Vaccinology in the genome era
C. Daniela Rinaudo, … , Rino Rappuoli, Kate L. Seib
C. Daniela Rinaudo, … , Rino Rappuoli, Kate L. Seib
Published September 1, 2009
Citation Information: J Clin Invest. 2009;119(9):2515-2525. https://doi.org/10.1172/JCI38330.
View: Text | PDF
Review Series

Vaccinology in the genome era

Abstract

Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety.

Authors

C. Daniela Rinaudo, John L. Telford, Rino Rappuoli, Kate L. Seib

×

Figure 3

Flow chart of MenB vaccine development.

Options: View larger image (or click on image) Download as PowerPoint
Flow chart of MenB vaccine development. Preclinical development was base...
Preclinical development was based on a reverse vaccinology approach, in which the genome sequence of the virulent MenB strain MC58 was used to identify ORFs predicted to encode proteins that were surface exposed (i.e., secreted [S] or located in the outer membrane [OM]), which were then expressed in E. coli, purified, and used to immunize mice. Antibodies generated in mice were then used to confirm surface exposure of the vaccine candidate by FACS and to identify proteins that induced bactericidal activity. This screening process resulted in identification of several novel vaccine candidates, including GNA1870 (which is fHBP), GNA1994 (which is NadA), GNA2132, GNA1030, and GNA2091. The formulation for the comprehensive MenB vaccine consists of four components: fHBP-GNA2091 and GNA2132-GNA1030 fusion proteins, NadA, and OMV from the New Zealand MeNZB vaccine strain. Clinical development using this formulation has shown in phase I and II trials that the vaccine is well tolerated and immunogenic. The vaccine induced bactericidal activity using human complement (hSBA) with titers greater than 1:4, which indicates the generation of antibodies able to kill the bacteria at a level that correlates with protection against the bacteria, in more than 90% of infants after the fourth dose. This vaccine entered phase III clinical trials in 2008. P, periplasm; IM, inner membrane; C, cytoplasm.