Abstract
The best way to prevent diseases caused by pathogens is by the use of vaccines. The advent of genomics enables genome-wide searches of new vaccine candidates, called reverse vaccinology. The most common strategy to apply reverse vaccinology is by designing subunit recombinant vaccines, which usually generate an humoral immune response due to B-cell epitopes in proteins. A major problem for this strategy is the identification of protective immunogenic proteins from the surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena related to several human diseases. A sequence-based computational analysis has been carried out applying the BLASTP algorithm. Therefore, two huge databases have been created, one with the most complete and current linear B-cell epitopes, and the other one with the surface-protein sequences of the main human respiratory bacterial pathogens. We found that none of the 7353 linear B-cell epitopes analysed shares any sequence identity region with human proteins capable of generating antibodies, and that only 1% of the 2175 exposed proteins analysed contain a stretch of shared sequence with the human proteome. These findings suggest the existence of a mechanism to avoid autoimmunity. We also propose a strategy for corroborating or warning about the viability of a protein linear B-cell epitope as a putative vaccine candidate in a reverse vaccinology study; so, epitopes without any sequence identity with human proteins should be very good vaccine candidates, and the other way around.
Highlights
Vaccination is the preventive method of choice to fight against microbial pathogens and presents the best cost/benefit ratio among current clinical and pharmaceutical practices
With the aim of proposing a method applicable in a previous reverse vaccinology study, databases were made of the exposed proteins from the up-to-date, sequenced main human bacterial respiratory pathogens, which are: Neisseria meningitidis serogroup B, Legionella pneumophila (Lens strain), Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pyogenes serotype M1, Yersinia pestis, Bordetella bronchiseptica, Staphylococcus aureus (COL strain), Pasteurella multocida, Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae (Chlamydophila pneumoniae) and Mycoplasma pneumoniae
In terms of our study, after analysing the three database files of linear B-cell epitopes obtained via BLASTP [18], an exhaustive review of the output files obtained led us to the proposal that some selectivity really does exist to try to avoid auto-immunity
Summary
Vaccination is the preventive method of choice to fight against microbial pathogens and presents the best cost/benefit ratio among current clinical and pharmaceutical practices. Auto-immune diseases should appear if the exposed proteins of the bacterial pathogens share linear B-cell epitopes with any human protein, so this study may be useful to identify them [2,3] These findings may help us to identify proteins which should not be used as putative vaccine candidates in a reverse vaccinology study. We found several pathogen proteins which share sequence stretches with the host ones, so we recommend not to using these proteins as putative vaccine candidates in a reverse vaccinology study These proteins are a small group of the total surfome studied and they elicit antibodies with great difficulty, suggesting the same immunotolerance effect that tries to avoid autoimmunity mentioned here [12]
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