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Volume 6 Supplement 3

AIDS Vaccine 2009

P19-28. The V3 region of HIV-1: from NMR to vaccine design


The V3 loop is one of the few epitopes to which broadly neutralizing antibody response can be directed. The most potent and most broadly neutralizing anti-V3 antibody to date is the human monoclonal antibody 447-52D. Using NMR spectroscopy, we studied the conformation of several V3 peptides in complex with 447-52D. The flexible V3 peptides were found to adopt a β-hairpin conformation when bound to this antibody. Using disulfide bonds we constrained V3 peptides to adopt a conformation similar to those of V3 peptides bound to 447-52D.


Two cyclic peptides, P2 and P3, based on the consensus sequence of clade-B R5 viruses were synthesized in the form of a C4-V3 construct and compared with the linear peptide (P1). The peptide P2 was constrained by a disulfide bond at positions T303C/I323C and included the entire 447-52D epitope (R304-E322); the peptide P3 was constrained closer to the GPGR turn at positions K305C/T320C. Sera of rabbits immunized with these three peptides were tested for the ability to neutralize a panel of HIV-1 isolates.


The peptide constrained at position T303C/I323C (P2) elicited a more potent HIV-1 neutralizing response in comparison with the linear P1 or the constrained peptide P3. All 4 sera of rabbits immunized with P2 neutralized 5 out of the 7 strains tested. For the SF162 strain, which differed by three mutations from the immunizing V3-peptide, 50% neutralization was achieved with average titers greater than 1,580, at least 20-fold and 40-fold better than the linear peptide (P1) and the other constrained peptide (P3) immune-sera, respectively.


We have demonstrated that constrained V3 peptides can elicit strong HIV-1 neutralizing response that is considerably more potent in comparison with linear peptide immune-sera given that the constraint is optimally located within the V3 epitope to include the entire V3 epitope recognized by the 447-52D antibody.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Moseri, A., Naider, F. & Anglister, J. P19-28. The V3 region of HIV-1: from NMR to vaccine design. Retrovirology 6 (Suppl 3), P348 (2009).

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