Nonclassically Secreted Proteins as Possible Antigens for Vaccine Development: A Reverse Vaccinology Approach

Reverse vaccinology strategies have already been applied to a variety of microorganisms and have contributed significantly to vaccine development. However, most of the studies focused on an individual organism or on proteins with signature sequence motifs commonly found in known secreted proteins from bacteria. In this work, we applied a reverse vaccinology strategy based on conservation, virulence, and nonclassically surface exposure criterions to identify potential antigens in two microorganisms with significant degree of genomic plasticity among isolates (Streptococcus pneumoniae and Leptospira spp.), which imposes a major limitation to the production of a multistrain component vaccine. PSORTb 3.0.2 was run to predict the subcellular localization of the proteins. OrthoMCL was run to identify groups of the most conserved proteins between strains. Virulence prediction was done for the most conserved proteins, and SecretomeP was run to predict the nonclassically secreted proteins among the potential virulence factors. Based on the above criteria, we identified 37 proteins conserved between 16 genomes of S. pneumoniae and 12 proteins conserved between 5 leptospiral genomes as potential vaccine candidates.