The Toxicity Evaluation of Recombinant Replicating Vaccinia Virus Vaccine in BALB/c Mice

摘要

To evaluate the preclinical safety of recombinant replicating vaccinia virus-based HIV vaccines(rVW) in BALB/c mice. The study was composed of groups 1,2,3,4, wherein the groups 1 and 2 received only one priming immunization and the groups 3, 4 received prime-boost immunizations at a 6-week interval. The dose given was 50μl/skin of back/2 dosing point by intradennal injection approximately 2.2×106 PFU. Cellular responses were evaluated in spleenocytes after restimulation on the following basis: detection of IFN-γproducing CD8+-positive T cells, and CD4+/CD8+T cells ratio by FACS assay. Humoral responses were evaluated in serum samples on the basis of specific and-rVVV antibodies. A real-time quantitative PCR was employed for detection of biodistribution of rVVV in tissues and organs. The results showed that there were no significant toxic effects and damages to major organs in control and rVVV-treated animals. The results of FACS analysis assay for the group 4 that received primeboost immunization showed cellular immune responses, as indicated by high IFN-γproduction by CD8+-positive T cells. There was no significant change for the CD4 V CD8 ' T cells ratio in control and rVVV-treated animal. Immunogenicity of rVW given with primeboost doses was stronger than that of rVW given with a single priming dose in BALB/c mice. Following intradennal injection of rVW in mice, all tissues were Q-PCR-negative on Day 35 after dosing. The study showed that there were no significant toxic effects and the rVVV could induce both humoral and cellular immune responses in BALB/c mice.