Comparative genomics of whole-cell pertussis vaccine strains from India

Abstract

Background: Despite high vaccination coverage using acellular (ACV) and whole-cell pertussis (WCV) vaccines, the resurgence of pertussis is observed globally. Genetic divergence in circulating strains of Bordetella pertussis has been reported as one of the contributing factors for the resurgence of the disease. Our current knowledge of B. pertussis genetic evolution in circulating strains is mostly based on studies conducted in countries using ACVs targeting only a few antigens used in the production of ACVs. To better understand the adaptation to vaccine-induced selection pressure, it will be essential to study B. pertussis populations in developing countries which are using WCVs. India is a significant user and global supplier of WCVs. We report here comparative genome analyses of vaccine and clinical isolates reported from India. Whole-genome sequences obtained from vaccine strains: WCV (J445, J446, J447 and J448), ACV (BP165) were compared with Tohama-I reference strain and recently reported clinical isolates from India (BPD1, BPD2). Core genome-based phylogenetic analysis was also performed using 166 isolates reported from countries using ACV. Results: Whole-genome analysis of vaccine and clinical isolates reported from India revealed high genetic similarity and conserved genome among strains. Phylogenetic analysis showed that clinical and vaccine strains share genetic closeness with reference strain Tohama-I. The allelic profile of vaccine strains (J445:ptxP1/ptxA2/prn1/fim2-1/fim3-1; J446: PtxP2/ptxA4/prn7/fim2-2/fim3-1; J447 and J448: PtxP1/ptxA1/prn1/fim2-1/fim3-1), which matched entirely with clinical isolates (BPD1:ptxP1/ptxA1/prn1/fim2-1 and BPD2: PtxP1/ptxA1/prn1/fim2-1) reported from India. Multi-locus sequence typing (MLST) demonstrated the presence of dominant sequence types ST2 and primitive ST1 in vaccine strains which will allow better coverage against circulating strains of B. pertussis. Conclusions: The study provides a detailed characterization of vaccine and clinical strains reported from India, which will further facilitate epidemiological studies on genetic shifts in countries which are using WCVs in their immunization programs.