Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response
- PMID: 15694508
- DOI: 10.1016/j.vaccine.2004.09.037
Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response
Abstract
2F5 is one of the few broadly neutralizing monoclonal antibodies against type 1 Human Immunodeficiency Virus (HIV-1). It recognizes the amino acid sequence ELDKWAS in gp41. We have previously identified a number of immunotargeting 2F5-reactive candidate immunogens. Three of them (designated H-BT1-3) have the ELDKWAS sequence constrained at beta-turn sites within the immunoglobulin heavy chain. Two others (L-CT and L-CTx3) have the sequence attached at the C-terminus of the immunoglobulin light chain with minimal conformational constraints. In the present investigation, the H-BTs were found to bind 2F5 with up to 10-fold higher affinities than their unconstrained counterpart. When used as immunogens, immunogen-specific antibodies were induced with or without adjuvant, confirming the immunotargeting potential of these immunogen constructs. While HIV-1 gp160 cross-reactive antibodies were induced, virus neutralization was not detected. Thus, factors other than 2F5 binding affinity may have a critical role to play in the design of a 2F5-based vaccine.
Similar articles
-
Crystal structure of the complex between the F(ab)' fragment of the cross-neutralizing anti-HIV-1 antibody 2F5 and the F(ab) fragment of its anti-idiotypic antibody 3H6.J Mol Biol. 2008 Oct 17;382(4):910-9. doi: 10.1016/j.jmb.2008.07.057. Epub 2008 Jul 27. J Mol Biol. 2008. PMID: 18692506
-
Human immunodeficiency virus type 1-neutralizing monoclonal antibody 2F5 is multispecific for sequences flanking the DKW core epitope.J Mol Biol. 2004 Apr 23;338(2):311-27. doi: 10.1016/j.jmb.2004.02.051. J Mol Biol. 2004. PMID: 15066434
-
Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5: epitope conformation, antigen-recognition loop mobility, and anion-binding site.J Mol Biol. 2008 Dec 12;384(2):377-92. doi: 10.1016/j.jmb.2008.09.024. Epub 2008 Sep 18. J Mol Biol. 2008. PMID: 18824005
-
Characterization of the antibody response elicited by HIV-1 Env glycomutants in rabbits.Vaccine. 2007 Jan 5;25(3):535-46. doi: 10.1016/j.vaccine.2006.07.051. Epub 2006 Aug 7. Vaccine. 2007. PMID: 16934377
-
Interactions of HIV-1 antibodies 2F5 and 4E10 with a gp41 epitope prebound to host and viral membrane model systems.Chembiochem. 2009 Apr 17;10(6):1032-44. doi: 10.1002/cbic.200800609. Chembiochem. 2009. PMID: 19283693
Cited by
-
Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10.Proc Natl Acad Sci U S A. 2009 May 5;106(18):7385-90. doi: 10.1073/pnas.0811427106. Epub 2009 Apr 16. Proc Natl Acad Sci U S A. 2009. PMID: 19372381 Free PMC article.
-
The broadly neutralizing anti-human immunodeficiency virus type 1 4E10 monoclonal antibody is better adapted to membrane-bound epitope recognition and blocking than 2F5.J Virol. 2008 Sep;82(18):8986-96. doi: 10.1128/JVI.00846-08. Epub 2008 Jul 2. J Virol. 2008. PMID: 18596094 Free PMC article.
-
Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies.Nat Struct Mol Biol. 2014 Dec;21(12):1058-67. doi: 10.1038/nsmb.2922. Epub 2014 Nov 24. Nat Struct Mol Biol. 2014. PMID: 25420104 Free PMC article.
-
Development of prophylactic vaccines against HIV-1.Retrovirology. 2013 Jul 17;10:72. doi: 10.1186/1742-4690-10-72. Retrovirology. 2013. PMID: 23866844 Free PMC article. Review.
-
In vivo and in vitro escape from neutralizing antibodies 2G12, 2F5, and 4E10.J Virol. 2007 Aug;81(16):8793-808. doi: 10.1128/JVI.00598-07. Epub 2007 Jun 13. J Virol. 2007. PMID: 17567707 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
