DESAIN VEKTOR ADENOVIRUS 5 DENGAN URUTAN HYPERVARIABLE REGION (HVR) HEXON ADENOVIRUS 26

• Main Author: Firdaus Syuaib, Afina
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/56635
• Institution: Institut Teknologi Bandung

Adenovirus type 5 (Ad5) is one of the popular vaccine vectors, including the COVID-19 vaccine. Preexisting immunity to Ad5 may suppress the immunogenicity and efficacy of adenovirus vector vaccine. The neutralizing antibodies are directed specifically toward seven hypervariable regions (HVR) of hexon proteins located on the outer surface of the capsid. This study aims to construct an Ad5 vector that may circumvent anti-Ad5 immunity by designing a chimera Ad5 vector with the sequence of HVR Ad26 (Ad5HVR26). Substitution of the Ad5 HVR DNA sequence may affect the alternative splicing process of adenovirus mRNA, which then influence the protein product. The splice site prediction of Ad5HVR26 chimera vector was found at HVR5, 6, and 7. The codon change on the splice site is performed to decrease the possibility of incorrect splicing, while retaining the original amino acid sequence. The HVR substitution in chimera vector Ad5HVR26 may also affect the interaction of hexon in the capsid. The HVR2 and HVR4 hexon proteins individually interact with other hexon proteins and IX protein. Based on the splice site prediction and amino acid interaction analyses, two designs of the Ad5HVR26 chimera vector are proposed in this research. The first design is the Ad5 chimera vector with complete substitution of HVR hexon by Ad26 sequence, with codon modification on the splice site. The second design in Ad5HVR26 chimera vector without the HVR2 and HVR4 substitution to maintain the hexon protein interaction with the capsid proteins.