This article is part of the supplement: AIDS Vaccine 2009
Poster presentation
P19-28. The V3 region of HIV-1: from NMR to vaccine design
Retrovirology 2009, 6(Suppl 3):P348 doi:10.1186/1742-4690-6-S3-P348
The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/6/S3/P348
| Published: | 22 October 2009 |
© 2009 Moseri et al; licensee BioMed Central Ltd.
Background
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.
Methods
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.
Results
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.
Conclusion
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.