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Journal of Virology, September 2007, p. 10009-10016, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00489-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Induction of Potent CD8+ T-Cell Responses by Novel Biodegradable Nanoparticles Carrying Human Immunodeficiency Virus Type 1 gp120{triangledown}

Xin Wang,1,3 Tomofumi Uto,1,3 Takami Akagi,2,3 Mitsuru Akashi,2,3 and Masanori Baba1,3*

Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544,1 Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871,2 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo 150-0002, Japan3

Received 8 March 2007/ Accepted 27 June 2007

The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly({gamma}-glutamic acid) ({gamma}-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8+ T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8+ T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8+ T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8+ T cells rapidly expanded with boosting with the same immunogen. In addition, {gamma}-PGA NPs were found to be a much stronger inducer of antigen-specific CD8+ T-cell responses than nonbiodegradable polystyrene NPs. Thus, {gamma}-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses.


* Corresponding author. Mailing address: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8544, Japan. Phone: 81 99-275-5930. Fax: 81 99-275-5932. E-mail: m-baba{at}vanilla.ocn.ne.jp

{triangledown} Published ahead of print on 3 July 2007.


Journal of Virology, September 2007, p. 10009-10016, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00489-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.