Novel vaccine technologies for the 21st century

Novel approaches to vaccine development include structure-based immunogen design, gene-based vaccine platforms and formulation of recombinant antigens with potent adjuvants. These technologies are producing encouraging results in the development of vaccines for globally important diseases such as tuberculosis, influenza and respiratory syncytial virus. Here we highlight the most important developments in these areas over the past 18 months. New approaches to vaccine development have generated exciting results over the past 18 months. Focusing on respiratory syncytial virus infection, influenza and tuberculosis, Fauci and Mascola discuss the impact of structure-based vaccine design, gene-based vaccine platforms and advances in adjuvant development. Key advances The atomic level structure of the viral surface fusion protein of respiratory syncytial virus provided key insights that enabled the production of a stabilized subunit vaccine candidate that elicited robust immunogenicity in a phase I study. Technical advances in mRNA vaccines have led to improved intracellular stability and antigen expression, leading to robust and durable immune responses. mRNA candidate vaccines encoding full length haemagglutinin from two pandemic influenzas strains were safe and immunogenic in phase I studies. A tuberculosis (TB) subunit recombinant fusion protein (M72) formulated with a potent adjuvant (ASO1E) was effective at preventing activation of pulmonary TB in latently infected adults. Bacillus Calmette-Guérin (BCG) revaccination of uninfected adolescents provided protection against Mycobacterium tuberculosis infection.