Role of humoral versus cellular responses induced by a protective dengue vaccine candidate.
Role of humoral versus cellular responses induced by a protective dengue vaccine candidate.
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DOI：
10.1371/journal.ppat.1003723
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发表时间：
2013-10
期刊：
影响因子：
6.7
通讯作者：
Shresta S
中科院分区：
文献类型：
--
作者：
Zellweger RM;Miller R;Eddy WE;White LJ;Johnston RE;Shresta S
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. Dengue virus is an escalating public health threat for over 2.5 billion people worldwide. The disease caused by dengue virus ranges from mild (dengue fever) to lethal (dengue hemorrhagic fever, dengue shock syndrome). To date, there is no cure or vaccine for dengue. One of the challenges to developing a safe and efficient dengue vaccine is that antibodies, usually induced by vaccines to protect the host from re-infection, can increase the severity of dengue disease if they are not present in sufficient amounts to neutralize the virus. An efficient vaccine is urgently needed to slow down the progression of dengue disease, but little is known about the way the immune system protects the body against dengue re-infection. Using a protective vaccine candidate for dengue, the present study evaluates in mice the relative contribution of T cells and antibodies to protection against dengue. We show that the antibody component of an immune response that is overall protective had the ability, when isolated from the other components of the immune system, to either decrease or increase viral burden, whereas T cells reduced viral burden in all situations tested. Our results suggest that vaccine development efforts should focus on approaches that induce both T cell and antibody responses against dengue virus.
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