TY - JOUR
T1 - The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome
AU - Azarian, Taj
AU - Grant, Lindsay R.
AU - Arnold, Brian J.
AU - Hammitt, Laura L.
AU - Reid, Raymond
AU - Santosham, Mathuram
AU - Weatherholtz, Robert
AU - Goklish, Novalene
AU - Thompson, Claudette M.
AU - Bentley, Stephen D.
AU - O’Brien, Katherine L.
AU - Hanage, William P.
AU - Lipsitch, Marc
N1 - Funding Information:
This study was supported by R01 R01AI048935, the Grand Challenges in Global Health initiative through the Bill & Melinda Gates Foundation, the Native American Research Centers for Health (U26IHS300013/03), the Centers for Disease Control and Prevention National Vaccine Program Office, and the Thrasher Research Fund (02820-9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to acknowledge the core informatics, library-making, and sequencing teams at the Wellcome Trust Sanger Institute. Furthermore, the authors express their appreciation to the individuals in the Navajo and White Mountain Apache communities who participated in the studies. We also gratefully acknowledge the dedicated efforts of the Center for American Indian Health field staff who collected these data over many years.
Publisher Copyright:
© 2018 Azarian et al.
PY - 2018/4
Y1 - 2018/4
N2 - In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998–2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998–2000) than the preceding period (2006–2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal vaccines.
AB - In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998–2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998–2000) than the preceding period (2006–2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal vaccines.
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U2 - 10.1371/journal.ppat.1006966
DO - 10.1371/journal.ppat.1006966
M3 - Article
C2 - 29617440
AN - SCOPUS:85046415236
VL - 14
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 4
M1 - e1006966
ER -