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

Jennifer E. Cornick (1, 2) , Özlem Tastan Bishop (3) , Feyruz Yalcin (4) , Anmol M. Kiran (1, 2) , Benjamin Kumwenda (1) , Chrispin Chaguza (1, 2) , Shanil Govindpershad (5, 6) , Sani Ousmane (7) , Madikay Senghore (8, 9) , Mignon Du Plessis (5, 6) , Gerd Pluschke (10) , Chinelo Ebruke (8) , Lesley Mcgee (11) , Beutel Sigaùque (12) , Jean-Marc Collard (7) , Stephen D. Bentley (3) , Aras Kadioglu (2) , Martin Antonio (8, 9, 13) , Anne von Gottberg (5, 6) , Neil French (2) , Keith P. Klugman (14) , Robert S. Heyderman (1) , Mark Alderson (15) , Dean B. Everett (1, 2) , The Page Consortium

1 MLW - Malawi Liverpool Wellcome Trust Clinical Research Programme
2 University of Liverpool
3 Rhodes University, Grahamstown
4 The Wellcome Trust Sanger Institute [Cambridge]
5 NICD - National Institute for Communicable Diseases [Johannesburg]
6 WITS - University of the Witwatersrand [Johannesburg]
7 CERMES - Centre de Recherche Médicale et Sanitaire (Niamey, Niger)
8 MRC - Medical Research Council Unit The Gambia
9 University of Warwick [Coventry]
10 Swiss Tropical and Public Health Institute [Basel]
11 CDC - Centers for Disease Control and Prevention [Atlanta]
12 CISM - Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique]
13 LSHTM - London School of Hygiene and Tropical Medicine
14 Emory University [Atlanta, GA]
15 PATH [Seattle]

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.

Mots clés: Antigenic diversity; Antigenic profiling; Multi-valent; PCV; Pneumococcal disease; Protein modelling; Structural diversity; Variant

Domaines: Maladies infectieuses; Bactériologie; Santé publique et épidémiologie

Jennifer E. Cornick, Özlem Tastan Bishop, Feyruz Yalcin, Anmol M. Kiran, Benjamin Kumwenda, et al.. The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1. Vaccine, 2017, 35 (6), pp.972-980. ⟨10.1016/j.vaccine.2016.12.037⟩. ⟨pasteur-03238484⟩