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Journal of Virology, March 2009, p. 2201-2215, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.02256-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Expanded Breadth of the T-Cell Response to Mosaic Human Immunodeficiency Virus Type 1 Envelope DNA Vaccination{triangledown} ,{dagger}

Wing-Pui Kong,1 Lan Wu,1 Timothy C. Wallstrom,2 Will Fischer,2 Zhi-Yong Yang,1 Sung-Youl Ko,1 Norman L. Letvin,3 Barton F. Haynes,4 Beatrice H. Hahn,5 Bette Korber,2,6 and Gary J. Nabel1*

Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005,1 Los Alamos National Laboratory, MS K710, T-10, Los Alamos, New Mexico 87545,2 Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P.O. Box 15732, Boston, Massachusetts 02115,3 Duke Human Vaccine Institute, Duke University Medical Center, MSRBII Building, Room 4085, P.O. Box 103020, Research Drive, Durham, North Carolina 27710,4 Department of Medicine, University of Alabama at Birmingham, Kaul 816, 720 20th Street South, Birmingham, Alabama 35294,5 Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, New Mexico 875016

Received 27 October 2008/ Accepted 12 December 2008

An effective AIDS vaccine must control highly diverse circulating strains of human immunodeficiency virus type 1 (HIV-1). Among HIV-1 gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV-1 Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential T-cell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. One-, two-, and three-mosaic sets that increased theoretical epitope coverage were developed. The breadth and magnitude of T-cell immunity stimulated by these vaccines were compared to those for natural strain Envs; additional comparisons were performed on mutant Envs, including gp160 or gp145 with or without V regions and gp41 deletions. Among them, the two- or three-mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the three-mosaic set elicited responses to an average of eight peptide pools, compared to two pools for a set of three natural Envs. Synthetic mosaic HIV-1 antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T-cell-based HIV-1 vaccines.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005. Phone: (301) 496-1852. Fax: (301) 480-0274. E-mail: gnabel{at}nih.gov

{triangledown} Published ahead of print on 24 December 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, March 2009, p. 2201-2215, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.02256-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Korber, B. T., Letvin, N. L., Haynes, B. F. (2009). T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with a Thousand Faces. J. Virol. 83: 8300-8314 [Full Text]  


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