Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice

We report here a novel, highly immunogenic synthetic, multiple-peptide conj ugate comprising functional domains Tat(21-40) and Tat(53-68) from HIV-I gr oup M plus Tat(9-20) from HIV-I group O of the HIV-Tat protein (HIV-1-Tat-M PC). Vaccination of mice with HIV-I-Tat-MPC induced an effective immune res ponse to all three functional domains. The anti-HTV-1-Tat-MPC antibodies ef ficiently inhibited Tar-induced viral activation in monocytes infected with HIVBa-L as well as with various clinical HIV-l isolates, and reduced Tat-m ediated cytopathicity in infected cells by 60-75%. Our results indicate tha t anti-HIV-l-Tat-MPC antibodies inhibit viral pathogenesis, possibly by blo cking functional determinants of Tar and disrupting autocrine and paracrine actions of secreted Tat protein. This epitope-specific, synthetic Tat cons truct may, therefore, provide a subunit AIDS vaccine candidate for inducing an effective immunoprophylaxis response to reduce progression of HIV infec tion. (C) 2000 Elsevier Science Inc. All rights reserved.