Role of Humoral versus Cellular Responses Induced by a Protective Dengue Vaccine Candidate

PLoS Pathogens

Robert E. Johnston¹  Laura J. White¹  Robyn Miller²  William E. Eddy²  Raphaël M. Zellweger²  Sujan Shresta² 

[1] Global Vaccines Inc., Research Triangle Park, North Carolina, United States of America;La Jolla Institute for Allergy & Immunology, La Jolla, California, United States of America

关键词: T cells;    Cytotoxic T cells;    Mouse models;    B cells;    Immune response;    Viral load;    Vaccination;    immunization;    Vaccines;   

DOI  :  10.1371/journal.ppat.1003723

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY