title: Role of humoral versus cellular responses induced by a protective dengue vaccine candidate.
abstract: With 2.5 billion people at risk, dengue is a major emerging disease threat and an escalating public health problem worldwide. Dengue virus causes disease ranging from a self-limiting febrile illness (dengue fever) to the potentially fatal dengue hemorrhagic fever/dengue shock syndrome. Severe dengue disease is associated with sub-protective levels of antibody, which exacerbate disease upon re-infection. A dengue vaccine should generate protective immunity without increasing severity of disease. To date, the determinants of vaccine-mediated protection against dengue remain unclear, and additional correlates of protection are urgently needed. Here, mice were immunized with viral replicon particles expressing the dengue envelope protein ectodomain to assess the relative contribution of humoral versus cellular immunity to protection. Vaccination with viral replicon particles provided robust protection against dengue challenge. Vaccine-induced humoral responses had the potential to either protect from or exacerbate dengue disease upon challenge, whereas cellular immune responses were beneficial. This study explores the immunological basis of protection induced by a dengue vaccine and suggests that a safe and efficient vaccine against dengue should trigger both arms of the immune system.
authors.affiliation: La Jolla Institute for Allergy & Immunology, La Jolla, California, United States of America.
authors.forename: Raphaël M
authors.initials: RM
authors.lastname: Zellweger
authors.forename: Robyn
authors.initials: R
authors.lastname: Miller
authors.forename: William E
authors.initials: WE
authors.lastname: Eddy
authors.forename: Laura J
authors.initials: LJ
authors.lastname: White
authors.forename: Robert E
authors.initials: RE
authors.lastname: Johnston
authors.forename: Sujan
authors.initials: S
authors.lastname: Shresta
mesh_terms: D000818:Animals; D003715:Dengue / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology / Q000494:pharmacology*; D003716:Dengue Virus / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D051379:Mice; D014611:Vaccination
chemical_list: D053059:Dengue Vaccines