Genomic Diversity of Pneumococcal Surface Protein A Clades distribution among vaccine and non-vaccine serotypes and association with antimicrobial resistance; implications for next-generation pneumococcal vaccine design
Pneumococcal conjugate vaccines have substantially reduced invasive pneumococcal disease, but their effectiveness is undermined by serotype replacement and limited coverage of the over 100 known serotypes, driving demand for serotype-independent vaccine antigens. Pneumococcal surface protein A (PspA), classified into six clades grouped into three families, is a conserved surface-exposed antigen that could circumvent both limitations. We investigated PspA clade distribution in 321 pneumococcal isolates collected between 2006 and 2024 from Pakistan and examined associations with serotype, sequence type (ST), global pneumococcal sequence cluster (GPSC), and antimicrobial resistance (AMR). Clade 1 was the most prevalent (n=118, 36.8%), followed by clade 3 (n=76, 23.7%), clade 2 (n=45, 14.0%), clade 5 (n=43, 13.4%), and clade 4 (n=34, 10.6%), with over 98% of isolates belonging to PspA families 1 and 2. While PspA clades showed considerable diversity within serotypes, their distribution was strongly concordant with ST and GPSC groupings (p<0.01), confirming clonal rather than serotype-driven clade composition. PspA clade distribution remained stable across pre- and post-PCV periods (?²=3.02, p=0.555), despite serotype-level shifts under vaccine pressure. We also report the first evidence of an association between PspA clades and AMR, with clade 3 identified as the predominant MDR reservoir among pneumococcal isolates in Pakistan. These findings support PspA as a stable, broadly protective vaccine antigen with potential to curb antimicrobial resistance and extend coverage beyond current PCV limitations.
Pneumococcal conjugate vaccines have substantially reduced invasive pneumococcal disease, but their effectiveness is undermined by serotype replacement and limited coverage of the over 100 known serotypes, driving demand for serotype-independent vaccine antigens. Pneumococcal surface protein A (PspA), classified into six clades grouped into three families, is a conserved surface-exposed antigen that could circumvent both limitations. We investigated PspA clade distribution in 321 pneumococcal isolates collected between 2006 and 2024 from Pakistan and examined associations with serotype, sequence type (ST), global pneumococcal sequence cluster (GPSC), and antimicrobial resistance (AMR). Clade 1 was the most prevalent (n=118, 36.8%), followed by clade 3 (n=76, 23.7%), clade 2 (n=45, 14.0%), clade 5 (n=43, 13.4%), and clade 4 (n=34, 10.6%), with over 98% of isolates belonging to PspA families 1 and 2. While PspA clades showed considerable diversity within serotypes, their distribution was strongly concordant with ST and GPSC groupings (p<0.01), confirming clonal rather than serotype-driven clade composition. PspA clade distribution remained stable across pre- and post-PCV periods (?²=3.02, p=0.555), despite serotype-level shifts under vaccine pressure. We also report the first evidence of an association between PspA clades and AMR, with clade 3 identified as the predominant MDR reservoir among pneumococcal isolates in Pakistan. These findings support PspA as a stable, broadly protective vaccine antigen with potential to curb antimicrobial resistance and extend coverage beyond current PCV limitations.
Lahore University of Management Sciences