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Clinical and Vaccine Immunology, August 2007, p. 990-997, Vol. 14, No. 8
1071-412X/07/$08.00+0 doi:10.1128/CVI.00076-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Type IVB Pilus Operon Promoter Controlling Expression of the Severe Acute Respiratory Syndrome-Associated Coronavirus Nucleocapsid Gene in Salmonella enterica Serovar Typhi Elicits Full Immune Response by Intranasal Vaccination
Fengling Luo,1,
Yong Feng,1,2,
Min Liu,1
Pingfei Li,1
Qin Pan,1
Victor Tunje Jeza,1
Bing Xia,3
Jianguo Wu,2* and
Xiao-Lian Zhang1*
Department of Immunology, Hubei Province Key Laboratory of Allergy and Immune-Related Diseases, The State Key Laboratory of Virology, Wuhan University School of Medicine, Wuhan 430071, People's Republic of China,1 The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China,2 Zhongnan Hospital, Wuhan University, Wuhan 430071, People's Republic of China3
Received 10 February 2007/ Returned for modification 6 March 2007/ Accepted 31 May 2007
Attenuated Salmonella enterica serovar Typhi strains have been considered to be attractive as potential live oral delivery vector vaccines because of their ability to elicit the full array of immune responses in humans. In this study, we constructed an attenuated S. enterica serovar Typhi strain stably expressing conserved nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) by integrating the N gene into the pilV gene, which was under the control of the type IVB pilus operon promoter in S. enterica serovar Typhi. BALB/c mice were immunized with this recombinant strain through different routes: intranasally, orogastrically, intraperitoneally, and intravenously. Results showed that the intranasal route caused the highest production of specific immunoglobulin G (IgG), IgG2a, and secretory IgA, where IgG2a was imprinted as a Th1 cell bias. Moreover, this recombinant live vaccine induced significantly high levels of specific cytotoxic T-lymphocyte activities and increased gamma interferon-producing T cells compared with the parental strain. Our work provides insights into how the type IVB pilus operon promoter controlling SARS-CoV N gene expression in Salmonella might be attractive for a live-vector vaccine against SRAS-CoV infection, for it could induce mucosal, humoral, and cellular immune responses. Our work also indicates that the type IVB pilus operon promoter controlling foreign gene expression in Salmonella can elicit full immune responses by intranasal vaccination.
* Corresponding author. Mailing address for X.-L. Zhang: Department of Immunology, Wuhan University School of Medicine, 165 Donghu Road, Wuhan 430071, People's Republic of China. Phone: 86-27-87331183. Fax: 86-27-87336380. E-mail: ZhangXL65{at}whu.edu.cn. Mailing address for J. Wu: The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China. Phone: 86-27-68754979. Fax: 86-27-68754592. E-mail: wu9988{at}vip.sina.com
Published ahead of print on 27 June 2007.
F.L. and Y.F. contributed equally to this work.
Clinical and Vaccine Immunology, August 2007, p. 990-997, Vol. 14, No. 8
1071-412X/07/$08.00+0 doi:10.1128/CVI.00076-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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