Journal
SCIENCE
Volume 349, Issue 6254, Pages 1338-1343Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac5017
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Funding
- Intramural Research Program of the U.S. NIH
- National Institute of Allergy and Infectious Diseases (NIAID)
- European Union (EU) [223498, 278976]
- Human Frontier Science Program (HFSP) program grant [P0050/2008]
- NIH Director's Pioneer Award [DP1-OD000490-01]
- FIRST program from the Bill and Melinda Gates Foundation
- Instituto Carlos Slim de la Salud
- NIAID-NIH Centers of Excellence for Influenza Research and Surveillance [HHSN266200700010C, HHSN272201400008C]
- Gates Cambridge Scholarship
- NIH Oxford Cambridge Scholars Program
- Medical Research Council Fellowship [MR/K021885/1]
- Junior Research Fellowship from Homerton College Cambridge
- National Health and Medical Research Council Australia Fellowship
- NIH [HHSN272201000040I/HHSN27200004/D04]
- GSK Pharma
- GSK Vaccines
- Merck
- MRC [MR/K021885/1] Funding Source: UKRI
- Medical Research Council [MR/K021885/1] Funding Source: researchfish
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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.
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