TY - JOUR
T1 - The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1
AU - Cornick, Jennifer E.
AU - Tastan Bishop, Özlem
AU - Yalcin, Feyruz
AU - Kiran, Anmol M.
AU - Kumwenda, Benjamin
AU - Chaguza, Chrispin
AU - Govindpershad, Shanil
AU - Ousmane, Sani
AU - Senghore, Madikay
AU - du Plessis, Mignon
AU - Pluschke, Gerd
AU - Ebruke, Chinelo
AU - McGee, Lesley
AU - Sigaùque, Beutel
AU - Collard, Jean Marc
AU - Bentley, Stephen D.
AU - Kadioglu, Aras
AU - Antonio, Martin
AU - von Gottberg, Anne
AU - French, Neil
AU - Klugman, Keith P.
AU - Heyderman, Robert S.
AU - Alderson, Mark
AU - Everett, Dean B.
N1 - Funding Information:
Authors thank David K. Brown for assisting with the running of SNP tools in local machines and the contributors of isolates to the Global Strain Bank, a project funded by PATH. Benjamin Kumwenda thanks Rhodes University for their hospitality.
Publisher Copyright:
© 2017 The Authors
PY - 2017/2/7
Y1 - 2017/2/7
N2 - 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.
AB - 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.
KW - Antigenic diversity
KW - Antigenic profiling
KW - Multi-valent
KW - PCV
KW - Pneumococcal disease
KW - Protein modelling
KW - Structural diversity
KW - Variant
UR - http://www.scopus.com/inward/record.url?scp=85009179793&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2016.12.037
DO - 10.1016/j.vaccine.2016.12.037
M3 - Article
C2 - 28081968
AN - SCOPUS:85009179793
SN - 0264-410X
VL - 35
SP - 972
EP - 980
JO - Vaccine
JF - Vaccine
IS - 6
ER -
