Barouch, Dan Hung

Chen, Bing

Cheung, A

Kovacs, James Monroe

Miller, CA

Nkolola, Joseph Patrick

Peng, H

Perry, J

Seaman, Michael S.

Retrovirology

Harvard University - DASH 

 HIV-1 Envelope Trimer Elicits Higher Neutralizing AntibodyResponses than Monomeric Gp120  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Kovacs, J. M., J. P. Nkolola, H. Peng, A. Cheung, J. Perry, C. A.Miller, M. S. Seaman, D. Barouch, and B. Chen. 2012. HIV-1envelope trimer elicits higher neutralizing antibody responsesthan monomeric gp120. Retrovirology 9(Suppl 2): O62.Published Version doi:10.1186/1742-4690-9-S2-O62Accessed February 19, 2015 10:50:14 AM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10536045Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAAORAL PRESENTATION Open AccessHIV-1 envelope trimer elicits higher neutralizingantibody responses than monomeric gp120JM Kovacs1*, JP Nkolola2, H Peng3, A Cheung4, J Perry4, CA Miller4, MS Seaman4, D Barouch2, B Chen1From AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundHIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike onthe virion surface is a trimer, but trimeric gp140 and mono-meric gp120 are currently believed to induce comparableimmune responses. Indeed, most studies on the immuno-genicity of HIV-1 envelope oligomers have revealed onlymarginal improvement over monomers. We report herethat stable and homogenous envelope trimers with charac-teristics expected for the native viral spikes are substantiallysuperior at eliciting neutralizing antibodies in guinea pigs.MethodsStable envelope gp140 trimer derived from clinical isolatesequences were stabilized with the T4-fibritin C-terminaltrimerization tag and produced in stablely transfected293T cells. Characterization of Env trimers was performedby Western blotting, size-exclusion chromatography(SEC), analytical-ultra centrifugation (AUC), multi-anglelight scattering (MALS) and surface plasmon resonance(SPR). Guinea pigs were immunized six times with 100 µgof protein trimer or monomer in CpG/Emulsigen adju-vants. Antibody responses were determined by ELISA andTZM.bl neutralizing antibody assays.ResultsHomogeneous trimer and monomer preparations exhib-ited high purity as measured by SEC and SDS-PAGE.AUC and MALS analyses revealed expected molecularweight for both trimer and monomer. SPR analysesrevealed expected binding with CD4 and multiple broadlyneutralizing antibodies. These trimers have markedly dif-ferent antigenic properties than those of monomericgp120s derived from the same sequences. They inducepotent, cross-clade neutralizing antibody responses withtiters substantially higher than those elicited by the corre-sponding gp120 monomers for a diverse set of both tier 1and tier 2 viruses.ConclusionWe have demonstrated the importance of generating high-quality envelope trimers for antigenic and immunogenicstudies; furthermore these results highlight the immunolo-gic differences between monomers and high-quality envel-ope trimers, illustrating important implications for HIV-1vaccine development and immunogen selection in largeclinical trials.Author details1Harvard Medical School and Children’s Hospital Boston, Boston, MA, USA.2Beth Israel Deaconess Medical Center and Ragon Institute, Boston, MA, USA.3Children’s Hospital Boston, Boston, MA, USA.4Beth Israel Deaconess MedicalCenter, Boston, MA, USA.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-O62Cite this article as: Kovacs et al.: HIV-1 envelope trimer elicits higherneutralizing antibody responses than monomeric gp120. Retrovirology2012 9(Suppl 2):O62.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color ﬁgure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit 1Harvard Medical School and Children’s Hospital Boston, Boston, MA, USAFull list of author information is available at the end of the articleKovacs et al. Retrovirology 2012, 9(Suppl 2):O62http://www.retrovirology.com/content/9/S2/O62© 2012 Kovacs et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

HIV-1 Envelope Trimer Elicits Higher Neutralizing Antibody Responses than Monomeric Gp120

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HIV-1 Envelope Trimer Elicits Higher Neutralizing Antibody Responses than Monomeric Gp120

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