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<p>The discovery of protective antigens remains a major bottleneck in bacterial vaccine development. To overcome this limitation, we present Functional Genomic Vaccinology (FGV), a high-throughput antigen discovery platform integrating genome-wide antigen prediction, proteome-scale screening, and experimental immunogenicity validation to identify protective bacterial antigens. Using FGV, 222 conserved <i>S. pneumoniae</i> proteins are expressed in vitro, incorporated into a protein microarray, and coupled to magnetic beads for mouse vaccination. Protein array analysis shows significant IgG responses in 40% of the screened proteins. Antigen-specific responses measured in human sera guide the prioritisation of 22 candidates, which undergo further studied for their serological and Th17 responses. Four antigens combined in a multicomponent vaccine induces protection from pneumonia and sepsis in mice, with epitope mapping revealing potential protective sites for each protein. These results establish FGV as a scalable, experimentally driven approach for bacterial vaccine discovery and demonstrate its applicability in developing protective pneumococcal vaccines.</p>

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High-throughput antigen discovery using Functional Genomic Vaccinology (FGV) identifies protective Streptococcus pneumoniae vaccine candidates

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月21日

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  • Giuseppe Ercoli,
  • Elisa Ramos-Sevillano,
  • Samantha Palethorpe,
  • Trisha Kerai,
  • Timothy Scott,
  • Rafael R. de Assis,
  • Aarti Jain,
  • Algis Jasinskas,
  • Rie Nakajima,
  • Jiin Felgner,
  • Stephanie W. Lo,
  • Brendan W. Wren,
  • Philip Felgner,
  • Jeremy S. Brown

摘要

The discovery of protective antigens remains a major bottleneck in bacterial vaccine development. To overcome this limitation, we present Functional Genomic Vaccinology (FGV), a high-throughput antigen discovery platform integrating genome-wide antigen prediction, proteome-scale screening, and experimental immunogenicity validation to identify protective bacterial antigens. Using FGV, 222 conserved S. pneumoniae proteins are expressed in vitro, incorporated into a protein microarray, and coupled to magnetic beads for mouse vaccination. Protein array analysis shows significant IgG responses in 40% of the screened proteins. Antigen-specific responses measured in human sera guide the prioritisation of 22 candidates, which undergo further studied for their serological and Th17 responses. Four antigens combined in a multicomponent vaccine induces protection from pneumonia and sepsis in mice, with epitope mapping revealing potential protective sites for each protein. These results establish FGV as a scalable, experimentally driven approach for bacterial vaccine discovery and demonstrate its applicability in developing protective pneumococcal vaccines.