Abstract
Since it became available as a routine tool in biology, the determination and analysis of nucleotide sequences has been applied to the design of vaccines and the investigation of their effectiveness. As vaccination is primarily concerned with the interaction of biological molecules with the immune system, the utility of sequence data is not immediately obvious and, indeed, nucleotide sequence data are most effective when used to complement more conventional immunological approaches. Here, the impact of sequencing on the field of vaccinology will be illustrated with reference to the development and implementation of vaccines against Neisseria meningitidis (the meningococcus) over the 30-year period from the late-1980s to the late-2010s. Nucleotide sequence-based studies have been important in the fight against this aggressive pathogen largely because of its high genetic and antigenic diversity, properties that were only fully appreciated because of sequence-based studies. Five aspects will be considered, the use of sequence data to: (i) discover vaccine antigens; (ii) assess the diversity and distribution of vaccine antigens; (iii) determine the evolutionary and population biology of the organism and their implications for immunization; and (iv) develop molecular approaches to investigate pre- and post-vaccine pathogen populations to assess vaccine impact. One of the great advantages of nucleotide sequence data has been its scalability, which has meant that increasingly large data sets have been available, which has proved invaluable in the investigation of an organism as diverse and enigmatic as the meningococcus.
Highlights
The 40 years following the introduction of the Sanger dideoxy method in 1977 [1] saw a revolution in biology, which was driven by the improvement of nucleotide sequencing technologies
Many of the most successful bacterial and viral vaccines were developed in the mid- to late- twentieth century, without recourse to the detailed genetic information that nucleotide sequencing provides; most of these conventionallydeveloped vaccines targeted antigenically stable pathogens, such as the smallpox virus, or those that rely on a single, stable, molecule for their pathogenicity, such as Corynebacterium diphtheriae and Clostridium tetani
The recognition of the importance of horizontal genetic transfer (HGT) in bacterial evolution came from studies of antibiotic resistance and vaccine antigens in the gonococcus [23], meningococcus [22], and pneumococcus [24], with a major impact on our understanding on bacterial population biology and evolution [25]
Summary
As vaccination is primarily concerned with the interaction of biological molecules with the immune system, the utility of sequence data is not immediately obvious and, nucleotide sequence data are most effective when used to complement more conventional immunological approaches. Five aspects will be considered, the use of sequence data to: (i) discover vaccine antigens; (ii) assess the diversity and distribution of vaccine antigens; (iii) determine the evolutionary and population biology of the organism and their implications for immunization; and (iv) develop molecular approaches to investigate pre- and post-vaccine pathogen populations to assess vaccine impact. One of the great advantages of nucleotide sequence data has been its scalability, which has meant that increasingly large data sets have been available, which has proved invaluable in the investigation of an organism as diverse and enigmatic as the meningococcus
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