Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models

Okada, Masaji; Okuno, Yoshinobu; Hashimoto, Satomi; Kita, Yoko; Kanamaru, Noriko; Nishida, Yasuko; Tsunai, Yoshie; Inoue, Ruriko; Nakatani, Hitoshi; Fukamizu, Reiko; Namie, Yumi; Yamada, Junko; Takao, Kyoko; Asai, Ritsuko; Asaki, Ryoko; Kase, Tetsuo; Takemoto, Yuji; Yoshida, Shigeto; Peiris, J.S.M.; Chen, Pei-Jer; Yamamoto, Naoki; Nomura, Tatsuji; Ishida, Isao; Morikawa, Shigeru; Tashiro, Masato; Sakatani, Mitsunori

We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor γ-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines.