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- Title
Dengue-1 Envelope Protein Domain III along with PELC and CpG Oligodeoxynucleotides Synergistically Enhances Immune Responses.
- Authors
Chiang, Chen-Yi; Huang, Ming-Hsi; Hsieh, Chun-Hsiang; Chen, Mei-Yu; Liu, Hsueh-Hung; Tsai, Jy-Ping; Li, Yi-Shiuan; Chang, Ching-Yun; Liu, Shih-Jen; Chong, Pele; Leng, Chih-Hsiang; Chen, Hsin-Wei
- Abstract
The major weaknesses of subunit vaccines are their low immunogenicity and poor efficacy. Adjuvants can help to overcome some of these inherent defects with subunit vaccines. Here, we evaluated the efficacy of the newly developed water-in-oil-in-water multiphase emulsion system, termed PELC, in potentiating the protective capacity of dengue-1 envelope protein domain III. Unlike aluminum phosphate, dengue-1 envelope protein domain III formulated with PELC plus CpG oligodeoxynucleotides induced neutralizing antibodies against dengue-1 virus and increased the splenocyte secretion of IFN-γ after in vitro re-stimulation. The induced antibodies contained both the IgG1 and IgG2a subclasses. A rapid anamnestic neutralizing antibody response against a live dengue virus challenge was elicited at week 26 after the first immunization. These results demonstrate that PELC plus CpG oligodeoxynucleotides broaden the dengue-1 envelope protein domain III-specific immune responses. PELC plus CpG oligodeoxynucleotides is a promising adjuvant for recombinant protein based vaccination against dengue virus. Author Summary: Dengue is a mosquito-borne disease. Infection of dengue virus can cause clinical manifestations ranging from self-limiting dengue fever to potentially life-threatening dengue hemorrhagic fever or dengue shock syndrome. In recent years, dengue has spread to most tropical and subtropical areas, making it a global health concern. Specific approaches for dengue therapy do not exist; the development of a dengue vaccine would represent a major advance in the control of the disease. Currently, no licensed dengue vaccine is available. Subunit vaccines provide a great safety strategy for developing dengue vaccine. However, the major weaknesses of subunit vaccines are low immunogenicity and poor efficacy. Here we employed dengue-1 envelope protein domain III as a model vaccine candidate and described a newly developed water-in-oil-in water multiphase emulsion system to overcome the inherent defect of subunit vaccines. We showed that emulsification of dengue-1 envelope protein domain III and CpG oligodeoxynucleotides synergistically broadened immune responses and potentiated the protective capacity of dengue-1 envelope protein domain III. These results provide valuable information for development of recombinant protein based vaccination against dengue virus and future clinical studies.
- Subjects
DENGUE hemorrhagic fever; CPG nucleotides; PROTEIN domains; DENGUE viruses; IMMUNE response; DENGUE
- Publication
PLoS Neglected Tropical Diseases, 2012, Vol 6, Issue 5, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0001645