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Journal of Virology, December 2005, p. 14822-14833, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14822-14833.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Induction of Human Immunodeficiency Virus Type 1-Specific T Cells by a Bluetongue Virus Tubule-Vectored Vaccine Prime-Recombinant Modified Virus Ankara Boost Regimen

Natasha Larke,1 Aileen Murphy,2 Christoph Wirblich,2 Denise Teoh,1 Marie J. Estcourt,1,{dagger} Andrew J. McMichael,1 Polly Roy,2 and Tomás Hanke1*

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, University of Oxford, Oxford OX3 9DS,1 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom2

Received 24 June 2005/ Accepted 11 September 2005

In the absence of strategies for reliable induction of antibodies broadly neutralizing human immunodeficiency virus type 1 (HIV-1), vaccine efforts have shifted toward the induction of cell-mediated immunity. Here we describe the construction and immunogenicity of novel T-cell vaccine NS1.HIVA, which delivers the HIV-1 clade A consensus-derived immunogen HIVA on the surface of tubular structures spontaneously formed by protein NS1 of bluetongue virus. We demonstrated that NS1 tubules can accommodate a protein as large as 527 amino acids without losing their self-assembly capability. When injected into BALB/c mice by several routes, chimeric NS1.HIVA tubules induced HIV-1-specific major histocompatibility complex class I-restricted T cells. These could be boosted by modified virus Ankara expressing the same immunogen and generate a memory capable of gamma interferon (IFN-{gamma}) production, proliferation, and lysis of sensitized target cells. Induced memory T cells readily produced IFN-{gamma} 230 days postimmunization, and upon a surrogate virus challenge, NS1.HIVA vaccine alone decreased the vaccinia virus vv.HIVA load in ovaries by 2 orders of magnitude 280 days after immunization. Thus, because of its T-cell immunogenicity and antigenic simplicity, the NS1 delivery system could serve as a priming agent for heterologous prime-boost vaccination regimens. Its usefulness in primates, including humans, remains to be determined.

* Corresponding author. Mailing address: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, United Kingdom. Phone: 44 1865 222355. Fax: 44 1865 222502. E-mail: tomas.hanke{at}imm.ox.ac.uk.

{dagger} Present address: Department of Pathology and Molecular Medicine, Institute for Molecular Medicine and Health, McMaster University, MDCL 4074, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.

Journal of Virology, December 2005, p. 14822-14833, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14822-14833.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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