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

Lakshmi Ramakrishna, Krishnamurthy Kumar Anand, Marthandan Mahalingam, Kumarasamypet M. Mohankumar, Shilpa Ramani, Nagadenahalli B. Siddappa, Udaykumar Ranga

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2586-2598
Number of pages13
JournalVaccine
Volume22
Issue number20
DOIs
StatePublished - Jun 30 2004

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Keywords

  • DNA vaccine
  • HIV-1 subtype-C Tat
  • Molecular adjuvant

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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