Codon optimization and ubiquitin conjugation of human immunodeficiency virus-1 Tat lead to enhanced cell-mediated immune responses

Ramakrishna, Lakshmi and Krishnamurthy, Ananda Kumar and Mahalingam, Marthandan and Mohankumara, Kumarasamypet M and Ramanib, Shilpa and Siddappa, Nagadenahalli B and Ranga, Udaykumar (2004) Codon optimization and ubiquitin conjugation of human immunodeficiency virus-1 Tat lead to enhanced cell-mediated immune responses. In: Vaccine, 22 (20). pp. 2586-2598.

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Abstract

The transactivator protein, Tat, is a potential candidate for developing a vaccine against human immunodeficiency virus (HIV-1). Since Tat is not immunodominant, especially when delivered as a genetic vaccine, we expressed codon-optimized subtype-C Tat as a molecular conjugate of ubiquitin, to elicit antigen-specific cell-mediated immune responses. Immunization of mice with different ubiquitin-Tat constructs elicited a strong cellular, but not a humoral, immune response. The combination of codon-optimization and ubiquitin-mediated processing of Tat induced a Th-1 type cellular immune response that was detectable without in vitro stimulation, suggesting its potential utility for destruction of virus-infected cells via CTL-mediated lysis. Preliminary attempts at characterizing the immunodominant regions identified a novel T-helper epitope within the core domain of Tat.

Item Type:	Journal Article
Publication:	Vaccine
Publisher:	Elsevier
Additional Information:	copyright of this article belongs to Elsevier
Keywords:	HIV-1 subtype-C Tat;Molecular adjuvant;DNA vaccine
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	18 Dec 2008 09:52
Last Modified:	19 Sep 2010 04:53
URI:	http://eprints.iisc.ac.in/id/eprint/16780

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