DEVELOPMENT OF MULTI-EPITOPE VACCINE AGAINST DENGUE VIRUS FOR INDONESIAN POPULATION USING THE APPROACH OF REVERSE VACCINOLOGY
Infection of Dengue Virus becomes one global health problem due to the high number of Dengue Fever in many subtropical and tropical countries, including Indonesia. Although one commercial DENV vaccine has been available, the vaccine is still not adequate to prevent DENV infection in broad population...
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| Format: | Theses |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/57741 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Infection of Dengue Virus becomes one global health problem due to the high number of Dengue Fever in many subtropical and tropical countries, including Indonesia. Although one commercial DENV vaccine has been available, the vaccine is still not adequate to prevent DENV infection in broad populations. Unlike the conventional method, reverse vaccinology can develop new vaccine candidates quickly, safely, and effectively. The structural proteins of DENV can be used as a potential antigen target because they play a crucial role in early infection and are associated with antibody-dependent enhancement. In this research, we performed reverse vaccinology to construct multi-epitope vaccine-derived DENV structural proteins to induce a protective immune response against four serotypes of DENV. The T and B lymphocyte epitopes were predicted from the consensus sequence of the DENV structural proteins and selected based on their physicochemical and biological properties. The selected epitopes were linked to an adjuvant using linkers to construct a multi-epitope vaccine candidate. The secondary and tertiary structure of the vaccine candidate was predicted. Then, the tertiary structure of the vaccine candidate was validated. The molecular docking analysis between the vaccine candidate and the receptor of TLR4 and TLR7 was performed. Next, the codon optimization, in-silico cloning of the vaccine candidate into pET28a (+) was performed. We acquired one vaccine candidate consisting of adjuvant cholera toxin subunit B, three epitopes of cytotoxic T lymphocyte, and one epitope of helper T lymphocyte-derived from DENV envelope protein. The vaccine candidate had a good quality result with a Z-score of -5.62, ERRAT-score of 69.33, and Ramachandran favored region of 91.8%. In addition, we found the vaccine candidates predicted to bind spontaneously to TLR-4 and TLR7 with the binding affinity of -9 and -7.5 kcal/mol and expected to express well in Escherichia coli strain K12 with CAI of 0.96 and %GC of 44.05. However, advance in vitro and in vivo validation studies are still required to validate the characteristics of the vaccine candidate.
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