title: Dengue viruses cluster antigenically but not as discrete serotypes.
abstract: 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.
authors.affiliation: Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Katzelnick
authors.affiliation: Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Fonville
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gromowski
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Bustos Arriaga
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Green
authors.affiliation: Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: James
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Lau
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Magelda
authors.initials: M
authors.lastname: Montoya
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: VanBlargan
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Russell
authors.affiliation: Department of Medical Research, Ziwaka Road, Yangon, Myanmar.
authors.forename: Hlaing Myat
authors.initials: HM
authors.lastname: Thu
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Pierson
authors.affiliation: Institut Pasteur in Cambodia, Réseau International des Instituts Pasteur, Phnom Penh 12201, Cambodia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4001, Australia. Australian Army Malaria Institute, Brisbane 4051, Australia.
authors.forename: John G
authors.initials: JG
authors.lastname: Aaskov
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan 00971, Puerto Rico.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Muñoz-Jordán
authors.affiliation: Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
authors.affiliation: Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Tesh
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands.
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.affiliation: Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Durbin
authors.affiliation: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, UK. Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney 2006, Australia.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
authors.affiliation: Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands. djs200@cam.ac.uk.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D002522:Chlorocebus aethiops; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D010802:Phylogeny; D065288:Serogroup; D012703:Serotyping; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; C084188:E protein, Dengue virus type 3; D007106:Immune Sera; D014759:Viral Envelope Proteins; C466981:glycoprotein E, dengue virus type 4; C072281:E protein TH Sman, Dengue virus