Comparative Vaccinomics of Streptococcus pneumoniae Serotypes Causing Invasive Disease in Nigerian Children: Implications for Pneumococcal Conjugate Vaccine Strategy

Pneumococcal conjugate vaccines (PCVs) have dramatically reduced invasive pneumococcal disease in high-income countries, but serotype replacement and geographic serotype heterogeneity limit their effectiveness in sub-Saharan Africa. This comparative vaccinomics study characterized the full spectrum of Streptococcus pneumoniae serotypes causing invasive disease in Nigerian children under five years, assessed PCV10 and PCV13 coverage, and predicted the potential impact of higher-valency vaccines using epidemiological modeling. Children with culture-confirmed invasive pneumococcal disease were enrolled at six pediatric tertiary hospitals across the North West (Kano), North East (Maiduguri), North Central (Abuja), South West (Lagos), South East (Enugu), and South South (Port Harcourt) zones over 36 months. Serotyping was performed by the Quellung reaction and PCR. Whole-genome sequencing was conducted on a representative subset to analyze serotype-associated virulence gene profiles and antibiotic resistance determinants. A total of 280 invasive pneumococcal disease isolates were characterized. PCV13-covered serotypes accounted for 61.4 percent of isolates nationally, but coverage ranged from 48 percent in the South East to 71 percent in the North West. Non-PCV13 serotypes 15B/C, 23A, and 35B collectively accounted for 18.2 percent of isolates. Genomic analysis linked serotype 19A with the greatest virulence gene burden. Epidemiological modeling predicted that PCV20 would increase coverage to 79.6 percent nationally. These findings provide a vaccinomics foundation for Nigeria's PCV strategy review and advocate for PCV20 adoption and sustained serotype surveillance. Keywords: Streptococcus pneumoniae, vaccinomics, serotype, pneumococcal conjugate vaccine, Nigeria.