@article{b54b6dc5fe264610bf699b173f0bd90c,
title = "Emergence of double- and triple-gene reassortant G1P[8] rotaviruses possessing a DS-1-like backbone after rotavirus vaccine introduction in Malawi",
abstract = "To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunization programs. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunization schedule in 2012. Utilizing a surveillance platform of hospitalized rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 to 2012) and after (2013 to 2014) vaccine introduction. Analysis of whole genomes obtained through next-generation sequencing revealed that all randomly selected prevaccine G1P[8] strains sequenced (n = 32) possessed a Wa-like genetic constellation, whereas postvaccine G1P[8] strains (n = 18) had a DS- 1-like constellation. Phylodynamic analyses indicated that postvaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990s and hence were classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981 to 1994; their evolutionary rates ranged from 9.7 × 10-4 to 4.1 × 10-3 nucleotide substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation.",
keywords = "Genome reassortment, Lineage turnover, Malawi, Phylodynamics, Rotavirus, Whole-genome sequencing",
author = "{for the VacSurv Consortium} and Jere, {Khuzwayo C.} and Chrispin Chaguza and Naor Bar-Zeev and Jenna Lowe and Chikondi Peno and Benjamin Kumwenda and Osamu Nakagomi and Tate, {Jacqueline E.} and Parashar, {Umesh D.} and Heyderman, {Robert S.} and Neil French and Cunliffe, {Nigel A.} and Miren Iturriza-Gomara and Anthony Costello and Charles Mwansambo and James Beard and Crampin, {Amelia C.} and Carina King and Sonia Lewycka and Hazzie Mvula and Tambosi Phiri and Verani, {Jennifer R.} and Whitney, {Cynthia G.} and Louisa Pollock and Aisleen Bennett",
note = "Funding Information: K.C.J., N.B.-Z., and N. F. have received investigator-initiated research grant support from GlaxoSmithKline Biologicals. M.I.-G. has received investigator-initiated research Funding Information: grant support from GlaxoSmithKline Biologicals and Sanofi Pasteur Merck Sharpe & Dohme. O.N. has received research grant support and honoraria from Japan Vaccine and MSD for delivering lectures on rotavirus vaccines. N.A.C. has received research grant support and honoraria for participation in rotavirus vaccine advisory board meetings from GlaxoSmithKline Biologicals. All other authors report no potential conflicts. Funding Information: We thank the collaborating members of the VACSURV Consortium (Anthony Costello, Charles Mwansambo, James Beard, Amelia C. Crampin, Carina King, Sonia Lewycka, Hazzie Mvula, Tambosi Phiri, Jennifer R. Verani, Cynthia G. Whitney, Louisa Pollock, and Aisleen Bennett). We acknowledge the support of the laboratory staff at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme and the sequencing and informatics teams at the Centre for Genomic Research (CGR), University of Liverpool, United Kingdom. This work was supported by a research grant from GlaxoSmithKline Biologicals and the Wellcome Trust (program grant number 091909/Z/10/Z and the MLW Programme Core award). K.C.J. is a Wellcome Trust training fellow (grant number 201945/Z/16/Z). C.C. acknowledges funding from the Commonwealth Scholarship Commission (Ph.D. studentship). M.I.-G. is partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections. The research was funded by the NIHR HPRU in Gastrointestinal Infections at the University of Liverpool in partnership with Public Health England (PHE), the University of East Anglia, the University of Oxford, and the Institute of Food Research. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, or Public Health England. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of the manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The authors received no financial support or other form of compensation related to the development of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Centers for Disease Control and Prevention. K.C.J., N.B.-Z., and N. F. have received investigator-initiated research grant support from GlaxoSmithKline Biologicals. M.I.-G. has received investigator-initiated research grant support from GlaxoSmithKline Biologicals and Sanofi Pasteur Merck Sharpe & Dohme. O.N. has received research grant support and honoraria from Japan Vaccine and MSD for delivering lectures on rotavirus vaccines. N.A.C. has received research grant support and honoraria for participation in rotavirus vaccine advisory board meetings from GlaxoSmithKline Biologicals. All other authors report no potential conflicts. K.C.J., J.E.T., U.D.P., N.F., R.S.H., N.A.C. and M.I-G. conceived and designed the study. N.A.C and M.I.-G. supervised the study. K.C.J., N.B-Z., C.P., and N.A.C. collected the stool samples. K.C.J., J.L., and C.P. performed the laboratory work. K.C.J. and C.C. carried out the bioinformatic and statistical analyses and drafted the manuscript. B.K. and K.C.J. conducted protein modeling. K.C.J., C.C., N.B-Z., J.L., B.K., C.P., J.E.T., U.D.P., O.N., R.S.H., N.F., N.A.C., and M.I.-G. contributed to the discussions, interpretation of the results, and reviewing of the manuscript. Funding Information: This work was supported by a research grant from GlaxoSmithKline Biologicals and the Wellcome Trust (program grant number 091909/Z/10/Z and the MLW Programme Core award). K.C.J. is a Wellcome Trust training fellow (grant number 201945/Z/16/Z). C.C. acknowledges funding from the Commonwealth Scholarship Commission (Ph.D. studentship). M.I.-G. is partly supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections. The research was funded by the NIHR HPRU in Gastrointestinal Infections at the University of Liverpool in partnership with Public Health England (PHE), the University of East Anglia, the University of Oxford, and the Institute of Food Research. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, or Public Health England. The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of the manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation. The authors received no financial support or other form of compensation related to the development of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the U.S. Centers for Disease Control and Prevention. Publisher Copyright: {\textcopyright} 2018 American Society for Microbiology.",
year = "2018",
month = feb,
day = "1",
doi = "10.1128/JVI.01246-17",
language = "English (US)",
volume = "92",
journal = "Journal of virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",
}