Abstract
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.
Highlights
Streptococcus pneumoniae is a human nasopharyngeal commensal that can invade normally sterile sites to cause invasive pneumococcal disease (IPD), including bacteraemia and meningitis [1]
Variant-1 was not identified in the European population; SP0148 variant-2 and -3 were present in 75% (21/28) and 25% (7/28) of the European population, respectively
We first investigated the prevalence of seven of the most promising vaccine protein candidates (PhtD, pneumococcal-binding protein A (PcpA), CbpA, pneumococcal surface protein C (PspC), SP2108, SP1912 and SP0148) in the largest sequenced collection of a single serotype to date; 445 serotype 1 pneumococci isolated from four different continents, with a specific focus on isolates recovered from Africa, where serotype 1 arguably causes the greatest disease burden
Summary
Streptococcus pneumoniae is a human nasopharyngeal commensal that can invade normally sterile sites to cause invasive pneumococcal disease (IPD), including bacteraemia and meningitis [1]. There are >90 pneumococcal serotypes, each of which produce a biochemically distinct capsular polysaccharide (CPS) and vary in propensity to cause invasive disease [4]. Serotype 1 is one of the most common causes of IPD worldwide. In Africa, it is responsible for 11.7% of all IPD cases [5]. In contrast to other serotypes, serotype 1 is associated with outbreaks in closed communities [6] and lethal meningitis outbreaks in West Africa [7,8]. The 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) have been rolled out across Africa with support from the GAVI alliance (www.gavi.org), both formulations incorporate serotype 1, the full impact of these vaccines across the continent is not yet known [9]
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