Generation of primary antigen-specific immune response to SFV-based vaccine in a trimera model
Bing Ni, China Bo Zhu: Cancer Center of PLA, Rod Bremner: Cellular and Molecular Division, Zhihua Lin, Liyun Zou, Zhengcai Jia, Canada
AIM: In this study, we have employed humanized BALB/c mice (termed trimera mice) to characterize the antitumor immunity elicited by the recombinant Semliki Forest virus (SFV) encoding the MAGE-3 antigen, and compared with that induced by the plasmid DNA vaccine. EXPERIMENTAL DESIGN: Trimera mice were established by adoptive transfer of human peripheral blood mononuclear cells (PBMC) into lethally irradiated BALB/c mice, which is radio-protected with bone marrow from donors with severe combined immune deficiency. Primary MAGE-3-specific antibody response and cytotoxic T lymphocyte (CTL) response were demonstrated respectively by ELISA and 4h 51Cr-release assay, following the delivery of recombinant SFV or control plasmid DNA into trimera mice. RESULTS: In accordance with other reports, our results showed that engraftment of PBMC in peritoneum was above 80%, whereas that in blood and spleen were 10% and above 50%, respectively. Moreover, the results showed that SFV-mediated MAGE-3 vaccination could elicit MAGE-3-specific Ab and CTL response in the trimera mouse model. Furthermore, we demonstrated that SFV-mediated MAGE-3 vaccination was more potent than plasmid DNA vaccination, such as pCI-MAGE-3, in the induction of primary antitumor immune response. CONCLUSIONS: The ability of recombinant SFV to elicit specific, protective immune responses in humanized animal models suggests that rSFV may be used as a vaccine vehicle in human.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 1091 (Vaccine trials).