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首页> 外文期刊>Vaccine >Immunogenicity and protective efficacy of rotavirus 2/6-virus-like particles produced by a dual baculovirus expression vector and administered intramuscularly, intranasally, or orally to mice
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Immunogenicity and protective efficacy of rotavirus 2/6-virus-like particles produced by a dual baculovirus expression vector and administered intramuscularly, intranasally, or orally to mice

机译：由双杆状病毒表达载体产生并经肌肉，鼻内或口服给予小鼠的轮状病毒2 / 6-病毒样颗粒的免疫原性和保护功效

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Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. Rotavirus VLPs composed of simian SA11 strain VP2 and VP6 proteins (homologous 2/6-VLPs) were produced by cloning the rotavirus simian SA11 genes 2 and 6 into a single baculovirus transfer vector (pAcAB4). The overall yield of homologous 2/6-VLPs produced with the dual recombinant baculovirus was at least 30-fold higher than that of VLPs composed of bovine RF strain VP2 and simian SA11 strain VP6 (heterologous 2/6-VLPs), produced with single recombinant baculoviruses. Adult mice were immunized intramuscularly twice with various doses of homologous or heterologous 2/6-VLPs in QS-21, orally with or without cholera toxin (CT), or intranasally with mutant Escherichia coli heat-labile enterotoxin (LT-R192G). Both homologous and heterologous 2/6-VLPs were immunogenic and induced protection from challenge, with those administered parenterally or intranasally affording the highest mean protection from challenge. The 2/6-VLPs did not induce serum neutralizing antibody (N-Ab) responses, but these VLPs primed for a broad heterotypic N-Ab response, which was elicited after rotavirus challenge. Heterotypic N-Ab responses were not observed in 2/6-VLP vaccinated mice that were greater than or equal to94% protected from challenge. After challenge, control mice immunized with adjuvant alone developed only homotypic serum N-Ab responses. Similar results were obtained after challenge of rabbits immunized parenterally or intranasally with heterologous 2/6-VLPs. These results suggest that 2/6-VLPs prime the immune system to enhance the production of heterotypic N-Ab responses, but the induction of heterotypic N-Abs requires that virus replication occurs after challenge. The use of 2/6-VLPs expressed from a single recombinant baculovirus simplifies production and would reduce the cost of a VLP-based vaccine.
机译：病毒样颗粒（VLP）正在作为轮状病毒候选疫苗进行评估。通过将轮状病毒猿猴SA11基因2和6克隆到单个杆状病毒转移载体（pAcAB4）中，生产出由猿猴SA11株VP2和VP6蛋白（同源2 / 6-VLP）组成的轮状病毒VLP。用双重重组杆状病毒产生的同源2 / 6-VLP的总产量比由单株产生的牛RF株VP2和猿猴SA11株VP6的VLP（异源2 / 6-VLP）至少高30倍。重组杆状病毒。用QS-21中不同剂量的同源或异源2 / 6-VLP肌肉注射成年小鼠两次，口服或不口服霍乱毒素（CT），或经鼻内用突变型大肠杆菌不耐热肠毒素（LT-R192G）免疫。同源和异源2 / 6-VLPs都是免疫原性的，并且可以诱导免受攻击，肠胃外或鼻内施用的那些均提供最高的抗攻击平均保护。 2 / 6-VLP不会诱导血清中和抗体（N-Ab）反应，但这些VLP引发了广泛的异型N-Ab反应，这是在轮状病毒攻击后引发的。在2 / 6-VLP疫苗接种的小鼠中未观察到异型N-Ab应答，该应答大于或等于94％免受攻击。攻击后，仅用佐剂免疫的对照小鼠仅出现同型血清N-Ab反应。用异源2 / 6-VLP肠胃外或鼻内免疫兔子后，也获得了相似的结果。这些结果表明，2 / 6-VLPs引发免疫系统以增强异型N-Ab反应的产生，但是异型N-Abs的诱导需要在攻击后发生病毒复制。由单个重组杆状病毒表达的2 / 6-VLP的使用可简化生产，并降低基于VLP的疫苗的成本。

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