RESUMEN
Serotype 1 is one of the most common causes of pneumococcal disease worldwide. Pneumococcal protein vaccines are currently being developed as an alternate intervention strategy to pneumococcal conjugate vaccines. Pre-requisites for an efficacious pneumococcal protein vaccine are universal presence and minimal variation of the target antigen in the pneumococcal population, and the capability to induce a robust human immune response. We used in silico analysis to assess the prevalence of seven protein vaccine candidates (CbpA, PcpA, PhtD, PspA, SP0148, SP1912, SP2108) among 445 serotype 1 pneumococci from 26 different countries, across four continents. CbpA (76%), PspA (68%), PhtD (28%), PcpA (11%) were not universally encoded in the study population, and would not provide full coverage against serotype 1. PcpA was widely present in the European (82%), but not in the African (2%) population. A multi-valent vaccine incorporating CbpA, PcpA, PhtD and PspA was predicted to provide coverage against 86% of the global population. SP0148, SP1912 and SP2108 were universally encoded and we further assessed their predicted amino acid, antigenic and structural variation. Multiple allelic variants of these proteins were identified, different allelic variants dominated in different continents; the observed variation was predicted to impact the antigenicity and structure of two SP0148 variants, one SP1912 variant and four SP2108 variants, however these variants were each only present in a small fraction of the global population (<2%). The vast majority of the observed variation was predicted to have no impact on the efficaciousness of a protein vaccine incorporating a single variant of SP0148, SP1912 and/or SP2108 from S. pneumoniae TIGR4. Our findings emphasise the importance of taking geographic differences into account when designing global vaccine interventions and support the continued development of SP0148, SP1912 and SP2108 as protein vaccine candidates against this important pneumococcal serotype.
Asunto(s)
Variación Antigénica , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidad , África , Alelos , Secuencia de Aminoácidos , Antígenos Bacterianos/química , Antígenos Bacterianos/inmunología , Asia , Proteínas Bacterianas/química , Proteínas Bacterianas/inmunología , Europa (Continente) , Geografía , Salud Global , Humanos , Modelos Moleculares , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/patología , Infecciones Neumocócicas/virología , Vacunas Neumococicas/biosíntesis , Vacunas Neumococicas/genética , Vacunas Neumococicas/inmunología , Serogrupo , América del Sur , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología , Cobertura de Vacunación/estadística & datos numéricos , Vacunas de Subunidad , VirulenciaRESUMEN
Serotype 1 Streptococcus pneumoniae is a leading cause of invasive pneumococcal disease (IPD) worldwide, with the highest burden in developing countries. We report the whole-genome sequencing analysis of 448 serotype 1 isolates from 27 countries worldwide (including 11 in Africa). The global serotype 1 population shows a strong phylogeographic structure at the continental level, and within Africa there is further region-specific structure. Our results demonstrate that region-specific diversification within Africa has been driven by limited cross-region transfer events, genetic recombination and antimicrobial selective pressure. Clonal replacement of the dominant serotype 1 clones circulating within regions is uncommon; however, here we report on the accessory gene content that has contributed to a rare clonal replacement event of ST3081 with ST618 as the dominant cause of IPD in the Gambia.