Abstract
The ongoing, and very serious, threat from antimicrobial resistance necessitates the development and use of preventative measures, predominantly vaccination. Polysaccharide-based vaccines have provided a degree of success in limiting morbidity from disseminated bacterial infections, including those caused by the major human obligate pathogens, Neisseria meningitidis, and Streptococcus pneumoniae. Limitations of these polysaccharide vaccines, such as partial coverage and induced escape leading to persistence of disease, provide a compelling argument for the development of protein vaccines. In this review, we briefly chronicle approaches that have yielded licensed vaccines before highlighting reverse vaccinology 2.0 and its potential application in the discovery of novel bacterial protein vaccine candidates. Technical challenges and research gaps are also discussed.
Highlights
BACKGROUNDPrecedent to advancements in genomics, vaccines were developed based on Pasteur’s rules of vaccinology
VACCINE DISCOVERY IN THE PRE-WHOLE GENOME SEQUENCING (WGS) ERAPrecedent to advancements in genomics, vaccines were developed based on Pasteur’s rules of vaccinology
These capsular antigens have been conjugated to carrier proteins in a dose-sensitive manner for enhanced immunogenicity, as found in the Haemophilus influenzae type b (Hib) [8], pneumococcal
Summary
Precedent to advancements in genomics, vaccines were developed based on Pasteur’s rules of vaccinology. Bacterial capsular polysaccharides served as prime components of effective vaccines, used singly, for example, in the 23-valent pneumococcal polysaccharide vaccine, PPSV23 [7] These capsular antigens have been conjugated to carrier proteins in a dose-sensitive manner for enhanced immunogenicity, as found in the Haemophilus influenzae type b (Hib) [8], pneumococcal. The limited capacity of these hypothesis-driven studies to focus on only a handful of candidates at a time was costly in time, labor and financial terms This is especially because of the large pool from which prospective candidates for individual bacterial pathogens are screened, coupled with the low likelihood of targets satisfying key vaccine candidacy criteria (abundantly-expressed, surfaceexposed, functionally-immunogenic, and highly-conserved). Alternative high throughput methods were sought to accelerate the pre-clinical vaccine development phase, especially in situations requiring rapid curtailment of disease transmission
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