This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Takagi, A.
Right arrow Articles by Akatsuka, T.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takagi, A.
Right arrow Articles by Akatsuka, T.

Next Article 

Clinical and Vaccine Immunology, October 2009, p. 1383-1392, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00116-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Highly Efficient Antiviral CD8+ T-Cell Induction by Peptides Coupled to the Surfaces of Liposomes{triangledown}

Akira Takagi,1 Masanori Matsui,1 Satoshi Ohno,1 Hongying Duan,1 Osamu Moriya,1 Nobuharu Kobayashi,1 Hiroshi Oda,2 Masahito Mori,2 Akiharu Kobayashi,2 Maiko Taneichi,3 Tetsuya Uchida,3 and Toshitaka Akatsuka1*

Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-Cho, Iruma-Gun, Saitama 350-0495, Japan,1 Drug Delivery System Development Division, Nippon Oil and Fat Corporation, 4-20-3 Ebisu, Shibuya-Ku, Tokyo 150-6019, Japan,2 Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan3

Received 15 March 2009/ Returned for modification 28 May 2009/ Accepted 4 August 2009

In previous studies, we have demonstrated that liposomes with differential lipid components display differential adjuvant effects when antigens (Ags) are chemically coupled to their surfaces. When ovalbumin was coupled to liposomes made by using unsaturated fatty acids, it was found to be presented not only to CD4+ T cells but also to CD8+ T cells and induced cytotoxic T lymphocytes (CTLs) which effectively eradicated the tumor from mice. In this study, we coupled liposomes to immunodominant CTL epitope peptides derived from lymphocytic choriomeningitis virus (LCMV) and evaluated its potency as an antiviral vaccine. The intramuscular immunization of mice with the peptide-liposome conjugates along with CpG resulted in the efficient induction of antiviral CD8+ T-cell responses which conferred complete protection against not only LCMV Armstrong but also a highly virulent mutant strain, clone 13, that establishes persistent infections in immunocompetent mice. The intranasal vaccination induced mucosal immunity effective enough to protect mice from the virus challenge via the same route. Complete protection was achieved in mice even when the Ag dose was reduced to as low as 280 ng of liposomal peptide. This form of vaccination with a single CTL epitope induced Ag-specific memory CD8+ T cells in the absence of CD4+ T-cell help, which could be shown by the complete protection of CD4-knockout mice in 10 weeks as well as by the analysis of recall responses. Thus, surface-linked liposomal peptide might have a potential advantage for the induction of antiviral immunity.

* Corresponding author. Mailing address: Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan. Phone: 81-49-276-1165. Fax: 81-49-295-9107. E-mail: akatsuka{at}saitama-med.ac.jp

{triangledown} Published ahead of print on 12 August 2009.

Clinical and Vaccine Immunology, October 2009, p. 1383-1392, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00116-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»