The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1

• Type of Material: Article
• Authors: Jennifer E. Cornick, University of Liverpool; Özlem Tastan Bishop, Rhodes University; Feyruz Yalcin, Wellcome Trust Sanger Institute; Anmol M. Kiran, University of Liverpool; Benjamin Kumwenda, Queen Elizabeth Central Hospital; Chrispin Chaguza, University of Liverpool; Shanil Govindpershad, University of the Witwatersrand; Sani Ousmane, Centre de Recherche Médicale et Sanitaire; Madikay Senghore, The University of Warwick; Mignon du Plessis, University of the Witwatersrand; Gerd Pluschke, Swiss Tropical and Public Health Institute; Chinelo Ebruke, Medical Research Council; Lesley McGee, Centers for Disease Control and Prevention; Beutel Sigaùque, Centro de Investigação em Saúde da Manhiça; Jean-Marc Collard, Centre de Recherche Médicale et Sanitaire; Stephen D. Bentley, Rhodes University; Aras Kadioglu, University of Liverpool; Martin Antonio, London School of Hygiene and Tropical Medicine; Anne von Gottberg, University of the Witwatersrand; Neil French, University of Liverpool; Keith Klugman, Emory University; Robert S. Heyderman, Queen Elizabeth Central Hospital; Mark Alderson, PATH Seattle; Dean B. Everett, University of Liverpool
• Language: English
• Date: 2017-02-07
• Publisher: Elsevier: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Authors. Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2016.12.037
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 35
• Issue: 6
• Start Page: 972
• End Page: 980
• Grant/Funding Information: This work supported by the Bill and Melinda Gates Foundation (Grant No. OPP1023440), Wellcome Trust (Award No. 084679/Z/08/Z), National Research Foundation of South Africa (Grant No. 93690) and the NIH Common Fund Award (H3A Bionet) (Grant No. U41HG006941).
• Keywords: Antigenic diversity; Variant; Antigenic profiling; Protein modelling; Structural diversity; Pneumococcal disease; PCV; Multi-valent
• Research Categories: Health Sciences, Public Health; Biology, Virology; Biology, Microbiology

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.