Production and immunogenicity of chimeric virus-like particles containing the spike glycoprotein of infectious bronchitis virus

Lv, Lishan; Li, Xiaoming; Liu, Genmei; Li, Ran; Liu, Qiliang; Shen, Huifang; Wang, Wei; Xue, Chunyi; Cao, Yongchang

In this study, we investigated whether chimeric VLPs expressing IBV S1 protein on their surfaces could be generated in sf9 cells. The results showed that chimeric VLPs could be assembled by co-expressing fusion protein NA/S1 and influenza virus M1 protein. We also provided evidence demonstrating that chimeric VLPs were immunogenic and induced S1-specific antibody responses at a higher level than the inactivated H120 viruses. Furthermore, chimeric VLPs could induce significantly higher cellular immune-responses than the inactivated H120 viruses. IBV has an enormous economic impact on commercial poultry by causing highly contagious disease in chickens of all ages. Vaccination has been used to control IB for over half a century. Although inactivated and attenuated virus vaccines have contributed immensely to control of IB, they have some drawbacks. For example, attenuated virus vaccines pose a potential hazard of propagation of the virus via embryonated chicken eggs and therefore the risk of spreading the virus and generation of a stronger form. Despite this risk, inactivated virus vaccines are commonly used in combination with attenuated virus vaccines because they cannot induce a high level of S1-specific antibodies [10, 16, 21, 25] . Chimeric VLP is a promising development in the field of VLP research. For example, Newcastle disease VLPs contain respiratory syncytial virus proteins [26] , while membrane-anchored flagellin were incorporated into influenza VLPs [6] . In the present study, we demonstrated that fusion protein could successfully assemble and bud with influenza M1 to form chimeric VLPs, and that chimeric VLPs were similar to previously reported influenza VLPs. Accordingly, the results presented herein provide an additional example supporting the feasibility of generating chimeric VLPs [1] . This study demonstrated that the chimeric VLPs induced robust humoral responses with an obviously higher level than inactivated H120 viruses in both mice and chickens (p ＞ 0.05). In addition, a higher level of IL-4 was detected in the VLPs group than in the inactivated H120 group (p ＜ 0.05). Although the mechanism by which the chimeric VLPS elicited significantly higher IL-4 production than the inactivated H120 viruses is not clear. Furthermore, chimeric VLPs induced significantly higher neutralizing antibody titers than inactivated IBV viruses.