This article is part of the supplement: AIDS Vaccine 2012

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Design of an HIV Env antigen that binds with high affinity to antibodies against linear, conformational and broadly neutralizing epitopes within V1/V2

L Liao1*, M Bonsignori1, K Hwang1, AM Moody1, R Park1, S Crawford1, H Chen1, TL Jeffries1, M Cooper1, X Lu1, R De1, N Karasavvas2, S Rerks-Ngarm3, S Nitayaphan4, J Kaewkungwal5, S Tovanabutra2, P Pitisuttithum6, J Tartaglia7, F Sinangil8, J Kim2, NL Michael2, GD Tomaras1, Z Yang9, K Dai9, M Pancera9, GJ Nabel9, JR Mascola9, PD Kwong9, A Pinter10, S Zolla-Pazner11, MS Alam1 and BF Haynes1

  • * Corresponding author: L Liao

Author Affiliations

1 Duke University Medical Center, Durham, NC, USA

2 U.S. MHRP, Walter Reed Army Institute of Research, Silver Spring, MD, USA

3 Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand

4 Department of Retrovirology, US Army Medical Component, AFRIMS, Bangkok, Thailand

5 BIOPHICS, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

6 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

7 Department of Research and Development, Sanofi Pasteur, Swiftwater, PA, USA

8 Global Solutions for Infectious Diseases, South San Francisco, CA, USA

9 Vaccine Research Center/NIH, Bethesda, MD, USA

10 Public Health Research Institute Center, New Jersey Medical School, Newark, NJ, USA

11 Veterans Affairs New York Harbor Healthcare System, Manhattan Campus, New York, NY, USA

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Retrovirology 2012, 9(Suppl 2):O31  doi:10.1186/1742-4690-9-S2-O31

The electronic version of this article is the complete one and can be found online at:

Published:13 September 2012

© 2012 Liao et al; licensee BioMed Central Ltd.

This is an Open Access article 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.


The RV144 HIV-1 vaccine trial showed protection from HIV-1 acquisition with vaccine efficacy of 31.2%. Study of the immune correlates demonstrated an inverse association of V1/V2 antibodies with infection risk. A key task for HIV-1 vaccine development is to improve the level of efficacy seen in the RV144 trial with subsequent vaccine designs.


E.A244 V1/V2 Env tags contains an N-terminal Ig leader sequence and C-terminal Avi- and His6-tags linked to the V1/V2 domain, was expressed in 293F cells and purified by nickel column. Binding of Tier 1 neutralizing mAb CH58 from RV144 vaccinees, V2 conformational mAb 697D and broadly neutralizing antibodies (bnAb) CH01 and PG9/PG16 to 33 HIV-1 gp140/gp120s and 12 HIV-1 V1/V2 scaffold Envs was tested by ELISA and surface plasmon resonance.


Among 45 HIV-1/SIV Envs tested, E.A244 V1/V2 tags and E.A244 gp120Δ11 Env were the only Env antigens recognized by all three types of mAbs: CH58, 697D, and bnAbs CH01, and PG9/PG16. E.A244 V1/V2 tag bound CH58 with a Kd of 0.33 nM and 697D with a Kd of 117 nM. Although PG9 preferentially recognizes trimers, PG9 bound well to both E.A244 gp120Δ11 (Kd = 47.3) and E.A244 V1/V2 tags (Kd = 83.3 nM). BnAb CH01 bound V1/V2 tags as well (Kd = 334 nM). E.A244 V1/V2 Env tags was also recognized by the unmutated ancestor antibodies (UAs) of CH58 with ELISA EC50 = 4.9 nM and CH01 with EC50 = ~1μM. E.A244 V1/V2 tags and AE.gp70 V1/V2 scaffold were the best recombinant Envs for detection of plasma V1/V2 antibodies in RV144 vaccinees.


Recombinant E.A244 V1/V2 Env tags Env expresses linear as well as conformational determinants recognized by V1/V2 mAbs and some of their UAs. This V1/V2 construct is a candidate immunogen to target RUAs and intermediate ancestors of V1/V2 antibodies to drive their induction.