Reverse Vaccinology

Reverse Vaccinology

Nowadays vaccines can be designed based on the information encoded by the genome of a particular pathogen (Masignani et al., 2002; Rappuoli and Covacci, 2003). From many pathogens the entire genomes have been sequenced and this number is increasingly growing (http://www.sanger.ac.uk/ Projects/Pathogens). The genome sequence of a pathogen provides a complete picture of all proteins that can be produced by the pathogens at any given time. Using computer algorithms, proteins that are either excreted or expressed on the surface of the pathogen, and thus most likely available for recogni-tion by the host’s immune system, can be identified. After recombinant production and purification, these vaccine candidates can be screened for immunogeni-city in mice. From these, the best candidates can be selected and used as subunit vaccines (Fig. 9).

A big advantage of reverse vaccinology is the ease at which novel candidate antigens can be selected without the need to cultivate the pathogen. Furthermore, by comparing genomes of different strains of a pathogen, conserved antigens can be identified that can serve as a “broad spectrum” vaccine, giving protection against all strains or serotypes of a given pathogen. One drawback of thisapproach is that it is limited to the identification of protein-based antigens.

Reverse vaccinology has been successfully used to identify novel antigens for a variety of pathogens, including Neisseria meningitidis, Bacillus anthracis, Streptococcus pneumoniae, Staphylococcus aureus, Chlamydia pneumoniae and Mycobacterium tuberculosis.