antigenic proteins, presents a challenge to developing broadly effective conventional vaccines. Atomic-resolution structure determination is crucial for understanding antigenic protein function. Cryo-electron microscopy, nuclear magnetic resonance spectroscopy coupled with bioinformatics provide three-dimensional structure of the antigenic proteins and provide a wealth of information about the organization of individual atoms and their chemical makeup. The atomic detail information of proteins offers enormous potential to rationally engineer proteins to enhance their properties and act as effective immunogens to induce immunity. The observation that whole protein antigens are not necessarily essential for inducing immunity has led to the emergence "structural vaccinology." Structure-based vaccines are designed on the rationale that protective epitopes should be sufficient to induce immune responses and provide protection against pathogens. In 2013 we published a review on structure-based vaccines (Thomas and Luxon. Expert Rev Vaccines 12 1301-11, 2013). This review states the progress in development of structure-based vaccines since the first review.