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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

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(-glutamic acid) (-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, -PGA NPs were found to be a much stronger inducer of antigen-specific CD8⁺ T-cell responses than nonbiodegradable polystyrene NPs. Thus, -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.

Published ahead of print on 3 July 2007.