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Dengue viruses cluster antigenically but not as discrete serotypes.



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Katzelnick, Leah C 
Fonville, Judith M 
Gromowski, Gregory D 
Bustos Arriaga, Jose 
Green, Angela 


The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV.



Animals, Antibodies, Neutralizing, Antibodies, Viral, Antigens, Viral, Chlorocebus aethiops, Dengue Vaccines, Dengue Virus, Evolution, Molecular, Humans, Immune Sera, Phylogeny, Serogroup, Serotyping, Vaccination, Viral Envelope Proteins

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American Association for the Advancement of Science (AAAS)
Medical Research Council (MR/K021885/1)
Office of the Director (DP1OD000490)
National Institutes of Health (NIH) (via Mount Sinai School of Medicine (MSSM)) (HHSN272201400008C)
Wellcome Trust (100891/Z/13/Z)
European Commission (223498)
European Commission (278976)
This research was supported in part by the Intramural Research Program of the US NIH, National Institute of Allergy and Infectious Diseases, European Union (EU) FP7 programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science Program (HFSP) program grant P0050/2008, the NIH Director’s Pioneer Award DP1-OD000490-01, the FIRST program from the Bill and Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (E.H.). The antigenic cartography toolkit was in part supported by NIAID-NIH Centers of Excellence for Influenza Research and Surveillance contracts HHSN266200700010C and HHSN272201400008C for use on influenza virus. L.C.K. was supported by the Gates Cambridge Scholarship and the NIH Oxford Cambridge Scholars Program. J.M.F. was supported by an MRC Fellowship (MR/K021885/1) and a Junior Research Fellowship from Homerton College Cambridge. E.C.H. was supported by an NHMRC Australia Fellowship. N.V. and R.B.T were supported by NIH contract HHSN272201000040I/HHSN27200004/D04.