Trianti Irisa, Akeprathumchai Saengchai, Mekvichitsaeng Phenjun, Rachdawong Sansanalak, Poomputsa Kanokwan
Biotechnology Program, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, 49 Soi Thian Thale 25, Bang Khun Thian Chai Thale Road, Tha Kham, Bang Khun Thian, Bangkok, 10150, Thailand.
Pilot Plant Development and Training Institute, King Mongkut's University of Technology Thonburi, 49 Soi Thian Thale 25, Bang Khun Thian Chai Thale Road, Tha Kham, Bang Khun Thian, Bangkok, 10150, Thailand.
AMB Express. 2018 Oct 16;8(1):170. doi: 10.1186/s13568-018-0699-8.
Baculovirus is a promising vaccine deliver vector due to its biosafety profiles, gene transfer efficiency, ability to display small foreign antigens on its surface, strong adjuvant activities, etc. A dual vector for peptide antigens and a DNA vaccine delivery was constructed. In this vector, a tetrameric glycoprotein neuraminidase (NA) from influenza A virus (H5N1) serves as a baculovirus surface protein to improve baculovirus transduction efficiency and a partner for displaying the target peptide antigen. Nucleotides encoding target peptides could be fused to a full length NA gene, at the lower part of its head structure, integrated into Autographa californica multinucleopolyhedrovirus genome and expressed under the control of a White Spot Syndrome Virus IE-1 shuttle promoter. Angiotensin II (AngII) peptides, a potent vasoconstrictor that causes high blood pressure, was our target antigen. The recombinant NA-AngII pseudotyped baculovirus had the AngII peptides fused to the NA and displayed on its surface. In vitro studies revealed that this recombinant baculovirus successfully delivered AngII peptides, as DNA vaccine, into human HEK293A cells. A single subcutaneous injection of the recombinant NA-AngII pseudotyped baculovirus into moderately high blood pressure rats at 4 × 10 pfu/rat, stimulated anti-AngII antibody production and their systolic blood pressure (SBP) levels were found to have decreased. In addition, a single intranasal immunization at 8 × 10 pfu/rat, raised anti-AngII antibodies in a rat and its SBP was also reduced. The recombinant neuraminidase pseudotyped baculovirus is a potential vector for AngII peptide antigen and DNA vaccine for subcutaneous or intranasal immunization for treatment of hypertension.
杆状病毒因其生物安全性、基因转移效率、在其表面展示小的外源抗原的能力、强大的佐剂活性等,是一种很有前景的疫苗递送载体。构建了一种用于肽抗原和DNA疫苗递送的双载体。在该载体中,来自甲型流感病毒(H5N1)的四聚体糖蛋白神经氨酸酶(NA)作为杆状病毒表面蛋白,以提高杆状病毒转导效率,并作为展示靶肽抗原的伴侣。编码靶肽的核苷酸可融合到全长NA基因上,在其头部结构的下部,整合到苜蓿银纹夜蛾多核多角体病毒基因组中,并在白斑综合征病毒IE-1穿梭启动子的控制下表达。血管紧张素II(AngII)肽是一种导致高血压的强效血管收缩剂,是我们的靶抗原。重组NA-AngII假型杆状病毒使AngII肽与NA融合并展示在其表面。体外研究表明,这种重组杆状病毒成功地将作为DNA疫苗的AngII肽递送至人HEK293A细胞中。以4×10 pfu/只大鼠的剂量对中度高血压大鼠进行单次皮下注射重组NA-AngII假型杆状病毒,刺激了抗AngII抗体的产生,并且发现它们的收缩压(SBP)水平有所降低。此外,以8×10 pfu/只大鼠的剂量进行单次鼻内免疫,在一只大鼠中产生了抗AngII抗体,其SBP也降低了。重组神经氨酸酶假型杆状病毒是一种潜在的载体,可用于AngII肽抗原和DNA疫苗的皮下或鼻内免疫,用于治疗高血压。