Jiang B, Estes M K, Barone C, Barniak V, O'Neal C M, Ottaiano A, Madore H P, Conner M E
Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY 10965, USA.
Vaccine. 1999 Feb 26;17(7-8):1005-13. doi: 10.1016/s0264-410x(98)00317-x.
Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3 serotype specificity were produced in insect cells coinfected with recombinant baculoviruses expressing single rotavirus genes. The VLPs were purified and subsequently evaluated for immunogenicity and protection in the adult mouse model of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice were examined for serum and fecal antibody responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine ECwt rotavirus was assessed by comparing the antigen shed in stool of the VLP-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented antibody responses were further characterized by equivalent IgG1 and IgG2a titers in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in QS-21 induced partial protection (88%) against oral challenge with the heterotypic ECwt virus, whereas G3 VLPs in QS-21 induced complete protection (100%). In contrast, G1 VLPs when formulated with AlOH induced a predominant Th2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody responses to rotavirus VLPs and the protective efficacy against rotavirus infections. These data have important implications for the development of parenteral vaccines to ameliorate rotavirus disease.
通过与表达单个轮状病毒基因的重组杆状病毒共感染昆虫细胞，产生了由G1或G3血清型特异性的轮状病毒VP2、VP6和VP7组成的病毒样颗粒（VLP）。对这些VLP进行纯化，随后在轮状病毒感染的成年小鼠模型中评估其免疫原性和保护作用。用含有皂树皂苷（QS-21）配制的G1 VLP或吸附于氢氧化铝（AlOH）的G1 VLP，或单独的G1 VLP对小鼠进行两次肌肉注射免疫。G3 VLP、G1加G3 VLP、用QS-21配制的灭活SA11病毒粒子或佐剂作为对照进行类似接种。通过ELISA或微量中和试验检测小鼠的血清和粪便抗体反应。通过比较VLP疫苗接种小鼠粪便中排出的抗原与佐剂免疫小鼠的抗原，评估VLP疫苗制剂对G3鼠ECwt轮状病毒口服攻击的保护效果。与AlOH中的G1 VLP或单独的G1 VLP相比，QS-21中的G1 VLP诱导的血清和肠道抗体滴度显著更高。QS-21还增强了对G3 VLP的血清和粪便抗体反应。这些QS-21增强的抗体反应的进一步特征是血清中IgG1和IgG2a滴度相当，表明QS-21中的G1或G3 VLP诱导了平衡的Th1/Th2反应。QS-21中的G1 VLP对异型ECwt病毒口服攻击诱导了部分保护（88%），而QS-21中的G3 VLP诱导了完全保护（100%）。相比之下，用AlOH配制的G1 VLP诱导了主要的Th2反应，并且不能保护（1%）小鼠免受病毒攻击。我们的结果表明，所用佐剂的类型明显影响对轮状病毒VLP的抗体反应以及对轮状病毒感染的保护效果。这些数据对开发用于改善轮状病毒疾病的肠道外疫苗具有重要意义。
