Ra. Boykins et al., Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice, PEPTIDES, 21(12), 2000, pp. 1839-1847
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.