TY - JOUR
T1 - Codon optimization and ubiquitin conjugation of human immunodeficiency virus-1 Tat lead to enhanced cell-mediated immune responses
AU - Ramakrishna, Lakshmi
AU - Anand, Krishnamurthy Kumar
AU - Mahalingam, Marthandan
AU - Mohankumar, Kumarasamypet M.
AU - Ramani, Shilpa
AU - Siddappa, Nagadenahalli B.
AU - Ranga, Udaykumar
N1 - Funding Information:
This work was supported by a grant (BT/MED/HIV/05/99) from The Department of BioTechnology, Government of India to U.R. L.R. K.K.A., R.S. and N.B.S. are recipients of research fellowships of the Council for Scientific and Industrial Research of The Government of India. We wish to thank professor Vijaya S. for helpful comments. A number of reagents used in this study were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH, USA and The Centralized Facility for AIDS Reagents, National Institute for Biological Standards and Control, UNAIDS.
PY - 2004/6/30
Y1 - 2004/6/30
N2 - 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.
AB - 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.
KW - DNA vaccine
KW - HIV-1 subtype-C Tat
KW - Molecular adjuvant
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U2 - 10.1016/j.vaccine.2003.12.007
DO - 10.1016/j.vaccine.2003.12.007
M3 - Article
C2 - 15193384
AN - SCOPUS:2942620236
VL - 22
SP - 2586
EP - 2598
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 20
ER -