TY - JOUR
T1 - Challenges for the formulation of a universal vaccine against dengue
AU - Chokephaibulkit, Kulkanya
AU - Perng, Guey Chuen
N1 - Funding Information:
We would like to thank the clinical staffs at the Division of Infectious Diseases in the Department of Pediatrics at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. The authors appreciate the kindness of Professor Aftab A Ansari and Kristina B Clark, Department of Pathology and Laboratory Medicine, Emory University School Medicine, for reading and editing the manuscript. The authors also would like to thank you Dr Sansanee Noisakran, Medical Biotechnology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok, Thailand, and Miss Hui-Mien Hsiao, Department of pathology and Laboratory Medicine, Emory University School of Medicine, for the assisting in the antibody neutralization assays. This study was supported in part by Thailand Research Fund for Senior Research Scholar, and by a startup grant from the National Science Council (NSC99-2321-B006-008) with the Center of Infectious Disease and Signaling Research, NCKU, Taiwan.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/8
Y1 - 2013/8
N2 - Dengue is rapidly becoming a disease of an escalating global public health concern. The disease is a vector-borne disease, transmitted by the bite of an Aedes spp. mosquito. Dynamic clinical manifestations, ranging from asymptomatic, flu-like febrile illness, dengue fever (DF) to dengue hemorrhagic fever (DHF) with or without dengue shock syndrome (DSS), make the disease one of the most challenging to diagnose and treat. DF is a self-limited illness, while DHF/DSS, characterized by plasma leakage resulting from an increased vascular permeability, can have severe consequences, including death. The pathogenesis of dengue virus infection remains poorly understood, mainly due to the lack of a suitable animal model that can recapitulate the cardinal features of human dengue diseases. Currently, there is no specific treatment or antiviral therapy available for dengue virus infection and supportive care with vigilant monitoring is the principle course of treatment. Since vector control programs have been largely unsuccessful in preventing outbreaks, vaccination seems to be the most viable option for prevention. There are four dengue viral serotypes and each one of them is capable of causing severe dengue. Although immunity induced by infection by one serotype is effective in protection against the homologous viral serotype, it only has a transient protective effect against infection with the other three serotypes. The meager cross protective immunity generated wanes over time and may even induce a harmful effect at the time of subsequent secondary infection. Thus, it is imperative to have a vaccine that can elicit equal and long-lasting immunity to all four serotypes simultaneously. Numerous tetravalent vaccines are currently either in the pipeline for clinical trials or under development. For those frontrunner tetravalent vaccines in clinical trials, despite good safety and immunogenicity profiles registered, issues such as imbalanced immune responses between serotypes and questions with regard to whether the optimum formulation have been identified remain unresolved. This review centers on these issues and offers strategies that may improve the tetravalent vaccine formulation.
AB - Dengue is rapidly becoming a disease of an escalating global public health concern. The disease is a vector-borne disease, transmitted by the bite of an Aedes spp. mosquito. Dynamic clinical manifestations, ranging from asymptomatic, flu-like febrile illness, dengue fever (DF) to dengue hemorrhagic fever (DHF) with or without dengue shock syndrome (DSS), make the disease one of the most challenging to diagnose and treat. DF is a self-limited illness, while DHF/DSS, characterized by plasma leakage resulting from an increased vascular permeability, can have severe consequences, including death. The pathogenesis of dengue virus infection remains poorly understood, mainly due to the lack of a suitable animal model that can recapitulate the cardinal features of human dengue diseases. Currently, there is no specific treatment or antiviral therapy available for dengue virus infection and supportive care with vigilant monitoring is the principle course of treatment. Since vector control programs have been largely unsuccessful in preventing outbreaks, vaccination seems to be the most viable option for prevention. There are four dengue viral serotypes and each one of them is capable of causing severe dengue. Although immunity induced by infection by one serotype is effective in protection against the homologous viral serotype, it only has a transient protective effect against infection with the other three serotypes. The meager cross protective immunity generated wanes over time and may even induce a harmful effect at the time of subsequent secondary infection. Thus, it is imperative to have a vaccine that can elicit equal and long-lasting immunity to all four serotypes simultaneously. Numerous tetravalent vaccines are currently either in the pipeline for clinical trials or under development. For those frontrunner tetravalent vaccines in clinical trials, despite good safety and immunogenicity profiles registered, issues such as imbalanced immune responses between serotypes and questions with regard to whether the optimum formulation have been identified remain unresolved. This review centers on these issues and offers strategies that may improve the tetravalent vaccine formulation.
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U2 - 10.1177/1535370212473703
DO - 10.1177/1535370212473703
M3 - Review article
C2 - 23856907
AN - SCOPUS:84881606622
VL - 238
SP - 566
EP - 578
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
SN - 1535-3702
IS - 5
ER -