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Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice |
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| Authors: | Boykins R A Ardans J A Wahl L M Lal R B Yamada K M Dhawan S |
| Affiliation: | a Laboratory of Parasitic Biology and Biochemistry, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA b Immunopathology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA c Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA d Immunopathogenesis Laboratory, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA e Immunopathogenesis Section, Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA |
| Abstract: | We report here a novel, highly immunogenic synthetic, multiple-peptide conjugate comprising functional domains Tat21–40 and Tat53–68 from HIV-1 group M plus Tat9–20 from HIV-1 group O of the HIV-Tat protein (HIV-1-Tat-MPC). Vaccination of mice with HIV-1-Tat-MPC induced an effective immune response to all three functional domains. The anti-HIV-1-Tat-MPC antibodies efficiently inhibited Tat-induced viral activation in monocytes infected with HIVBa-L as well as with various clinical HIV-1 isolates, and reduced Tat-mediated cytopathicity in infected cells by 60–75%. Our results indicate that anti-HIV-1-Tat-MPC antibodies inhibit viral pathogenesis, possibly by blocking functional determinants of Tat and disrupting autocrine and paracrine actions of secreted Tat protein. This epitope-specific, synthetic Tat construct may, therefore, provide a subunit AIDS vaccine candidate for inducing an effective immunoprophylaxis response to reduce progression of HIV infection. |
| Keywords: | Monocytes Macrophages HIV-1-Tat HIV AIDS Pathogenesis Vaccine |
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