Construction And Evaluation Of Novel Recombinant Vesicular Stomatitis Virus In Animals

Presently, attenuated and inactivated pathogens are commonly applied for developingvaccines. Many attenuated viruses has been used to express foreign antigens which canstimulate efficient and comprehensive immunue responses in vivo,and can be a promisingmethod for vaccine development.Vesicular stomatitis virus (VSV) is an excellent viral vector. In vivo studies indicated thatrecombinant VSV can stimulate both humoral immunity and cellular immunity, which inducecomprehensive andLasting protection for animals. However, there still exist toxicities withrecombinant VSVs in animals. Inoculated with high doses of VSV, neurotoxicity includinghindLimg paralysis appeared in BALB/c mice. Therefore, VSV still need to be attenuated dueto its toxicities in animals.Protein M is an important virulent factor of VSV, which involved in viral pathogenesis.Recent studies have shown that there is a mutant of VSV whose M51mutated to R51, whichwas much less pathogenic than wild-type VSV. But there is a deficiency that is all of data aboutimportance of protein for VSV’s pathogenesis which come from mice.Swine is one of natural hosts of VSV, however, of the role of M protein in viral pathogenesishas not been identifiedwith wild-type VSV as the control, pathogenicity and immunogenicity ofVSVΔM51has been studied, which has indicated that Symptoms of animals which wereinoculated with VSVΔM51were relieved significantly. According to neutralizing antibody test,VSVΔM51can stimulate natural host to generate immune responses, therefore, it can be apotential vaccine vector for pigs.Since VSVΔM51still has pathogenesis, it is the target to construct attenuated recombinantVSV. In our study, an attenuated VSV with triple amino acids mutated has been constructed,which included M51deletion, V221F, S226R. Based on in vitro and in vivo characterizations,VSV-MT indicated significant attenuations in comparison with wild-type VSV and that with onlyM51deletion.To test protective immune responses stimulated by VSV-MT, BALB/c mice were inoculatedwith VSV-MT at different doses.21days post immunization, immunized animals werechallenged with high-dosed wild-type VSV. Based on body weightLosses and neutralization antibody detections in challenged mice, it showed that VSV-MT can stimulate potent protectionin animals.