Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles

Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 o r G3 serotype specificity were produced in insect cells coinfected with rec ombinant baculoviruses expressing single rotavirus genes. The VLPs were pur ified and subsequently evaluated for immunogenicity and protection in the a dult mouse model of rotavirus infection. Mice were vaccinated twice intramu scularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbe d 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 si milarly inoculated as controls. Mice were examined for serum and fecal anti body responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine E C,, rotavirus was assessed by comparing the antigen shed in stool of the VL P-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 V LPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibod y responses to G3 VLPs. These QS-21-augmented antibody responses were furth er characterized by equivalent IgG1 and IgG2a titers in sera, suggesting th at G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in Q S-21 induced partial protection (88%) against oral challenge with the heter otypic EC,, virus, whereas G3 VLPs in QS-21 induced complete protection (10 0%). In contrast, G1 VLPs when formulated with AlOH induced a predominant T h2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody r esponses to rotavirus VLPs and the protective efficacy against rotavirus in fections. These data have important implications for the development of par enteral vaccines to ameliorate rotavirus disease. (C) 1999 Elsevier Science Ltd. All rights reserved.