Jose Luis Slon CamposJuthathip MongkolsapayaGavin R. ScreatonUniversity of OxfordFaculty of Medicine, Siriraj Hospital, Mahidol UniversityNuffield Department of Clinical Medicine2019-08-232019-08-232018-11-01Nature Immunology. Vol.19, No.11 (2018), 1189-119815292916152929082-s2.0-85055206461https://repository.li.mahidol.ac.th/handle/20.500.14594/45947© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc. Arthropod-borne flaviviruses are important human pathogens that cause a diverse range of clinical conditions, including severe hemorrhagic syndromes, neurological complications and congenital malformations. Consequently, there is an urgent need to develop safe and effective vaccines, a process requiring better understanding of the immunological mechanisms involved during infection. Decades of research suggest a paradoxical role of the immune response against flaviviruses: although the immune response is crucial for the control, clearance and prevention of infection, poor clinical outcomes are commonly associated with virus-specific immunity and immunopathogenesis. This relationship is further complicated by the high homology among viruses and the implication of cross-reactive immune responses in protection and pathogenesis. This Review examines the dual role of the adaptive immune response against flaviviruses, particularly emphasizing the most recent findings regarding cross-reactive T cell and antibody responses, and the effects that these concepts have on vaccine-development endeavors.Mahidol UniversityImmunology and MicrobiologyMedicineReviewSCOPUS10.1038/s41590-018-0210-3