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Journal of Virology, July 1999, p. 5320-5325, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Immunogenicity of a Human Immunodeficiency Virus (HIV) Polytope Vaccine Containing Multiple HLA A2 HIV CD8+ Cytotoxic T-Cell Epitopes

T. Woodberry,1 J. Gardner,1 L. Mateo,1 D. Eisen,2 J. Medveczky,3 I. A. Ramshaw,3 S. A. Thomson,1 R. A. Ffrench,4 S. L. Elliott,1 H. Firat,5 F. A. Lemonnier,5 and A. Suhrbier1,*

Australian Centre for International & Tropical Health & Nutrition, Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research,1 and Infectious Diseases Unit, Royal Brisbane Hospital,2 Brisbane, and Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra,3 and Paediatric Research Laboratories, Sydney Children's Hospital, Randwick,4 Australia, and Département SIDA-Rétrovirus, Unité d'Immunite Cellulaire Antivirale, Institut Pasteur, Paris, France5

Received 14 December 1998/Accepted 18 March 1999

Compelling evidence now suggests that alpha beta CD8 cytotoxic T lymphocytes (CTL) have an important role in preventing human immunodeficiency virus (HIV) infection and/or slowing progression to AIDS. Here, we describe an HIV type 1 CTL polyepitope, or polytope, vaccine comprising seven contiguous minimal HLA A2-restricted CD8 CTL epitopes conjoined in a single artificial construct. Epitope-specific CTL lines derived from HIV-infected individuals were able to recognize every epitope within the construct, and HLA A2-transgenic mice immunized with a recombinant virus vaccine coding for the HIV polytope also generated CTL specific for different epitopes. Each epitope in the polytope construct was therefore processed and presented, illustrating the feasibility of the polytope approach for HIV vaccine design. By simultaneously inducing CTL specific for different epitopes, an HIV polytope vaccine might generate activity against multiple challenge isolates and/or preempt the formation of CTL escape mutants.


* Corresponding author. Mailing address: Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, Qld. 4029, Australia. Phone: 61-7-33620415. Fax: 61-7-33620107. E-mail: andreasS{at}qimr.edu.au.


Journal of Virology, July 1999, p. 5320-5325, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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