Induction of protective immunity against severe acute respiratory syndrome coronavirus (SARS-CoV) infection using highly attenuated recombinant vaccinia virus DIs

使用高度减毒重组痘苗病毒 DI 诱导针对严重急性呼吸综合征冠状病毒 (SARS-CoV) 感染的保护性免疫

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作者:Koji Ishii, Hideki Hasegawa, Noriyo Nagata, Tetsuya Mizutani, Shigeru Morikawa, Tetsuro Suzuki, Fumihiro Taguchi, Masato Tashiro, Toshitada Takemori, Tatsuo Miyamura, Yasuko Tsunetsugu-Yokota

Abstract

SARS-coronavirus (SARS-CoV) has recently been identified as the causative agent of SARS. We constructed a series of recombinant DIs (rDIs), a highly attenuated vaccinia strain, expressing a gene encoding four structural proteins (E, M, N and S) of SARS-CoV individually or simultaneously. These rDIs elicited SARS-CoV-specific serum IgG antibody and T-cell responses in vaccinated mice following intranasal or subcutaneous administration. Mice that were subcutaneously vaccinated with rDIs expressing S protein with or without other structural proteins induced a high level of serum neutralizing IgG antibodies and demonstrated marked protective immunity against SARS-CoV challenge in the absence of a mucosal IgA response. These results indicate that the potent immune response elicited by subcutaneous injection of rDIs containing S is able to control mucosal infection by SARS-CoV. Thus, replication-deficient DIs constructs hold promise for the development of a safe and potent SARS vaccine.

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